ID NLRP1_HUMAN Reviewed; 1473 AA. AC Q9C000; E9PE50; I6L9D9; Q9BZZ8; Q9BZZ9; Q9H5Z7; Q9H5Z8; Q9HAV8; Q9UFT4; AC Q9Y2E0; DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 1. DT 27-MAR-2024, entry version 231. DE RecName: Full=NACHT, LRR and PYD domains-containing protein 1 {ECO:0000305}; DE EC=3.4.-.- {ECO:0000269|PubMed:22087307}; DE EC=3.6.4.- {ECO:0000269|PubMed:33243852}; DE AltName: Full=Caspase recruitment domain-containing protein 7; DE AltName: Full=Death effector filament-forming ced-4-like apoptosis protein {ECO:0000303|PubMed:11076957}; DE AltName: Full=Nucleotide-binding domain and caspase recruitment domain; DE Contains: DE RecName: Full=NACHT, LRR and PYD domains-containing protein 1, C-terminus {ECO:0000305}; DE Short=NLRP1-CT {ECO:0000303|PubMed:33420033}; DE Contains: DE RecName: Full=NACHT, LRR and PYD domains-containing protein 1, N-terminus {ECO:0000305}; DE Short=NLRP1-NT {ECO:0000303|PubMed:33420033}; GN Name=NLRP1 {ECO:0000303|PubMed:22665479, ECO:0000312|HGNC:HGNC:14374}; GN Synonyms=CARD7, DEFCAP {ECO:0000303|PubMed:11076957}, KIAA0926 GN {ECO:0000303|PubMed:10231032}, NAC {ECO:0000303|PubMed:11113115}, GN NALP1 {ECO:0000303|PubMed:15285719}; 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 [MRNA] (ISOFORM 2), AND VARIANTS HIS-155; SER-246; RP MET-878; VAL-1119; VAL-1184; LEU-1241 AND CYS-1366. RX PubMed=11270363; DOI=10.1038/sj.cdd.4400774; RA Bertin J., DiStefano P.S.; RT "The PYRIN domain: a novel motif found in apoptosis and inflammation RT proteins."; RL Cell Death Differ. 7:1273-1274(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=11250163; DOI=10.1016/s0960-9822(01)00056-2; RA Martinon F., Hofmann K., Tschopp J.; RT "The pyrin domain: a possible member of the death domain-fold family RT implicated in apoptosis and inflammation."; RL Curr. Biol. 11:R118-R120(2001). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND MUTAGENESIS OF LYS-340. RC TISSUE=Erythroleukemia; RX PubMed=11076957; DOI=10.1074/jbc.m009853200; RA Hlaing T., Guo R.-F., Dilley K.A., Loussia J.M., Morrish T.A., Shi M.M., RA Vincenz C., Ward P.A.; RT "Molecular cloning and characterization of DEFCAP-L and -S, two isoforms of RT a novel member of the mammalian Ced-4 family of apoptosis proteins."; RL J. Biol. Chem. 276:9230-9238(2001). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), FUNCTION, TISSUE RP SPECIFICITY, AND DEVELOPMENTAL STAGE. RC TISSUE=T-cell; RX PubMed=11113115; DOI=10.1074/jbc.m006309200; RA Chu Z.-L., Pio F., Xie Z., Welsh K., Krajewska M., Krajewski S., Godzik A., RA Reed J.C.; RT "A novel enhancer of the Apaf1 apoptosome involved in cytochrome c- RT dependent caspase activation and apoptosis."; RL J. Biol. Chem. 276:9239-9245(2001). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=10231032; DOI=10.1093/dnares/6.1.63; RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., RA Tanaka A., Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XIII. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 6:63-70(1999). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). RC TISSUE=Blood; 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 [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 282-1473 (ISOFORM 1), AND VARIANT RP VAL-1184. RC TISSUE=Uterus; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 508-1473. 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 [10] RP PROTEIN SEQUENCE OF 1213-1224, FUNCTION, INTERACTION WITH PYCARD, RP INVOLVEMENT IN INFLAMMASOME COMPLEX, AUTOCATALYTIC CLEAVAGE, SUBCELLULAR RP LOCATION, CHARACTERIZATION OF VARIANTS VAL-1119 AND VAL-1184, AND RP MUTAGENESIS OF HIS-1168; HIS-1186; SER-1211; PHE-1212; SER-1213; PRO-1214 RP AND HIS-1249. RX PubMed=22665479; DOI=10.1074/jbc.m112.378323; RA Finger J.N., Lich J.D., Dare L.C., Cook M.N., Brown K.K., Duraiswami C., RA Bertin J.J., Bertin J., Gough P.J.; RT "Autolytic proteolysis within the function to find domain (FIIND) is RT required for NLRP1 inflammasome activity."; RL J. Biol. Chem. 287:25030-25037(2012). RN [11] RP ERRATUM OF PUBMED:22665479. RA Finger J.N., Lich J.D., Dare L.C., Cook M.N., Brown K.K., Duraiswami C., RA Bertin J.J., Bertin J., Gough P.J.; RL J. Biol. Chem. 287:31456-31456(2012). RN [12] RP FUNCTION, INTERACTION WITH CASP1; CASP5 AND PYCARD, AUTOINHIBITION, AND RP IDENTIFICATION IN INFLAMMASOME COMPLEX. RX PubMed=12191486; DOI=10.1016/s1097-2765(02)00599-3; RA Martinon F., Burns K., Tschopp J.; RT "The inflammasome: a molecular platform triggering activation of RT inflammatory caspases and processing of proIL-beta."; RL Mol. Cell 10:417-426(2002). RN [13] RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=15285719; DOI=10.1042/bj20040867; RA Sanz C., Calasanz M.J., Andreu E., Richard C., Prosper F., RA Fernandez-Luna J.L.; RT "NALP1 is a transcriptional target for cAMP-response-element-binding RT protein (CREB) in myeloid leukaemia cells."; RL Biochem. J. 384:281-286(2004). RN [14] RP FUNCTION, AND MUTAGENESIS OF 339-GLY-LYS-340. RX PubMed=15212762; DOI=10.1016/j.cellsig.2004.02.006; RA Liu F., Lo C.F., Ning X., Kajkowski E.M., Jin M., Chiriac C., Gonzales C., RA Naureckiene S., Lock Y.-W., Pong K., Zaleska M.M., Jacobsen J.S., RA Silverman S., Ozenberger B.A.; RT "Expression of NALP1 in cerebellar granule neurons stimulates apoptosis."; RL Cell. Signal. 16:1013-1021(2004). RN [15] RP FUNCTION, INTERACTION WITH BCL2; BCL2L1; CASP5 AND PYCARD, SUBCELLULAR RP LOCATION, AND ACTIVATION BY MDP. RX PubMed=17418785; DOI=10.1016/j.cell.2007.01.045; RA Bruey J.M., Bruey-Sedano N., Luciano F., Zhai D., Balpai R., Xu C., RA Kress C.L., Bailly-Maitre B., Li X., Osterman A., Matsuzawa S., RA Terskikh A.V., Faustin B., Reed J.C.; RT "Bcl-2 and Bcl-XL regulate proinflammatory caspase-1 activation by RT interaction with NALP1."; RL Cell 129:45-56(2007). RN [16] 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 [17] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. 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 [18] RP FUNCTION, INTERACTION WITH CASP1, AUTOINHIBITION, HOMOMERIZATION, AND RP ACTIVATION BY MDP. RX PubMed=17349957; DOI=10.1016/j.molcel.2007.01.032; RA Faustin B., Lartigue L., Bruey J.-M., Luciano F., Sergienko E., RA Bailly-Maitre B., Volkmann N., Hanein D., Rouiller I., Reed J.C.; RT "Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1 RT activation."; RL Mol. Cell 25:713-724(2007). RN [19] RP FUNCTION, INTERACTION WITH NOD2, AND ACTIVATION BY MDP. RX PubMed=18511561; DOI=10.1073/pnas.0802726105; RA Hsu L.C., Ali S.R., McGillivray S., Tseng P.H., Mariathasan S., Humke E.W., RA Eckmann L., Powell J.J., Nizet V., Dixit V.M., Karin M.; RT "A NOD2-NALP1 complex mediates caspase-1-dependent IL-1beta secretion in RT response to Bacillus anthracis infection and muramyl dipeptide."; RL Proc. Natl. Acad. Sci. U.S.A. 105:7803-7808(2008). RN [20] RP REVIEW. RX PubMed=32558991; DOI=10.1111/imr.12884; RA Taabazuing C.Y., Griswold A.R., Bachovchin D.A.; RT "The NLRP1 and CARD8 inflammasomes."; RL Immunol. Rev. 297:13-25(2020). RN [21] RP LACK OF ACTIVATION BY ANTHRAX LETHAL TOXIN, AND ACTIVITY REGULATION. RX PubMed=19651869; DOI=10.1128/iai.00276-09; RA Liao K.C., Mogridge J.; RT "Expression of Nlrp1b inflammasome components in human fibroblasts confers RT susceptibility to anthrax lethal toxin."; RL Infect. Immun. 77:4455-4462(2009). RN [22] RP FUNCTION, AUTOCATALYTIC CLEAVAGE, AND MUTAGENESIS OF SER-1213. RX PubMed=22087307; DOI=10.1371/journal.pone.0027396; RA D'Osualdo A., Weichenberger C.X., Wagner R.N., Godzik A., Wooley J., RA Reed J.C.; RT "CARD8 and NLRP1 undergo autoproteolytic processing through a ZU5-like RT domain."; RL PLoS ONE 6:E27396-E27396(2011). RN [23] 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 [24] RP INTERACTION WITH VACCINIA VIRUS PROTEIN F1. RX PubMed=16439990; DOI=10.1038/sj.cdd.4401853; RA Postigo A., Cross J.R., Downward J., Way M.; RT "Interaction of F1L with the BH3 domain of Bak is responsible for RT inhibiting vaccinia-induced apoptosis."; RL Cell Death Differ. 13:1651-1662(2006). RN [25] RP INDUCTION. RX PubMed=24439873; DOI=10.1016/j.ijcard.2013.12.201; RA Bleda S., de Haro J., Varela C., Esparza L., Ferruelo A., Acin F.; RT "NLRP1 inflammasome, and not NLRP3, is the key in the shift to RT proinflammatory state on endothelial cells in peripheral arterial RT disease."; RL Int. J. Cardiol. 172:E282-E284(2014). RN [26] 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 [27] RP FUNCTION. RX PubMed=25562666; DOI=10.1038/jid.2014.551; RA Sollberger G., Strittmatter G.E., Grossi S., Garstkiewicz M., RA Auf dem Keller U., French L.E., Beer H.D.; RT "Caspase-1 activity is required for UVB-induced apoptosis of human RT keratinocytes."; RL J. Invest. Dermatol. 135:1395-1404(2015). RN [28] RP INDUCTION BY ATF4. RX PubMed=26086088; DOI=10.1371/journal.pone.0130635; RA D'Osualdo A., Anania V.G., Yu K., Lill J.R., Kaufman R.J., Matsuzawa S., RA Reed J.C.; RT "Transcription factor ATF4 induces NLRP1 inflammasome expression during RT endoplasmic reticulum stress."; RL PLoS ONE 10:E0130635-E0130635(2015). RN [29] RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND CHARACTERIZATION RP OF VARIANT AIADK ARG-1214. RX PubMed=30291141; DOI=10.1074/jbc.ra118.004350; RA Zhong F.L., Robinson K., Teo D.E.T., Tan K.Y., Lim C., Harapas C.R., RA Yu C.H., Xie W.H., Sobota R.M., Au V.B., Hopkins R., D'Osualdo A., RA Reed J.C., Connolly J.E., Masters S.L., Reversade B.; RT "Human DPP9 represses NLRP1 inflammasome and protects against RT autoinflammatory diseases via both peptidase activity and FIIND domain RT binding."; RL J. Biol. Chem. 293:18864-18878(2018). RN [30] RP FUNCTION. RX PubMed=30096351; DOI=10.1016/j.jid.2018.07.016; RA Fenini G., Grossi S., Contassot E., Biedermann T., Reichmann E., RA French L.E., Beer H.D.; RT "Genome Editing of Human Primary Keratinocytes by CRISPR/Cas9 Reveals an RT Essential Role of the NLRP1 Inflammasome in UVB Sensing."; RL J. Invest. Dermatol. 138:2644-2652(2018). RN [31] RP INTERACTION WITH DPP8 AND DPP9, ACTIVITY REGULATION, AND MUTAGENESIS OF RP SER-1213. RX PubMed=31525884; DOI=10.1021/acschembio.9b00462; RA Griswold A.R., Ball D.P., Bhattacharjee A., Chui A.J., Rao S.D., RA Taabazuing C.Y., Bachovchin D.A.; RT "DPP9's enzymatic activity and not its binding to CARD8 inhibits RT inflammasome activation."; RL ACS Chem. Biol. 14:2424-2429(2019). RN [32] RP FUNCTION, PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF SER-1213. RX PubMed=32051255; DOI=10.26508/lsa.202000664; RA Ball D.P., Taabazuing C.Y., Griswold A.R., Orth E.L., Rao S.D., RA Kotliar I.B., Vostal L.E., Johnson D.C., Bachovchin D.A.; RT "Caspase-1 interdomain linker cleavage is required for pyroptosis."; RL Life. Sci Alliance 3:0-0(2020). RN [33] RP FUNCTION, ACTIVITY REGULATION, DOMAIN, MUTAGENESIS OF SER-1213, RP DNA-BINDING, RNA-BINDING, AND CATALYTIC ACTIVITY. RX PubMed=33243852; DOI=10.1126/science.abd0811; RA Bauernfried S., Scherr M.J., Pichlmair A., Duderstadt K.E., Hornung V.; RT "Human NLRP1 is a sensor for double-stranded RNA."; RL Science 0:0-0(2020). RN [34] RP FUNCTION. RX PubMed=33852854; DOI=10.1016/j.celrep.2021.108998; RA Zhou B., Abbott D.W.; RT "Gasdermin E permits interleukin-1 beta release in distinct sublytic and RT pyroptotic phases."; RL Cell Rep. 35:108998-108998(2021). RN [35] RP FUNCTION, ACTIVITY REGULATION, PROTEOLYTIC CLEAVAGE (MICROBIAL INFECTION), RP AND MUTAGENESIS OF GLY-130. RX PubMed=33410748; DOI=10.7554/elife.60609; RA Tsu B.V., Beierschmitt C., Ryan A.P., Agarwal R., Mitchell P.S., RA Daugherty M.D.; RT "Diverse viral proteases activate the NLRP1 inflammasome."; RL Elife 10:0-0(2021). RN [36] RP FUNCTION, ACTIVITY REGULATION, PROTEOLYTIC CLEAVAGE (MICROBIAL INFECTION), RP AND MUTAGENESIS OF GLN-333. RX PubMed=35594856; DOI=10.1016/j.molcel.2022.04.033; RG COVID Human Genetic Effort; RA Planes R., Pinilla M., Santoni K., Hessel A., Passemar C., Lay K., RA Paillette P., Valadao A.C., Robinson K.S., Bastard P., Lam N., Fadrique R., RA Rossi I., Pericat D., Bagayoko S., Leon-Icaza S.A., Rombouts Y., RA Perouzel E., Tiraby M., Zhang Q., Cicuta P., Jouanguy E., Neyrolles O., RA Bryant C.E., Floto A.R., Goujon C., Lei F.Z., Martin-Blondel G., Silva S., RA Casanova J.L., Cougoule C., Reversade B., Marcoux J., Ravet E., Meunier E.; RT "Human NLRP1 is a sensor of pathogenic coronavirus 3CL proteases in lung RT epithelial cells."; RL Mol. Cell 82:2385-2400(2022). RN [37] RP FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF PRO-1278 AND LEU-1281. RX PubMed=33731929; DOI=10.1038/s41586-021-03320-w; RA Huang M., Zhang X., Toh G.A., Gong Q., Wang J., Han Z., Wu B., Zhong F., RA Chai J.; RT "Structural and biochemical mechanisms of NLRP1 inhibition by DPP9."; RL Nature 592:773-777(2021). RN [38] RP SUBCELLULAR LOCATION (MICROBIAL INFECTION), AND INTERACTION WITH HERPES RP VIRUS 8/HHV-8 PROTEINS ORF45. RX PubMed=35618833; DOI=10.1038/s41590-022-01199-x; RA Yang X., Zhou J., Liu C., Qu Y., Wang W., Xiao M.Z.X., Zhu F., Liu Z., RA Liang Q.; RT "KSHV-encoded ORF45 activates human NLRP1 inflammasome."; RL Nat. Immunol. 23:916-926(2022). RN [39] RP FUNCTION, PHOSPHORYLATION AT SER-93; SER-99; SER-101; SER-107; THR-112; RP SER-113; THR-114; THR-129; SER-132; SER-163; SER-168; SER-170; SER-173; RP THR-178; SER-179 AND THR-180, AND MUTAGENESIS OF 178-THR--THR-180. RX PubMed=35857590; DOI=10.1126/science.abl6324; RA Robinson K.S., Toh G.A., Rozario P., Chua R., Bauernfried S., Sun Z., RA Firdaus M.J., Bayat S., Nadkarni R., Poh Z.S., Tham K.C., Harapas C.R., RA Lim C.K., Chu W., Tay C.W.S., Tan K.Y., Zhao T., Bonnard C., Sobota R., RA Connolly J.E., Common J., Masters S.L., Chen K.W., Ho L., Wu B., RA Hornung V., Zhong F.L.; RT "ZAKalpha-driven ribotoxic stress response activates the human NLRP1 RT inflammasome."; RL Science 377:328-335(2022). RN [40] {ECO:0007744|PDB:1PN5} RP STRUCTURE BY NMR OF 1-93. RX PubMed=14527388; DOI=10.1016/j.str.2003.08.009; RA Hiller S., Kohl A., Fiorito F., Herrmann T., Wider G., Tschopp J., RA Gruetter M.G., Wuethrich K.; RT "NMR structure of the apoptosis- and inflammation-related NALP1 pyrin RT domain."; RL Structure 11:1199-1205(2003). RN [41] {ECO:0007744|PDB:3KAT} RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 1371-1467. RG Northeast structural genomics consortium (NESG); RT "Northeast structural genomics consortium target HR3486E."; RL Submitted (OCT-2009) to the PDB data bank. RN [42] {ECO:0007744|PDB:6X6C} RP STRUCTURE BY ELECTRON MICROSCOPY (2.90 ANGSTROMS) IN COMPLEX WITH DPP9, RP FUNCTION, ACTIVITY REGULATION, INTERACTION WITH DPP9, MUTAGENESIS OF RP 1193-LEU-LEU-1194; SER-1213; HIS-1276; LYS-1277 AND GLU-1322, AND RP CHARACTERIZATION OF VARIANT AIADK ARG-1214. RX PubMed=33731932; DOI=10.1038/s41586-021-03350-4; RA Hollingsworth L.R., Sharif H., Griswold A.R., Fontana P., Mintseris J., RA Dagbay K.B., Paulo J.A., Gygi S.P., Bachovchin D.A., Wu H.; RT "DPP9 sequesters the C terminus of NLRP1 to repress inflammasome RT activation."; RL Nature 592:778-783(2021). RN [43] {ECO:0007744|PDB:6K7V} RP STRUCTURE BY ELECTRON MICROSCOPY (3.70 ANGSTROMS) OF 1379-1466, SUBCELLULAR RP LOCATION, SUBUNIT, DOMAIN, AND MUTAGENESIS OF ARG-1240; 1260-ARG-LYS-1261; RP 1278-PRO-PRO-1279; PHE-1320; ASP-1383; ARG-1386; GLU-1387; GLN-1388; RP ARG-1392; SER-1395; GLU-1397; LYS-1402; HIS-1404; GLN-1406; GLN-1410; RP GLU-1411; TYR-1413; GLU-1414; ARG-1415; ASN-1420; ARG-1422; ARG-1427; RP LYS-1428; GLN-1434; ASP-1437; LYS-1449; GLU-1450; THR-1451; HIS-1454; RP GLU-1458 AND GLU-1461. RX PubMed=33420028; DOI=10.1038/s41467-020-20319-5; RA Gong Q., Robinson K., Xu C., Huynh P.T., Chong K.H.C., Tan E.Y.J., RA Zhang J., Boo Z.Z., Teo D.E.T., Lay K., Zhang Y., Lim J.S.Y., Goh W.I., RA Wright G., Zhong F.L., Reversade B., Wu B.; RT "Structural basis for distinct inflammasome complex assembly by human NLRP1 RT and CARD8."; RL Nat. Commun. 12:188-188(2021). RN [44] {ECO:0007744|PDB:6XKK} RP STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS) OF 1379-1473, SUBCELLULAR RP LOCATION, SUBUNIT, DOMAIN, AND MUTAGENESIS OF ARG-1392; GLU-1397; ASP-1401; RP GLU-1411; GLU-1414; ARG-1427; TYR-1445; MET-1457; TRP-1460 AND GLU-1461. RX PubMed=33420033; DOI=10.1038/s41467-020-20320-y; RA Robert Hollingsworth L., David L., Li Y., Griswold A.R., Ruan J., RA Sharif H., Fontana P., Orth-He E.L., Fu T.M., Bachovchin D.A., Wu H.; RT "Mechanism of filament formation in UPA-promoted CARD8 and NLRP1 RT inflammasomes."; RL Nat. Commun. 12:189-189(2021). RN [45] RP INVOLVEMENT IN VAMAS1, AND VARIANT HIS-155. RX PubMed=17377159; DOI=10.1056/nejmoa061592; RA Jin Y., Mailloux C.M., Gowan K., Riccardi S.L., LaBerge G., Bennett D.C., RA Fain P.R., Spritz R.A.; RT "NALP1 in vitiligo-associated multiple autoimmune disease."; RL N. Engl. J. Med. 356:1216-1225(2007). RN [46] RP VARIANT MSPC THR-77, AND TISSUE SPECIFICITY. RX PubMed=23349227; DOI=10.1136/jmedgenet-2012-101325; RA Soler V.J., Tran-Viet K.N., Galiacy S.D., Limviphuvadh V., Klemm T.P., RA St Germain E., Fournie P.R., Guillaud C., Maurer-Stroh S., Hawthorne F., RA Suarez C., Kantelip B., Afshari N.A., Creveaux I., Luo X., Meng W., RA Calvas P., Cassagne M., Arne J.L., Rozen S.G., Malecaze F., Young T.L.; RT "Whole exome sequencing identifies a mutation for a novel form of corneal RT intraepithelial dyskeratosis."; RL J. Med. Genet. 50:246-254(2013). RN [47] RP VARIANTS MSPC THR-54; VAL-66 AND 787-PHE--ARG-843 DEL, CHARACTERIZATION OF RP VARIANTS MSPC THR-54; VAL-66 AND 787-PHE--ARG-843 DEL, FUNCTION, AND TISSUE RP SPECIFICITY. RX PubMed=27662089; DOI=10.1016/j.cell.2016.09.001; RA Zhong F.L., Mamai O., Sborgi L., Boussofara L., Hopkins R., Robinson K., RA Szeverenyi I., Takeichi T., Balaji R., Lau A., Tye H., Roy K., Bonnard C., RA Ahl P.J., Jones L.A., Baker P., Lacina L., Otsuka A., Fournie P.R., RA Malecaze F., Lane E.B., Akiyama M., Kabashima K., Connolly J.E., RA Masters S.L., Soler V.J., Omar S.S., McGrath J.A., Nedelcu R., Gribaa M., RA Denguezli M., Saad A., Hiller S., Reversade B.; RT "Germline NLRP1 mutations cause skin inflammatory and cancer susceptibility RT syndromes via inflammasome activation."; RL Cell 167:187-202(2016). RN [48] RP INVOLVEMENT IN AIADK, AND VARIANTS AIADK TRP-726 AND ARG-1214. RX PubMed=27965258; DOI=10.1136/annrheumdis-2016-210021; RA Grandemange S., Sanchez E., Louis-Plence P., Tran Mau-Them F., Bessis D., RA Coubes C., Frouin E., Seyger M., Girard M., Puechberty J., Costes V., RA Rodiere M., Carbasse A., Jeziorski E., Portales P., Sarrabay G., RA Mondain M., Jorgensen C., Apparailly F., Hoppenreijs E., Touitou I., RA Genevieve D.; RT "A new autoinflammatory and autoimmune syndrome associated with NLRP1 RT mutations: NAIAD (NLRP1-associated autoinflammation with arthritis and RT dyskeratosis)."; RL Ann. Rheum. Dis. 76:1191-1198(2017). RN [49] RP INVOLVEMENT IN JRRP, FUNCTION, VARIANT JRRP ASN-755, AND CHARACTERIZATION RP OF VARIANT JRRP ASN-755. RX PubMed=31484767; DOI=10.1073/pnas.1906184116; RA Drutman S.B., Haerynck F., Zhong F.L., Hum D., Hernandez N.J., Belkaya S., RA Rapaport F., de Jong S.J., Creytens D., Tavernier S.J., Bonte K., RA De Schepper S., van der Werff Ten Bosch J., Lorenzo-Diaz L., Wullaert A., RA Bossuyt X., Orth G., Bonagura V.R., Beziat V., Abel L., Jouanguy E., RA Reversade B., Casanova J.L.; RT "Homozygous NLRP1 gain-of-function mutation in siblings with a syndromic RT form of recurrent respiratory papillomatosis."; RL Proc. Natl. Acad. Sci. U.S.A. 116:19055-19063(2019). RN [50] RP CHARACTERIZATION OF VARIANT MSPC THR-77, FUNCTION, ACTIVITY REGULATION, RP PROTEOLYTIC CLEAVAGE (MICROBIAL INFECTION), UBIQUITINATION, AND MUTAGENESIS RP OF GLN-76; GLN-85; GLN-87; GLN-110; GLN-130; GLN-139; GLN-158; GLN-171; RP GLN-191; GLN-199; GLN-205 AND PHE-1212. RX PubMed=33093214; DOI=10.1126/science.aay2002; RA Robinson K.S., Teo D.E.T., Tan K.S., Toh G.A., Ong H.H., Lim C.K., Lay K., RA Au B.V., Lew T.S., Chu J.J.H., Chow V.T.K., Wang Y., Zhong F.L., RA Reversade B.; RT "Enteroviral 3C protease activates the human NLRP1 inflammasome in airway RT epithelia."; RL Science 0:0-0(2020). CC -!- FUNCTION: Acts as the sensor component of the NLRP1 inflammasome, which CC mediates inflammasome activation in response to various pathogen- CC associated signals, leading to subsequent pyroptosis (PubMed:22665479, CC PubMed:12191486, PubMed:17349957, PubMed:27662089, PubMed:31484767, CC PubMed:33093214, PubMed:33410748, PubMed:33731929, PubMed:33731932, CC PubMed:35857590). Inflammasomes are supramolecular complexes that CC assemble in the cytosol in response to pathogens and other damage- CC associated signals and play critical roles in innate immunity and CC inflammation (PubMed:22665479, PubMed:12191486, PubMed:17349957). Acts CC as a recognition receptor (PRR): recognizes specific pathogens and CC other damage-associated signals, such as cleavage by some human CC enteroviruses and rhinoviruses, double-stranded RNA, UV-B irradiation, CC or Val-boroPro inhibitor, and mediates the formation of the CC inflammasome polymeric complex composed of NLRP1, CASP1 and PYCARD/ASC CC (PubMed:22665479, PubMed:12191486, PubMed:17349957, PubMed:25562666, CC PubMed:30291141, PubMed:30096351, PubMed:33243852, PubMed:33093214, CC PubMed:33410748, PubMed:35857590). In response to pathogen-associated CC signals, the N-terminal part of NLRP1 is degraded by the proteasome, CC releasing the cleaved C-terminal part of the protein (NACHT, LRR and CC PYD domains-containing protein 1, C-terminus), which polymerizes and CC associates with PYCARD/ASC to initiate the formation of the CC inflammasome complex: the NLRP1 inflammasome recruits pro-caspase-1 CC (proCASP1) and promotes caspase-1 (CASP1) activation, which CC subsequently cleaves and activates inflammatory cytokines IL1B and IL18 CC and gasdermin-D (GSDMD), leading to pyroptosis (PubMed:22665479, CC PubMed:12191486, PubMed:17349957, PubMed:32051255, PubMed:33093214). In CC the absence of GSDMD expression, the NLRP1 inflammasome is able to CC recruit and activate CASP8, leading to activation of gasdermin-E CC (GSDME) (PubMed:33852854, PubMed:35594856). Activation of NLRP1 CC inflammasome is also required for HMGB1 secretion; the active cytokines CC and HMGB1 stimulate inflammatory responses (PubMed:22801494). Binds ATP CC and shows ATPase activity (PubMed:11113115, PubMed:15212762, CC PubMed:33243852). Plays an important role in antiviral immunity and CC inflammation in the human airway epithelium (PubMed:33093214). CC Specifically recognizes a number of pathogen-associated signals: upon CC infection by human rhinoviruses 14 and 16 (HRV-14 and HRV-16), NLRP1 is CC cleaved and activated which triggers NLRP1-dependent inflammasome CC activation and IL18 secretion (PubMed:33093214). Positive-strand RNA CC viruses, such as Semliki forest virus and long dsRNA activate the NLRP1 CC inflammasome, triggering IL1B release in a NLRP1-dependent fashion CC (PubMed:33243852). Acts as a direct sensor for long dsRNA and thus RNA CC virus infection (PubMed:33243852). May also be activated by muramyl CC dipeptide (MDP), a fragment of bacterial peptidoglycan, in a NOD2- CC dependent manner (PubMed:18511561). The NLRP1 inflammasome is also CC activated in response to UV-B irradiation causing ribosome collisions: CC ribosome collisions cause phosphorylation and activation of NLRP1 in a CC MAP3K20-dependent manner, leading to pyroptosis (PubMed:35857590). CC {ECO:0000269|PubMed:11113115, ECO:0000269|PubMed:12191486, CC ECO:0000269|PubMed:15212762, ECO:0000269|PubMed:17349957, CC ECO:0000269|PubMed:18511561, ECO:0000269|PubMed:22665479, CC ECO:0000269|PubMed:22801494, ECO:0000269|PubMed:25562666, CC ECO:0000269|PubMed:27662089, ECO:0000269|PubMed:30096351, CC ECO:0000269|PubMed:30291141, ECO:0000269|PubMed:31484767, CC ECO:0000269|PubMed:32051255, ECO:0000269|PubMed:33093214, CC ECO:0000269|PubMed:33243852, ECO:0000269|PubMed:33410748, CC ECO:0000269|PubMed:33731929, ECO:0000269|PubMed:33731932, CC ECO:0000269|PubMed:33852854, ECO:0000269|PubMed:35594856, CC ECO:0000269|PubMed:35857590}. CC -!- FUNCTION: [NACHT, LRR and PYD domains-containing protein 1]: CC Constitutes the precursor of the NLRP1 inflammasome, which mediates CC autoproteolytic processing within the FIIND domain to generate the N- CC terminal and C-terminal parts, which are associated non-covalently in CC absence of pathogens and other damage-associated signals. CC {ECO:0000269|PubMed:22087307}. CC -!- FUNCTION: [NACHT, LRR and PYD domains-containing protein 1, N- CC terminus]: Regulatory part that prevents formation of the NLRP1 CC inflammasome: in absence of pathogens and other damage-associated CC signals, interacts with the C-terminal part of NLRP1 (NACHT, LRR and CC PYD domains-containing protein 1, C-terminus), preventing activation of CC the NLRP1 inflammasome (PubMed:33093214). In response to pathogen- CC associated signals, this part is ubiquitinated and degraded by the CC proteasome, releasing the cleaved C-terminal part of the protein, which CC polymerizes and forms the NLRP1 inflammasome (PubMed:33093214). CC {ECO:0000269|PubMed:33093214}. CC -!- FUNCTION: [NACHT, LRR and PYD domains-containing protein 1, C- CC terminus]: Constitutes the active part of the NLRP1 inflammasome CC (PubMed:33093214, PubMed:33731929, PubMed:33731932). In absence of CC pathogens and other damage-associated signals, interacts with the N- CC terminal part of NLRP1 (NACHT, LRR and PYD domains-containing protein CC 1, N-terminus), preventing activation of the NLRP1 inflammasome CC (PubMed:33093214). In response to pathogen-associated signals, the N- CC terminal part of NLRP1 is degraded by the proteasome, releasing this CC form, which polymerizes and associates with PYCARD/ASC to form of the CC NLRP1 inflammasome complex: the NLRP1 inflammasome complex then CC directly recruits pro-caspase-1 (proCASP1) and promotes caspase-1 CC (CASP1) activation, leading to gasdermin-D (GSDMD) cleavage and CC subsequent pyroptosis (PubMed:33093214). {ECO:0000269|PubMed:33093214, CC ECO:0000269|PubMed:33731929, ECO:0000269|PubMed:33731932}. CC -!- FUNCTION: [Isoform 2]: It is unclear whether is involved in CC inflammasome formation. It is not cleaved within the FIIND domain, does CC not assemble into specks, nor promote IL1B release (PubMed:22665479). CC However, in an vitro cell-free system, it has been shown to be CC activated by MDP (PubMed:17349957). {ECO:0000269|PubMed:17349957, CC ECO:0000269|PubMed:22665479}. 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:33243852}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066; CC Evidence={ECO:0000269|PubMed:33243852}; CC -!- ACTIVITY REGULATION: NLRP1 inflammasome is activated by cleavage by the CC Protease 3C from various human enteroviruses and rhinoviruses (EV68, CC EV71, Coxsackievirus B3, HRV-14 and HRV-16): cleavage promotes CC ubiquitination and degradation of the N-terminal part, releasing the CC cleaved C-terminal part of the protein (NACHT, LRR and PYD domains- CC containing protein 1, C-terminus), which polymerizes and forms the CC NLRP1 inflammasome (PubMed:33093214, PubMed:33410748). NLRP1 CC inflammasome is also activated by cleavage by the 3C-like proteinase CC nsp5 from human coronavirus SARS-CoV-2 (PubMed:35594856). Activated CC double-stranded RNA: positive-strand RNA viruses such as Semliki forest CC virus and long dsRNA activate the NLRP1 inflammasome (PubMed:33243852). CC In contrast to its mouse ortholog, not activated by Bacillus anthracis CC lethal toxin (PubMed:19651869). NLRP1 inflammasome is inhibited by DPP8 CC and DPP9, which sequester the C-terminal fragment of NLRP1 (NACHT, LRR CC and PYD domains-containing protein 1, C-terminus) in a ternary complex, CC thereby preventing NLRP1 oligomerization and activation CC (PubMed:30291141, PubMed:31525884, PubMed:33731929, PubMed:33731932). CC NLRP1 inflammasome is activated by Val-boroPro (Talabostat, PT-100), an CC inhibitor of dipeptidyl peptidases DPP8 and DPP9 (PubMed:30291141, CC PubMed:33731929, PubMed:33731932). Val-boroPro relieves inhibition of CC DPP8 and/or DPP9 by promoting disruption of the ternary complex, CC releasing its C-terminal part from autoinhibition (PubMed:33731929, CC PubMed:33731932). ATPase activity is activated by dsRNA-binding but not CC dsDNA-binding (PubMed:33243852). {ECO:0000269|PubMed:19651869, CC ECO:0000269|PubMed:30291141, ECO:0000269|PubMed:31525884, CC ECO:0000269|PubMed:33093214, ECO:0000269|PubMed:33243852, CC ECO:0000269|PubMed:33410748, ECO:0000269|PubMed:33731929, CC ECO:0000269|PubMed:33731932, ECO:0000269|PubMed:35594856}. CC -!- ACTIVITY REGULATION: (Microbial infection) The NLRP1 inflammasome is CC activated by human herpes virus 8/HHV-8 protein ORF45, which interacts CC with the N-terminal part of NLRP1 and promotes its translocation into CC the nucleus, relieving autoinhibition and leading to activation. CC {ECO:0000269|PubMed:35618833}. CC -!- SUBUNIT: Interacts (via LRR repeats) with BCL2 and BCL2L1 (via the loop CC between motifs BH4 and BH3); these interactions reduce NLRP1 CC inflammasome-induced CASP1 activation and IL1B release, possibly by CC impairing NLRP1 interaction with PYCARD (PubMed:17418785). Interacts CC with NOD2; this interaction is enhanced in the presence of muramyl CC dipeptide (MDP) and increases IL1B release (PubMed:18511561). Interacts CC with EIF2AK2/PKR; this interaction requires EIF2AK2 activity, is CC accompanied by EIF2AK2 autophosphorylation and promotes inflammasome CC assembly in response to danger-associated signals (PubMed:22801494). CC Interacts with MEFV; this interaction targets NLRP1 to degradation by CC autophagy, hence preventing excessive IL1B- and IL18-mediated CC inflammation (PubMed:17431422, PubMed:26347139). Binds (via LRR domain) CC to dsDNA and dsRNA (PubMed:33243852). Interacts with DPP9; leading to CC inhibit activation of the inflammasome (PubMed:30291141, CC PubMed:31525884, PubMed:33731932). DPP9 acts via formation of a ternary CC complex, composed of a DPP9 homodimer, one full-length NLRP1 protein, CC and one cleaved C-terminus of NLRP1 (NACHT, LRR and PYD domains- CC containing protein 1, C-terminus) (PubMed:33731932). Interacts with CC DPP8; leading to inhibit activation of the inflammasome, probably via CC formation of a ternary complex with DPP8 (PubMed:31525884). CC {ECO:0000269|PubMed:17418785, ECO:0000269|PubMed:17431422, CC ECO:0000269|PubMed:18511561, ECO:0000269|PubMed:22801494, CC ECO:0000269|PubMed:26347139, ECO:0000269|PubMed:30291141, CC ECO:0000269|PubMed:31525884, ECO:0000269|PubMed:33243852, CC ECO:0000269|PubMed:33731932}. CC -!- SUBUNIT: [NACHT, LRR and PYD domains-containing protein 1, N-terminus]: CC Interacts with the C-terminal part of NLRP1 (NACHT, LRR and PYD CC domains-containing protein 1, C-terminus) in absence of pathogens and CC other damage-associated signals. {ECO:0000269|PubMed:33093214}. CC -!- SUBUNIT: [NACHT, LRR and PYD domains-containing protein 1, C-terminus]: CC Interacts with the N-terminal part of NLRP1 (NACHT, LRR and PYD CC domains-containing protein 1, N-terminus) in absence of pathogens and CC other damage-associated signals (PubMed:33093214). Homomultimer; forms CC the NLRP1 inflammasome polymeric complex, a filament composed of CC homopolymers of this form in response to pathogens and other damage- CC associated signals (PubMed:33420028, PubMed:33420033). The NLRP1 CC inflammasome polymeric complex associates with PYCARD/ASC CC (PubMed:22665479, PubMed:12191486, PubMed:17418785, PubMed:17349957). CC Interacts (via CARD domain) with PYCARD/ASC (via CARD domain); leading CC to pro-caspase-1 (proCASP1) recruitment (PubMed:22665479, CC PubMed:12191486, PubMed:17418785). Pro-caspase-1 (proCASP1) filament CC formation increases local enzyme concentration, resulting in trans- CC autocleavage and activation (PubMed:22665479, PubMed:12191486, CC PubMed:17349957). Active CASP1 then processes IL1B and IL18 precursors, CC leading to the release of mature cytokines in the extracellular milieu CC and inflammatory response (PubMed:22665479, PubMed:12191486, CC PubMed:17349957). {ECO:0000269|PubMed:12191486, CC ECO:0000269|PubMed:17349957, ECO:0000269|PubMed:17418785, CC ECO:0000269|PubMed:22665479, ECO:0000269|PubMed:33093214, CC ECO:0000269|PubMed:33420028, ECO:0000269|PubMed:33420033}. CC -!- SUBUNIT: (Microbial infection) Interacts with vaccinia virus protein F1 CC (PubMed:16439990). {ECO:0000269|PubMed:16439990}. CC -!- SUBUNIT: [NACHT, LRR and PYD domains-containing protein 1, N-terminus]: CC (Microbial infection) Interacts with human herpes virus 8/HHV-8 CC proteins ORF45; relieving autoinhibition of the NLRP1 inflammasome. CC {ECO:0000269|PubMed:35618833}. CC -!- INTERACTION: CC Q9C000; P10415: BCL2; NbExp=13; IntAct=EBI-1220518, EBI-77694; CC Q9C000; Q07817: BCL2L1; NbExp=9; IntAct=EBI-1220518, EBI-78035; CC Q9C000; Q07817-1: BCL2L1; NbExp=2; IntAct=EBI-1220518, EBI-287195; CC Q9C000; P29466: CASP1; NbExp=3; IntAct=EBI-1220518, EBI-516667; CC Q9C000; Q9ULZ3: PYCARD; NbExp=5; IntAct=EBI-1220518, EBI-751215; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:17418785}. CC Cytoplasm {ECO:0000269|PubMed:17164409}. Nucleus CC {ECO:0000269|PubMed:17164409}. Note=Nucleocytoplasmic distribution in CC lymphoid organs (probably in T-cells) and in neurons. In epithelial CC cells, predominantly cytoplasmic. {ECO:0000269|PubMed:17164409}. CC -!- SUBCELLULAR LOCATION: [NACHT, LRR and PYD domains-containing protein 1, CC C-terminus]: Inflammasome {ECO:0000269|PubMed:12191486, CC ECO:0000269|PubMed:22665479, ECO:0000269|PubMed:30291141, CC ECO:0000269|PubMed:33420028, ECO:0000269|PubMed:33420033}. CC -!- SUBCELLULAR LOCATION: [NACHT, LRR and PYD domains-containing protein 1, CC N-terminus]: Nucleus {ECO:0000269|PubMed:35618833}. Note=(Microbial CC infection) Interaction with human herpes virus 8/HHV-8 proteins ORF45 CC promotes translocation of the N-terminal part of NLRP1 into the CC nucleus, relieving autoinhibition of the NLRP1 inflammasome and leading CC to its activation. {ECO:0000269|PubMed:35618833}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; Synonyms=NAC beta {ECO:0000303|PubMed:11113115}, DEFCAP-L CC {ECO:0000303|PubMed:11076957}, NALP1-L {ECO:0000303|PubMed:15285719}; CC IsoId=Q9C000-1; Sequence=Displayed; CC Name=2; Synonyms=NAC alpha {ECO:0000303|PubMed:11113115}, DEFCAP-S CC {ECO:0000303|PubMed:11076957}, NALP1-S {ECO:0000303|PubMed:15285719}, CC NLRP1deltaEx14; CC IsoId=Q9C000-2; Sequence=VSP_004327; CC Name=3; Synonyms=NAC gamma {ECO:0000303|PubMed:11113115}; CC IsoId=Q9C000-3; Sequence=VSP_004326, VSP_004327; CC Name=4; Synonyms=NAC delta {ECO:0000303|PubMed:11113115}; CC IsoId=Q9C000-4; Sequence=VSP_004326; CC Name=5; CC IsoId=Q9C000-5; Sequence=VSP_053803, VSP_053804, VSP_053805; CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:11113115, CC PubMed:17164409). Abundantly expressed in primary immune cells (isoform CC 1 and isoform 2), including in neutrophils, monocytes/macrophages, CC dendritic cells (mostly Langerhans cells), and B- and T-lymphocytes (at CC protein level) (PubMed:15285719, PubMed:17164409). Strongly expressed CC in epithelial cells lining the glandular epithelium, such as that of CC the gastrointestinal tract (stomach, small intestine, colon), the CC respiratory tract (trachea and bronchi), and the endometrial and CC endocervical glands, gallbladder, prostate, and breast (at protein CC level). In testis, expressed in spermatogonia and primary CC spermatocytes, but not in Sertoli cells (at protein level). In the CC brain, expressed in neurons, in particular in pyramidal ones and in CC oligodendrocytes, but not detected in microglia (at protein level) CC (PubMed:17164409). Expressed in adult and fetal ocular tissues, CC including in adult and 24-week old fetal choroid, sclera, cornea, and CC optic nerve, as well as in adult retina and fetal retina/retinal CC pigment epithelium (PubMed:23349227). Highly expressed in the skin CC throughout the epidermis and in dermal fibroblasts, in both glabrous CC skin and plantar skin. It is detected in keratinocytes, but not in CC melanocytes. Expressed in epidermal appendages such as hair follicles CC (PubMed:27662089). {ECO:0000269|PubMed:11113115, CC ECO:0000269|PubMed:15285719, ECO:0000269|PubMed:17164409, CC ECO:0000269|PubMed:23349227, ECO:0000269|PubMed:27662089}. CC -!- DEVELOPMENTAL STAGE: Associated with differentiation in stratified CC epithelia of the skin, esophagus, intestine, and cervix, as well as in CC the prostate gland. Undetectable in undifferentiated basal cells, but CC expressed in differentiated luminal secretory cells (PubMed:11113115). CC Expressed in differentiated macrophages and granulocytes, but not their CC precursors (at protein level) (PubMed:11113115, PubMed:15285719). In CC testis, also associated with cell differentiation, with conflicting CC results. Expressed in spermatogonia and primary spermatocytes, but not CC in cells from later differentiation stages, including secondary CC spermatocytes, spermatids, and spermatozoa (at protein level) CC (PubMed:17164409). Not detected in spermatocytes, nor spermatids, and CC strongly expressed in spermatozoa (at protein level) (PubMed:11113115). CC {ECO:0000269|PubMed:11113115, ECO:0000269|PubMed:15285719, CC ECO:0000269|PubMed:17164409}. CC -!- INDUCTION: Up-regulated by ATF4 during endoplasmic reticulum (ER) CC stress response (PubMed:26086088). Up-regulated in arterial endothelial CC cells exposed to plasma from patients with peripheral arterial disease, CC but not to plasma from healthy controls (PubMed:24439873). CC {ECO:0000269|PubMed:24439873, ECO:0000269|PubMed:26086088}. CC -!- DOMAIN: The CARD domain, rather than the pyrin domain, is involved in CC the interaction with PYCARD, CASP1 and CASP5. CC {ECO:0000269|PubMed:12191486, ECO:0000269|PubMed:17349957, CC ECO:0000269|PubMed:22665479}. CC -!- DOMAIN: The ZAKalpha motifs are recognized and phosphorylated by CC isoform ZAKalpha of MAP3K20. {ECO:0000269|PubMed:35857590}. CC -!- DOMAIN: The leucine-rich repeat (LRR) domain may be involved in CC autoinhibition in the absence of activating signal, possibly through CC intramolecular interaction with the NACHT domain. Serves as the CC predominant binding domain for dsRNA and dsDNA (PubMed:33243852). CC {ECO:0000250|UniProtKB:Q9EPB4, ECO:0000269|PubMed:12191486, CC ECO:0000269|PubMed:17349957, ECO:0000269|PubMed:33243852}. CC -!- DOMAIN: The FIIND (domain with function to find) region is involved in CC homomerization, but not in CASP1-binding (By similarity). Autocatalytic CC cleavage in this region occurs constitutively, prior to activation CC signals, and is required for inflammasome activity (IL1B release), CC possibly by facilitating CASP1 binding (PubMed:22665479, CC PubMed:22087307). Both N- and C-terminal fragments remain associated CC (PubMed:22665479, PubMed:22087307). {ECO:0000250|UniProtKB:Q2LKW6, CC ECO:0000269|PubMed:22087307, ECO:0000269|PubMed:22665479}. CC -!- DOMAIN: The pyrin domain mediates an autoinhibitory function, CC potentially acting as a threshold modulator, which allows NLRP1 to CC discriminate long from short dsRNA. Inhibits ATPase activity of the CC NATCH domain. {ECO:0000269|PubMed:33243852}. CC -!- DOMAIN: [NACHT, LRR and PYD domains-containing protein 1, C-terminus]: CC The C-terminal part of NLRP1 oligomerizes to form the core of the NLRP1 CC inflammasome filament: in the filament, the CARD domains form a central CC helical filaments that are promoted by oligomerized, but flexibly CC linked, UPA regions surrounding the filaments (PubMed:33420028, CC PubMed:33420033). The UPA region reduces the threshold needed for CC filament formation and signaling (PubMed:33420028, PubMed:33420033). CC Must recruit the adapter PYCARD/ASC to facilitate CASP1 interaction and CC polymerization (PubMed:33420033). {ECO:0000269|PubMed:33420028, CC ECO:0000269|PubMed:33420033}. CC -!- DOMAIN: Upon dsRNA-binding via its LRR domain, NACHT domain gains CC ATPase activity which is inhibited by the pyrin domain. CC {ECO:0000269|PubMed:33243852}. CC -!- PTM: [NACHT, LRR and PYD domains-containing protein 1]: CC Autocatalytically cleaved (PubMed:22087307, PubMed:22665479, CC PubMed:33093214). Autocatalytic cleavage in FIIND region occurs CC constitutively, prior to activation signals, and is required for CC inflammasome activity (IL1B release), possibly by facilitating CASP1 CC binding (PubMed:22087307, PubMed:22665479, PubMed:33093214). Both CC N- and C-terminal parts remain associated non-covalently CC (PubMed:22087307, PubMed:22665479, PubMed:33093214). CC {ECO:0000269|PubMed:22087307, ECO:0000269|PubMed:22665479, CC ECO:0000269|PubMed:33093214}. CC -!- PTM: [NACHT, LRR and PYD domains-containing protein 1, N-terminus]: CC Ubiquitinated by the cullin:ZER1/ZYG11B complex in response to CC pathogen-associated signals, leading to its degradation by the CC proteasome and subsequent release of the cleaved C-terminal part of the CC protein (NACHT, LRR and PYD domains-containing protein 1, C-terminus), CC which polymerizes and forms the NLRP1 inflammasome. CC {ECO:0000269|PubMed:33093214}. CC -!- PTM: Phosphorylated by MAP3K20 isoform ZAKalpha, MAPK11 and MAPK14 in CC response to UV-B irradiation and ribosome collisions, promoting CC activation of the NLRP1 inflammasome and pyroptosis. CC {ECO:0000269|PubMed:35857590}. CC -!- PTM: (Microbial infection) Cleaved between Gln-130 and Gly-131 by the CC Protease 3C from various human enteroviruses and rhinoviruses (EV68, CC EV71, Coxsackievirus B3, HRV-14 and HRV-16) (PubMed:33093214, CC PubMed:33410748). This cleavage triggers N-glycine-mediated proteasomal CC degradation of the autoinhibitory NLRP1 N-terminal fragment via the CC cullin:ZER1/ZYG11B complex which liberates the activating C-terminal CC fragment and activates NLRP1 inflammasome (PubMed:33093214). CC {ECO:0000269|PubMed:33093214, ECO:0000269|PubMed:33410748}. CC -!- PTM: (Microbial infection) Cleaved between Gln-333 and Gly-334 by the CC 3C-like proteinase nsp5 from human coronavirus SARS-CoV-2 CC (PubMed:35594856). This cleavage liberates the activating C-terminal CC fragment and activates NLRP1 inflammasome, leading to downstream CC activation of GSDME and lung epithelial cell death (PubMed:35594856). CC {ECO:0000269|PubMed:35594856}. CC -!- DISEASE: Vitiligo-associated multiple autoimmune disease 1 (VAMAS1) CC [MIM:606579]: A disorder characterized by the association of vitiligo CC with several autoimmune and autoinflammatory diseases including CC autoimmune thyroid disease, rheumatoid arthritis and systemic lupus CC erythematosus. {ECO:0000269|PubMed:17377159}. Note=Disease CC susceptibility is associated with variants affecting the gene CC represented in this entry. CC -!- DISEASE: Palmoplantar carcinoma, multiple self-healing (MSPC) CC [MIM:615225]: An autosomal dominant disease characterized by CC keratopathy with neovascularization, bilateral corneal opacification, CC palmoplantar hyperkeratosis, dyshidrosis, dystrophic nails, and CC recurrent keratoacanthomas in palmoplantar skin as well as in CC conjunctival and corneal epithelia. In addition, patients experience a CC high susceptibility to malignant squamous cell carcinoma. CC {ECO:0000269|PubMed:23349227, ECO:0000269|PubMed:27662089, CC ECO:0000269|PubMed:33093214}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Autoinflammation with arthritis and dyskeratosis (AIADK) CC [MIM:617388]: A disorder characterized by recurrent fever, diffuse skin CC dyskeratosis, autoinflammation, autoimmunity, arthritis and high CC transitional B-cell level. Inheritance can be autosomal dominant or CC autosomal recessive. {ECO:0000269|PubMed:27965258, CC ECO:0000269|PubMed:30291141, ECO:0000269|PubMed:33731932}. Note=The CC disease may be caused by variants affecting the gene represented in CC this entry. CC -!- DISEASE: Respiratory papillomatosis, juvenile recurrent, congenital CC (JRRP) [MIM:618803]: An autosomal recessive disease characterized by CC recurrent growth of papillomas in the respiratory tract, and onset in CC early childhood. Papillomas are most commonly found in the larynx but CC may occur anywhere from the mouth to the bronchi. Children typically CC present within the first years of life with hoarseness or, in more CC severe cases, respiratory distress or stridor and airway obstruction. CC JRRP is associated with infection of the upper airway by human CC papillomaviruses of the alpha genus. The infection is thought to occur CC by vertical transmission at birth. {ECO:0000269|PubMed:31484767}. CC Note=The disease may be caused by variants affecting the gene CC represented in this entry. CC -!- MISCELLANEOUS: In macrophages and dendritic cells, NLRP1 inflammasome CC activation of CASP1 and IL1B maturation can be dampened by direct CC contact with activated effector and memory T-cells. This effect may be CC mediated by hexameric TNF ligands, such as CD40LG. CC {ECO:0000250|UniProtKB:Q2LKW6}. CC -!- SIMILARITY: Belongs to the NLRP family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA76770.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAB15469.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305}; CC Sequence=BAB15470.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF298548; AAG15254.1; -; mRNA. DR EMBL; AF310105; AAG30288.1; -; mRNA. DR EMBL; AF229059; AAK00748.1; -; mRNA. DR EMBL; AF229060; AAK00749.1; -; mRNA. DR EMBL; AF229061; AAK00750.1; -; mRNA. DR EMBL; AF229062; AAK00751.1; -; mRNA. DR EMBL; AB023143; BAA76770.2; ALT_INIT; mRNA. DR EMBL; AK026393; BAB15469.1; ALT_SEQ; mRNA. DR EMBL; AK026398; BAB15470.1; ALT_SEQ; mRNA. DR EMBL; AC055839; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC051787; AAH51787.1; -; mRNA. DR EMBL; AL117470; CAB55945.1; -; mRNA. DR CCDS; CCDS32537.1; -. [Q9C000-5] DR CCDS; CCDS42244.1; -. [Q9C000-4] DR CCDS; CCDS42245.1; -. [Q9C000-2] DR CCDS; CCDS42246.1; -. [Q9C000-1] DR CCDS; CCDS58508.1; -. [Q9C000-3] DR PIR; T17255; T17255. DR RefSeq; NP_001028225.1; NM_001033053.2. [Q9C000-5] DR RefSeq; NP_055737.1; NM_014922.4. [Q9C000-2] DR RefSeq; NP_127497.1; NM_033004.3. [Q9C000-1] DR RefSeq; NP_127499.1; NM_033006.3. [Q9C000-4] DR RefSeq; NP_127500.1; NM_033007.3. [Q9C000-3] DR PDB; 1PN5; NMR; -; A=1-93. DR PDB; 3KAT; X-ray; 3.10 A; A=1371-1467. DR PDB; 4IFP; X-ray; 1.99 A; A/B/C=1379-1462. DR PDB; 4IM6; X-ray; 1.65 A; A=791-990. DR PDB; 5Y3S; X-ray; 2.45 A; A/B/C/D=790-990. DR PDB; 6K7V; EM; 3.70 A; A/B/C/D/E/F/G/H/I/J/K/L=1379-1466. DR PDB; 6X6C; EM; 2.90 A; E/F=1-1473. DR PDB; 6XKK; EM; 3.60 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/a/b/c/d/e/f/g/h=1379-1473. DR PDB; 7WGE; EM; 3.40 A; A=95-994. DR PDBsum; 1PN5; -. DR PDBsum; 3KAT; -. DR PDBsum; 4IFP; -. DR PDBsum; 4IM6; -. DR PDBsum; 5Y3S; -. DR PDBsum; 6K7V; -. DR PDBsum; 6X6C; -. DR PDBsum; 6XKK; -. DR PDBsum; 7WGE; -. DR AlphaFoldDB; Q9C000; -. DR BMRB; Q9C000; -. DR EMDB; EMD-22074; -. DR EMDB; EMD-22075; -. DR EMDB; EMD-22220; -. DR EMDB; EMD-32484; -. DR EMDB; EMD-9943; -. DR SMR; Q9C000; -. DR BioGRID; 116529; 22. DR ComplexPortal; CPX-4082; NLRP1 inflammasome. DR CORUM; Q9C000; -. DR DIP; DIP-38407N; -. DR IntAct; Q9C000; 17. DR MINT; Q9C000; -. DR STRING; 9606.ENSP00000460475; -. DR BindingDB; Q9C000; -. DR ChEMBL; CHEMBL1741214; -. DR MEROPS; S79.002; -. DR iPTMnet; Q9C000; -. DR PhosphoSitePlus; Q9C000; -. DR BioMuta; NLRP1; -. DR DMDM; 17380146; -. DR EPD; Q9C000; -. DR MassIVE; Q9C000; -. DR PaxDb; 9606-ENSP00000478516; -. DR PeptideAtlas; Q9C000; -. DR ProteomicsDB; 19812; -. DR ProteomicsDB; 79931; -. [Q9C000-1] DR ProteomicsDB; 79932; -. [Q9C000-2] DR ProteomicsDB; 79933; -. [Q9C000-3] DR ProteomicsDB; 79934; -. [Q9C000-4] DR Antibodypedia; 3365; 286 antibodies from 36 providers. DR DNASU; 22861; -. DR Ensembl; ENST00000262467.11; ENSP00000262467.5; ENSG00000091592.17. [Q9C000-5] DR Ensembl; ENST00000269280.9; ENSP00000269280.4; ENSG00000091592.17. [Q9C000-2] DR Ensembl; ENST00000354411.8; ENSP00000346390.3; ENSG00000091592.17. [Q9C000-4] DR Ensembl; ENST00000544378.7; ENSP00000442029.2; ENSG00000091592.17. [Q9C000-5] DR Ensembl; ENST00000571451.7; ENSP00000459661.3; ENSG00000091592.17. [Q9C000-2] DR Ensembl; ENST00000572272.6; ENSP00000460475.1; ENSG00000091592.17. [Q9C000-1] DR Ensembl; ENST00000576905.6; ENSP00000458303.2; ENSG00000091592.17. [Q9C000-2] DR Ensembl; ENST00000577119.5; ENSP00000460216.1; ENSG00000091592.17. [Q9C000-3] DR Ensembl; ENST00000617618.5; ENSP00000478516.1; ENSG00000091592.17. [Q9C000-1] DR Ensembl; ENST00000699709.1; ENSP00000514534.1; ENSG00000091592.17. [Q9C000-1] DR GeneID; 22861; -. DR KEGG; hsa:22861; -. DR MANE-Select; ENST00000572272.6; ENSP00000460475.1; NM_033004.4; NP_127497.1. DR UCSC; uc002gcg.2; human. [Q9C000-1] DR AGR; HGNC:14374; -. DR DisGeNET; 22861; -. DR GeneCards; NLRP1; -. DR HGNC; HGNC:14374; NLRP1. DR HPA; ENSG00000091592; Low tissue specificity. DR MalaCards; NLRP1; -. DR MIM; 606579; phenotype. DR MIM; 606636; gene. DR MIM; 615225; phenotype. DR MIM; 617388; phenotype. DR MIM; 618803; phenotype. DR neXtProt; NX_Q9C000; -. DR OpenTargets; ENSG00000091592; -. DR Orphanet; 352662; Corneal intraepithelial dyskeratosis-palmoplantar hyperkeratosis-laryngeal dyskeratosis syndrome. DR Orphanet; 3435; NON RARE IN EUROPE: Vitiligo. DR PharmGKB; PA162397797; -. DR VEuPathDB; HostDB:ENSG00000091592; -. DR eggNOG; ENOG502S4A4; Eukaryota. DR GeneTree; ENSGT00940000162176; -. DR HOGENOM; CLU_002274_2_4_1; -. DR InParanoid; Q9C000; -. DR OMA; SWMVCTC; -. DR OrthoDB; 338452at2759; -. DR PhylomeDB; Q9C000; -. DR TreeFam; TF340267; -. DR PathwayCommons; Q9C000; -. DR Reactome; R-HSA-844455; The NLRP1 inflammasome. DR SignaLink; Q9C000; -. DR SIGNOR; Q9C000; -. DR BioGRID-ORCS; 22861; 13 hits in 1160 CRISPR screens. DR ChiTaRS; NLRP1; human. DR EvolutionaryTrace; Q9C000; -. DR GeneWiki; NLRP1; -. DR GenomeRNAi; 22861; -. DR Pharos; Q9C000; Tbio. DR PRO; PR:Q9C000; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q9C000; Protein. DR Bgee; ENSG00000091592; Expressed in granulocyte and 125 other cell types or tissues. DR ExpressionAtlas; Q9C000; baseline and differential. DR GO; GO:0061702; C:canonical inflammasome complex; IBA:GO_Central. DR GO; GO:0005737; C:cytoplasm; NAS:ComplexPortal. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0072558; C:NLRP1 inflammasome complex; IDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; NAS:ComplexPortal. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL. 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:UniProtKB. DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; NAS:UniProtKB. DR GO; GO:0003690; F:double-stranded DNA binding; IDA:UniProtKB. DR GO; GO:0003725; F:double-stranded RNA binding; IDA:UniProtKB. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0140693; F:molecular condensate scaffold activity; IDA:UniProt. DR GO; GO:0038187; F:pattern recognition receptor activity; IDA:UniProt. DR GO; GO:0008233; F:peptidase activity; IEA:UniProtKB-KW. DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB. DR GO; GO:0043621; F:protein self-association; IDA:UniProtKB. DR GO; GO:0035591; F:signaling adaptor activity; IDA:UniProt. DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:HGNC-UCL. DR GO; GO:0140374; P:antiviral innate immune response; IDA:UniProtKB. DR GO; GO:0006915; P:apoptotic process; NAS:UniProtKB. DR GO; GO:0071493; P:cellular response to UV-B; IMP:UniProtKB. DR GO; GO:0042742; P:defense response to bacterium; ISS:BHF-UCL. DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB. DR GO; GO:0051402; P:neuron apoptotic process; IDA:HGNC-UCL. DR GO; GO:1904784; P:NLRP1 inflammasome complex assembly; IDA:UniProt. DR GO; GO:0002221; P:pattern recognition receptor signaling pathway; NAS:ComplexPortal. DR GO; GO:0050729; P:positive regulation of inflammatory response; IDA:ComplexPortal. DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IDA:UniProtKB. DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB. DR GO; GO:0070269; P:pyroptosis; IDA:UniProtKB. DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro. DR GO; GO:0050727; P:regulation of inflammatory response; IC:BHF-UCL. DR GO; GO:0032495; P:response to muramyl dipeptide; ISS:BHF-UCL. DR GO; GO:0097264; P:self proteolysis; IDA:UniProtKB. DR GO; GO:0031098; P:stress-activated protein kinase signaling cascade; IMP:UniProtKB. DR CDD; cd08330; CARD_ASC_NALP1; 1. DR CDD; cd08320; Pyrin_NALPs; 1. DR DisProt; DP00554; -. DR Gene3D; 1.10.533.10; Death Domain, Fas; 2. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 1. DR InterPro; IPR001315; CARD. DR InterPro; IPR033516; CARD8/ASC/NALP1_CARD. DR InterPro; IPR004020; DAPIN. DR InterPro; IPR011029; DEATH-like_dom_sf. DR InterPro; IPR025307; FIIND_dom. DR InterPro; IPR001611; Leu-rich_rpt. DR InterPro; IPR032675; LRR_dom_sf. DR InterPro; IPR007111; NACHT_NTPase. DR InterPro; IPR041267; NLRP_HD2. DR InterPro; IPR041075; NOD2_WH. DR InterPro; IPR027417; P-loop_NTPase. DR PANTHER; PTHR46985; NACHT, LRR AND PYD DOMAINS-CONTAINING PROTEIN 1; 1. DR PANTHER; PTHR46985:SF3; NACHT, LRR AND PYD DOMAINS-CONTAINING PROTEIN 1; 1. DR Pfam; PF00619; CARD; 1. DR Pfam; PF13553; FIIND; 1. DR Pfam; PF00560; LRR_1; 1. DR Pfam; PF13516; LRR_6; 2. DR Pfam; PF05729; NACHT; 1. DR Pfam; PF17776; NLRC4_HD2; 1. DR Pfam; PF17779; NOD2_WH; 1. DR Pfam; PF02758; PYRIN; 1. DR PRINTS; PR00364; DISEASERSIST. DR SMART; SM00368; LRR_RI; 5. DR SMART; SM01289; PYRIN; 1. DR SUPFAM; SSF47986; DEATH domain; 2. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR SUPFAM; SSF52047; RNI-like; 1. DR PROSITE; PS50209; CARD; 1. DR PROSITE; PS50824; DAPIN; 1. DR PROSITE; PS51830; FIIND; 1. DR PROSITE; PS51450; LRR; 3. DR PROSITE; PS50837; NACHT; 1. DR Genevisible; Q9C000; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Cytoplasm; KW Direct protein sequencing; Disease variant; Ectodermal dysplasia; KW Host-virus interaction; Hydrolase; Immunity; Inflammasome; KW Inflammatory response; Innate immunity; Leucine-rich repeat; Necrosis; KW Nucleotide-binding; Nucleus; Phosphoprotein; Protease; Reference proteome; KW Repeat; Ubl conjugation. FT CHAIN 1..1473 FT /note="NACHT, LRR and PYD domains-containing protein 1" FT /id="PRO_0000096710" FT CHAIN 1..1212 FT /note="NACHT, LRR and PYD domains-containing protein 1, N- FT terminus" FT /evidence="ECO:0000305|PubMed:22665479" FT /id="PRO_0000452851" FT CHAIN 1213..1473 FT /note="NACHT, LRR and PYD domains-containing protein 1, C- FT terminus" FT /evidence="ECO:0000305|PubMed:22665479" FT /id="PRO_0000452852" FT DOMAIN 1..92 FT /note="Pyrin" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00061" FT DOMAIN 328..637 FT /note="NACHT" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136" FT REPEAT 809..830 FT /note="LRR 1" FT REPEAT 838..858 FT /note="LRR 2" FT REPEAT 866..887 FT /note="LRR 3" FT REPEAT 895..915 FT /note="LRR 4" FT REPEAT 923..944 FT /note="LRR 5" FT REPEAT 950..973 FT /note="LRR 6" FT DOMAIN 1079..1364 FT /note="FIIND" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01174" FT DOMAIN 1374..1463 FT /note="CARD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046" FT REGION 90..113 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 160..254 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 991..1017 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1079..1212 FT /note="ZU5" FT /evidence="ECO:0000303|PubMed:22087307" FT REGION 1213..1364 FT /note="UPA" FT /evidence="ECO:0000303|PubMed:22087307" FT MOTIF 111..117 FT /note="ZAKalpha motif 1" FT /evidence="ECO:0000269|PubMed:35857590" FT MOTIF 177..183 FT /note="ZAKalpha motif 2" FT /evidence="ECO:0000269|PubMed:35857590" FT COMPBIAS 160..187 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 215..231 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 997..1015 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 334..341 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136" FT SITE 130..131 FT /note="(Microbial infection) Cleavage; by human rhinovirus FT 14 (HRV-14) Protease 3C" FT /evidence="ECO:0000269|PubMed:33093214, FT ECO:0000269|PubMed:33410748" FT SITE 333..334 FT /note="(Microbial infection) Cleavage; by coronavirus SARS- FT CoV-2 proteinase nsp5" FT /evidence="ECO:0000269|PubMed:35594856" FT SITE 1212..1213 FT /note="Cleavage; by autolysis" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01174, FT ECO:0000269|PubMed:22665479" FT MOD_RES 93 FT /note="Phosphoserine; by MAPK11 and MAPK14" FT /evidence="ECO:0000269|PubMed:35857590" FT MOD_RES 99 FT /note="Phosphoserine; by MAPK11 and MAPK14" FT /evidence="ECO:0000269|PubMed:35857590" FT MOD_RES 101 FT /note="Phosphoserine; by MAPK11 and MAPK14" FT /evidence="ECO:0000269|PubMed:35857590" FT MOD_RES 107 FT /note="Phosphoserine; by MAPK14" FT /evidence="ECO:0000269|PubMed:35857590" FT MOD_RES 112 FT /note="Phosphothreonine; by MAPK11, MAPK14 and MAP3K20" FT /evidence="ECO:0000269|PubMed:35857590" FT MOD_RES 113 FT /note="Phosphoserine; by MAP3K20" FT /evidence="ECO:0000269|PubMed:35857590" FT MOD_RES 114 FT /note="Phosphothreonine; by MAP3K20" FT /evidence="ECO:0000269|PubMed:35857590" FT MOD_RES 129 FT /note="Phosphothreonine; by MAP3K20" FT /evidence="ECO:0000269|PubMed:35857590" FT MOD_RES 132 FT /note="Phosphoserine; by MAP3K20" FT /evidence="ECO:0000269|PubMed:35857590" FT MOD_RES 163 FT /note="Phosphoserine; by MAPK14" FT /evidence="ECO:0000269|PubMed:35857590" FT MOD_RES 168 FT /note="Phosphoserine; by MAPK11 and MAPk14" FT /evidence="ECO:0000269|PubMed:35857590" FT MOD_RES 170 FT /note="Phosphoserine; by MAPK11 and MAPK14" FT /evidence="ECO:0000269|PubMed:35857590" FT MOD_RES 173 FT /note="Phosphoserine; by MAPK11" FT /evidence="ECO:0000269|PubMed:35857590" FT MOD_RES 178 FT /note="Phosphothreonine; by MAPK11" FT /evidence="ECO:0000269|PubMed:35857590" FT MOD_RES 179 FT /note="Phosphoserine; by MAPK11 and MAP3K20" FT /evidence="ECO:0000269|PubMed:35857590" FT MOD_RES 180 FT /note="Phosphothreonine; by MAPK11 and MAP3K20" FT /evidence="ECO:0000269|PubMed:35857590" FT VAR_SEQ 958..987 FT /note="Missing (in isoform 3 and isoform 4)" FT /evidence="ECO:0000303|PubMed:11113115" FT /id="VSP_004326" FT VAR_SEQ 1044 FT /note="A -> AGKSH (in isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_053803" FT VAR_SEQ 1262..1305 FT /note="Missing (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:10231032, FT ECO:0000303|PubMed:11076957, ECO:0000303|PubMed:11113115, FT ECO:0000303|PubMed:11250163, ECO:0000303|PubMed:11270363" FT /id="VSP_004327" FT VAR_SEQ 1354..1371 FT /note="DLMPATTLIPPARIAVPS -> RNTSQPWNLRCNRDARRY (in isoform FT 5)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_053804" FT VAR_SEQ 1372..1473 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_053805" FT VARIANT 54 FT /note="A -> T (in MSPC; increased NLRP1-inflammasome FT complex assembly; altered protein folding; FT dbSNP:rs1057519492)" FT /evidence="ECO:0000269|PubMed:27662089" FT /id="VAR_078798" FT VARIANT 66 FT /note="A -> V (in MSPC; increased NLRP1-inflammasome FT complex assembly; altered protein folding; FT dbSNP:rs1057519493)" FT /evidence="ECO:0000269|PubMed:27662089" FT /id="VAR_078799" FT VARIANT 77 FT /note="M -> T (in MSPC; destabilization of the N-terminal FT fragment; dbSNP:rs397514692)" FT /evidence="ECO:0000269|PubMed:23349227, FT ECO:0000269|PubMed:33093214" FT /id="VAR_069901" FT VARIANT 155 FT /note="L -> H (risk factor for VAMAS1; dbSNP:rs12150220)" FT /evidence="ECO:0000269|PubMed:11270363, FT ECO:0000269|PubMed:17377159" FT /id="VAR_033239" FT VARIANT 246 FT /note="T -> S (in dbSNP:rs11651595)" FT /evidence="ECO:0000269|PubMed:11270363" FT /id="VAR_024238" FT VARIANT 404 FT /note="R -> Q (in dbSNP:rs3744718)" FT /id="VAR_021886" FT VARIANT 726 FT /note="R -> W (in AIADK; uncertain significance; FT dbSNP:rs776245016)" FT /evidence="ECO:0000269|PubMed:27965258" FT /id="VAR_078800" FT VARIANT 755 FT /note="T -> N (in JRRP; gain-of-function variant resulting FT in spontaneous inflammasome activation; increased FT NLRP1-inflammasome complex assembly)" FT /evidence="ECO:0000269|PubMed:31484767" FT /id="VAR_083844" FT VARIANT 787..843 FT /note="Missing (in MSPC; increased NLRP1-inflammasome FT complex assembly)" FT /evidence="ECO:0000269|PubMed:27662089" FT /id="VAR_078801" FT VARIANT 878 FT /note="T -> M (in dbSNP:rs11657747)" FT /evidence="ECO:0000269|PubMed:11270363" FT /id="VAR_033240" FT VARIANT 1059 FT /note="V -> M (in dbSNP:rs2301582)" FT /id="VAR_024239" FT VARIANT 1069 FT /note="H -> Y (in dbSNP:rs9907167)" FT /id="VAR_033241" FT VARIANT 1119 FT /note="M -> V (no effect on autocatalytic processing, nor FT on IL1B release; dbSNP:rs35596958)" FT /evidence="ECO:0000269|PubMed:11270363, FT ECO:0000269|PubMed:22665479" FT /id="VAR_033242" FT VARIANT 1184 FT /note="M -> V (increased autocatalytic processing and IL1B FT release; dbSNP:rs11651270)" FT /evidence="ECO:0000269|PubMed:11270363, FT ECO:0000269|PubMed:17974005, ECO:0000269|PubMed:22665479" FT /id="VAR_033243" FT VARIANT 1214 FT /note="P -> R (in AIADK; decreased interaction with DPP9, FT leading to increased inflammasome activity; FT dbSNP:rs1057524876)" FT /evidence="ECO:0000269|PubMed:27965258, FT ECO:0000269|PubMed:30291141, ECO:0000269|PubMed:33731932" FT /id="VAR_078802" FT VARIANT 1241 FT /note="V -> L (in dbSNP:rs11653832)" FT /evidence="ECO:0000269|PubMed:11270363" FT /id="VAR_033244" FT VARIANT 1366 FT /note="R -> C (in dbSNP:rs2137722)" FT /evidence="ECO:0000269|PubMed:11270363" FT /id="VAR_020437" FT MUTAGEN 76 FT /note="Q->A: No effect on cleavage by HRV-14 Protease 3C." FT /evidence="ECO:0000269|PubMed:33093214" FT MUTAGEN 85 FT /note="Q->A: No effect on cleavage by HRV-14 Protease 3C." FT /evidence="ECO:0000269|PubMed:33093214" FT MUTAGEN 87 FT /note="Q->A: No effect on cleavage by HRV-14 Protease 3C." FT /evidence="ECO:0000269|PubMed:33093214" FT MUTAGEN 110 FT /note="Q->A: No effect on cleavage by HRV-14 Protease 3C." FT /evidence="ECO:0000269|PubMed:33093214" FT MUTAGEN 130 FT /note="Q->A: Inhibits cleavage by HRV-14 Protease 3C." FT /evidence="ECO:0000269|PubMed:33093214" FT MUTAGEN 130 FT /note="Q->P: Inhibits cleavage by Protease 3C from FT Coxsackievirus B3 and HRV-14." FT /evidence="ECO:0000269|PubMed:33410748" FT MUTAGEN 139 FT /note="Q->A: No effect on cleavage by HRV-14 Protease 3C." FT /evidence="ECO:0000269|PubMed:33093214" FT MUTAGEN 158 FT /note="Q->A: No effect on cleavage by HRV-14 Protease 3C." FT /evidence="ECO:0000269|PubMed:33093214" FT MUTAGEN 171 FT /note="Q->A: No effect on cleavage by HRV-14 Protease 3C." FT /evidence="ECO:0000269|PubMed:33093214" FT MUTAGEN 178..180 FT /note="TST->AAA: In 3A mutant; abolished activation of the FT NLRP1 inflammasome in response to UV-B irradiation and FT ribosome collisions." FT /evidence="ECO:0000269|PubMed:35857590" FT MUTAGEN 191 FT /note="Q->A: No effect on cleavage by HRV-14 Protease 3C." FT /evidence="ECO:0000269|PubMed:33093214" FT MUTAGEN 199 FT /note="Q->A: No effect on cleavage by HRV-14 Protease 3C." FT /evidence="ECO:0000269|PubMed:33093214" FT MUTAGEN 205 FT /note="Q->A: No effect on cleavage by HRV-14 Protease 3C." FT /evidence="ECO:0000269|PubMed:33093214" FT MUTAGEN 333 FT /note="Q->A: Abolished cleavage by the 3C-like proteinase FT nsp5 from human coronavirus SARS-CoV-2." FT /evidence="ECO:0000269|PubMed:35594856" FT MUTAGEN 339..340 FT /note="GK->EA: Loss of ATP binding." FT /evidence="ECO:0000269|PubMed:15212762" FT MUTAGEN 340 FT /note="K->L,S: No effect." FT /evidence="ECO:0000269|PubMed:11076957" FT MUTAGEN 1168 FT /note="H->A: Complete loss of autocatalytic processing and FT of IL1B release. Autocatalytic processing cannot be FT restored by treatment with hydroxylamine." FT /evidence="ECO:0000269|PubMed:22665479" FT MUTAGEN 1186 FT /note="H->A: Complete loss of autocatalytic processing and FT of IL1B release. Autocatalytic processing can be restored FT by treatment with hydroxylamine." FT /evidence="ECO:0000269|PubMed:22665479" FT MUTAGEN 1193..1194 FT /note="LL->EE: Reduced autocatalytic processing and reduced FT interaction with DPP9." FT /evidence="ECO:0000269|PubMed:33731932" FT MUTAGEN 1211 FT /note="S->A: Partial loss of autocatalytic processing and FT of IL1B release." FT /evidence="ECO:0000269|PubMed:22665479" FT MUTAGEN 1212 FT /note="F->A: Complete loss of autocatalytic processing and FT of IL1B release." FT /evidence="ECO:0000269|PubMed:22665479, FT ECO:0000269|PubMed:33093214" FT MUTAGEN 1213 FT /note="S->A: Complete loss of autocatalytic processing and FT of IL1B release. Autocatalytic processing cannot be FT restored by treatment with hydroxylamine. Abolished FT interaction with DPP9. Loss of activation by dsRNA or FT positive-strand RNA virus." FT /evidence="ECO:0000269|PubMed:22087307, FT ECO:0000269|PubMed:22665479, ECO:0000269|PubMed:31525884, FT ECO:0000269|PubMed:32051255, ECO:0000269|PubMed:33243852, FT ECO:0000269|PubMed:33731932" FT MUTAGEN 1213 FT /note="S->C: Complete loss of autocatalytic processing, FT which can be restored by treatment with hydroxylamine." FT /evidence="ECO:0000269|PubMed:22665479" FT MUTAGEN 1214 FT /note="P->A: Partial loss of autocatalytic processing (50%) FT and of IL1B release (50%)." FT /evidence="ECO:0000269|PubMed:22665479" FT MUTAGEN 1240 FT /note="R->D: Slightly reduced formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1249 FT /note="H->A: Complete loss of autocatalytic processing and FT IL1B release. Autocatalytic processing cannot be restored FT by treatment with hydroxylamine." FT /evidence="ECO:0000269|PubMed:22665479" FT MUTAGEN 1260..1261 FT /note="RK->DD: Slightly reduced formation of an FT inflammasome filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1276 FT /note="H->G: Abolished ability to form the NLRP1 FT inflammasome." FT /evidence="ECO:0000269|PubMed:33731932" FT MUTAGEN 1277 FT /note="K->E: Abolished ability to form the NLRP1 FT inflammasome." FT /evidence="ECO:0000269|PubMed:33731932" FT MUTAGEN 1278..1279 FT /note="PP->AG: Abolished formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1278 FT /note="P->E: Impaired ability to form the NLRP1 FT inflammasome." FT /evidence="ECO:0000269|PubMed:33731929" FT MUTAGEN 1281 FT /note="L->E: Impaired ability to form the NLRP1 FT inflammasome." FT /evidence="ECO:0000269|PubMed:33731929" FT MUTAGEN 1320 FT /note="F->A: Slightly reduced formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1322 FT /note="E->R: Abolished ability to form the NLRP1 FT inflammasome." FT /evidence="ECO:0000269|PubMed:33731932" FT MUTAGEN 1383 FT /note="D->R: Abolished formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1386 FT /note="R->D: Abolished formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1387 FT /note="E->R: Does not affect formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1388 FT /note="Q->D: Does not affect formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1392 FT /note="R->D: Abolished formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1392 FT /note="R->E: Impaired ability to induce programmed cell FT death." FT /evidence="ECO:0000269|PubMed:33420033" FT MUTAGEN 1395 FT /note="S->R: Abolished formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1397 FT /note="E->R: Impaired ability to induce programmed cell FT death. Abolished formation of an inflammasome filament FT together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028, FT ECO:0000269|PubMed:33420033" FT MUTAGEN 1401 FT /note="D->R: Impaired ability to induce programmed cell FT death." FT /evidence="ECO:0000269|PubMed:33420033" FT MUTAGEN 1402 FT /note="K->D: Abolished formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1402 FT /note="K->E: Abolished formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1404 FT /note="H->D: Abolished formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1406 FT /note="Q->R: Does not affect formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1410 FT /note="Q->R: Abolished formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1411 FT /note="E->R: Impaired ability to induce programmed cell FT death. Abolished formation of an inflammasome filament FT together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028, FT ECO:0000269|PubMed:33420033" FT MUTAGEN 1413 FT /note="Y->R: Abolished formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1414 FT /note="E->R: Impaired ability to induce programmed cell FT death. Abolished formation of an inflammasome filament FT together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028, FT ECO:0000269|PubMed:33420033" FT MUTAGEN 1415 FT /note="R->D: Abolished formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1420 FT /note="N->E: Abolished formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1422 FT /note="R->E: Abolished formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1427 FT /note="R->D: Abolished formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1427 FT /note="R->E: Impaired ability to induce programmed cell FT death." FT /evidence="ECO:0000269|PubMed:33420033" FT MUTAGEN 1428 FT /note="K->E: Does not affect formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1434 FT /note="Q->R: Does not affect formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1437 FT /note="D->R: Abolished formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1445 FT /note="Y->A: Abolished inflammasome filament formation. FT Impaired ability to induce programmed cell death, but FT retains CAPS1 processing." FT /evidence="ECO:0000269|PubMed:33420033" FT MUTAGEN 1449 FT /note="K->D: Does not affect formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1450 FT /note="E->R: Abolished formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1451 FT /note="T->R: Abolished formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1454 FT /note="H->D: Abolished formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1454 FT /note="H->E: Abolished formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1457 FT /note="M->A: Does not affect ability to induce programmed FT cell death." FT /evidence="ECO:0000269|PubMed:33420033" FT MUTAGEN 1458 FT /note="E->R: Abolished formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028" FT MUTAGEN 1460 FT /note="W->A: Does not affect ability to induce programmed FT cell death." FT /evidence="ECO:0000269|PubMed:33420033" FT MUTAGEN 1461 FT /note="E->R: Does not affect formation of an inflammasome FT filament together with PYCARD/ASC." FT /evidence="ECO:0000269|PubMed:33420028, FT ECO:0000269|PubMed:33420033" FT CONFLICT 287 FT /note="P -> S (in Ref. 7; AAH51787)" FT /evidence="ECO:0000305" FT CONFLICT 782 FT /note="T -> S (in Ref. 1; AAG15254)" FT /evidence="ECO:0000305" FT CONFLICT 995 FT /note="T -> I (in Ref. 1; AAG15254)" FT /evidence="ECO:0000305" FT HELIX 9..15 FT /evidence="ECO:0007829|PDB:1PN5" FT HELIX 18..31 FT /evidence="ECO:0007829|PDB:1PN5" FT HELIX 50..60 FT /evidence="ECO:0007829|PDB:1PN5" FT HELIX 63..77 FT /evidence="ECO:0007829|PDB:1PN5" FT HELIX 80..85 FT /evidence="ECO:0007829|PDB:1PN5" FT STRAND 88..91 FT /evidence="ECO:0007829|PDB:1PN5" FT STRAND 286..288 FT /evidence="ECO:0007829|PDB:7WGE" FT HELIX 300..306 FT /evidence="ECO:0007829|PDB:7WGE" FT HELIX 314..316 FT /evidence="ECO:0007829|PDB:7WGE" FT STRAND 322..324 FT /evidence="ECO:0007829|PDB:7WGE" FT STRAND 328..333 FT /evidence="ECO:0007829|PDB:7WGE" FT TURN 340..342 FT /evidence="ECO:0007829|PDB:7WGE" FT HELIX 343..353 FT /evidence="ECO:0007829|PDB:7WGE" FT TURN 358..360 FT /evidence="ECO:0007829|PDB:7WGE" FT STRAND 362..366 FT /evidence="ECO:0007829|PDB:7WGE" FT HELIX 369..374 FT /evidence="ECO:0007829|PDB:7WGE" FT HELIX 380..387 FT /evidence="ECO:0007829|PDB:7WGE" FT STRAND 389..391 FT /evidence="ECO:0007829|PDB:7WGE" FT HELIX 395..399 FT /evidence="ECO:0007829|PDB:7WGE" FT HELIX 402..404 FT /evidence="ECO:0007829|PDB:7WGE" FT STRAND 405..408 FT /evidence="ECO:0007829|PDB:7WGE" FT STRAND 412..415 FT /evidence="ECO:0007829|PDB:7WGE" FT STRAND 422..425 FT /evidence="ECO:0007829|PDB:7WGE" FT HELIX 436..444 FT /evidence="ECO:0007829|PDB:7WGE" FT STRAND 447..451 FT /evidence="ECO:0007829|PDB:7WGE" FT STRAND 453..457 FT /evidence="ECO:0007829|PDB:7WGE" FT STRAND 459..461 FT /evidence="ECO:0007829|PDB:7WGE" FT TURN 464..466 FT /evidence="ECO:0007829|PDB:7WGE" FT STRAND 474..478 FT /evidence="ECO:0007829|PDB:7WGE" FT HELIX 483..491 FT /evidence="ECO:0007829|PDB:7WGE" FT HELIX 497..509 FT /evidence="ECO:0007829|PDB:7WGE" FT HELIX 511..516 FT /evidence="ECO:0007829|PDB:7WGE" FT HELIX 520..535 FT /evidence="ECO:0007829|PDB:7WGE" FT HELIX 547..558 FT /evidence="ECO:0007829|PDB:7WGE" FT STRAND 559..561 FT /evidence="ECO:0007829|PDB:7WGE" FT HELIX 566..580 FT /evidence="ECO:0007829|PDB:7WGE" FT HELIX 588..593 FT /evidence="ECO:0007829|PDB:7WGE" FT HELIX 598..607 FT /evidence="ECO:0007829|PDB:7WGE" FT STRAND 609..611 FT /evidence="ECO:0007829|PDB:7WGE" FT STRAND 614..617 FT /evidence="ECO:0007829|PDB:7WGE" FT STRAND 619..622 FT /evidence="ECO:0007829|PDB:7WGE" FT HELIX 624..639 FT /evidence="ECO:0007829|PDB:7WGE" FT HELIX 656..659 FT /evidence="ECO:0007829|PDB:7WGE" FT TURN 660..662 FT /evidence="ECO:0007829|PDB:7WGE" FT TURN 665..667 FT /evidence="ECO:0007829|PDB:7WGE" FT HELIX 669..676 FT /evidence="ECO:0007829|PDB:7WGE" FT HELIX 682..689 FT /evidence="ECO:0007829|PDB:7WGE" FT HELIX 698..701 FT /evidence="ECO:0007829|PDB:7WGE" FT HELIX 703..709 FT /evidence="ECO:0007829|PDB:7WGE" FT HELIX 716..723 FT /evidence="ECO:0007829|PDB:7WGE" FT TURN 728..732 FT /evidence="ECO:0007829|PDB:7WGE" FT STRAND 733..735 FT /evidence="ECO:0007829|PDB:7WGE" FT HELIX 748..759 FT /evidence="ECO:0007829|PDB:7WGE" FT STRAND 760..763 FT /evidence="ECO:0007829|PDB:7WGE" FT STRAND 766..770 FT /evidence="ECO:0007829|PDB:7WGE" FT STRAND 783..787 FT /evidence="ECO:0007829|PDB:7WGE" FT HELIX 794..804 FT /evidence="ECO:0007829|PDB:4IM6" FT STRAND 807..809 FT /evidence="ECO:0007829|PDB:5Y3S" FT STRAND 812..814 FT /evidence="ECO:0007829|PDB:4IM6" FT HELIX 822..833 FT /evidence="ECO:0007829|PDB:4IM6" FT STRAND 840..843 FT /evidence="ECO:0007829|PDB:4IM6" FT HELIX 851..862 FT /evidence="ECO:0007829|PDB:4IM6" FT STRAND 869..871 FT /evidence="ECO:0007829|PDB:4IM6" FT HELIX 878..889 FT /evidence="ECO:0007829|PDB:4IM6" FT STRAND 898..900 FT /evidence="ECO:0007829|PDB:4IM6" FT HELIX 908..910 FT /evidence="ECO:0007829|PDB:4IM6" FT HELIX 911..920 FT /evidence="ECO:0007829|PDB:4IM6" FT STRAND 926..928 FT /evidence="ECO:0007829|PDB:4IM6" FT STRAND 931..933 FT /evidence="ECO:0007829|PDB:4IM6" FT HELIX 935..946 FT /evidence="ECO:0007829|PDB:4IM6" FT STRAND 955..957 FT /evidence="ECO:0007829|PDB:4IM6" FT STRAND 961..963 FT /evidence="ECO:0007829|PDB:7WGE" FT HELIX 965..977 FT /evidence="ECO:0007829|PDB:4IM6" FT STRAND 982..984 FT /evidence="ECO:0007829|PDB:4IM6" FT STRAND 1089..1092 FT /evidence="ECO:0007829|PDB:6X6C" FT TURN 1093..1096 FT /evidence="ECO:0007829|PDB:6X6C" FT STRAND 1097..1102 FT /evidence="ECO:0007829|PDB:6X6C" FT STRAND 1104..1106 FT /evidence="ECO:0007829|PDB:6X6C" FT TURN 1111..1113 FT /evidence="ECO:0007829|PDB:6X6C" FT STRAND 1116..1118 FT /evidence="ECO:0007829|PDB:6X6C" FT STRAND 1123..1129 FT /evidence="ECO:0007829|PDB:6X6C" FT HELIX 1132..1138 FT /evidence="ECO:0007829|PDB:6X6C" FT TURN 1142..1144 FT /evidence="ECO:0007829|PDB:6X6C" FT STRAND 1145..1147 FT /evidence="ECO:0007829|PDB:6X6C" FT STRAND 1152..1156 FT /evidence="ECO:0007829|PDB:6X6C" FT STRAND 1163..1166 FT /evidence="ECO:0007829|PDB:6X6C" FT STRAND 1174..1176 FT /evidence="ECO:0007829|PDB:6X6C" FT STRAND 1179..1181 FT /evidence="ECO:0007829|PDB:6X6C" FT STRAND 1184..1188 FT /evidence="ECO:0007829|PDB:6X6C" FT STRAND 1191..1195 FT /evidence="ECO:0007829|PDB:6X6C" FT STRAND 1198..1200 FT /evidence="ECO:0007829|PDB:6X6C" FT STRAND 1218..1220 FT /evidence="ECO:0007829|PDB:6X6C" FT STRAND 1223..1225 FT /evidence="ECO:0007829|PDB:6X6C" FT STRAND 1234..1236 FT /evidence="ECO:0007829|PDB:6X6C" FT STRAND 1241..1253 FT /evidence="ECO:0007829|PDB:6X6C" FT HELIX 1257..1269 FT /evidence="ECO:0007829|PDB:6X6C" FT STRAND 1289..1294 FT /evidence="ECO:0007829|PDB:6X6C" FT STRAND 1305..1308 FT /evidence="ECO:0007829|PDB:6X6C" FT STRAND 1314..1316 FT /evidence="ECO:0007829|PDB:6X6C" FT STRAND 1320..1327 FT /evidence="ECO:0007829|PDB:6X6C" FT STRAND 1333..1338 FT /evidence="ECO:0007829|PDB:6X6C" FT TURN 1339..1341 FT /evidence="ECO:0007829|PDB:6X6C" FT STRAND 1344..1349 FT /evidence="ECO:0007829|PDB:6X6C" FT HELIX 1381..1384 FT /evidence="ECO:0007829|PDB:4IFP" FT HELIX 1386..1392 FT /evidence="ECO:0007829|PDB:4IFP" FT HELIX 1396..1403 FT /evidence="ECO:0007829|PDB:4IFP" FT TURN 1405..1407 FT /evidence="ECO:0007829|PDB:4IFP" FT HELIX 1410..1417 FT /evidence="ECO:0007829|PDB:4IFP" FT STRAND 1419..1421 FT /evidence="ECO:0007829|PDB:4IFP" FT HELIX 1422..1433 FT /evidence="ECO:0007829|PDB:4IFP" FT HELIX 1438..1451 FT /evidence="ECO:0007829|PDB:4IFP" FT HELIX 1453..1462 FT /evidence="ECO:0007829|PDB:4IFP" SQ SEQUENCE 1473 AA; 165866 MW; 438F0DCE45C2562D CRC64; MAGGAWGRLA CYLEFLKKEE LKEFQLLLAN KAHSRSSSGE TPAQPEKTSG MEVASYLVAQ YGEQRAWDLA LHTWEQMGLR SLCAQAQEGA GHSPSFPYSP SEPHLGSPSQ PTSTAVLMPW IHELPAGCTQ GSERRVLRQL PDTSGRRWRE ISASLLYQAL PSSPDHESPS QESPNAPTST AVLGSWGSPP QPSLAPREQE APGTQWPLDE TSGIYYTEIR EREREKSEKG RPPWAAVVGT PPQAHTSLQP HHHPWEPSVR ESLCSTWPWK NEDFNQKFTQ LLLLQRPHPR SQDPLVKRSW PDYVEENRGH LIEIRDLFGP GLDTQEPRIV ILQGAAGIGK STLARQVKEA WGRGQLYGDR FQHVFYFSCR ELAQSKVVSL AELIGKDGTA TPAPIRQILS RPERLLFILD GVDEPGWVLQ EPSSELCLHW SQPQPADALL GSLLGKTILP EASFLITART TALQNLIPSL EQARWVEVLG FSESSRKEYF YRYFTDERQA IRAFRLVKSN KELWALCLVP WVSWLACTCL MQQMKRKEKL TLTSKTTTTL CLHYLAQALQ AQPLGPQLRD LCSLAAEGIW QKKTLFSPDD LRKHGLDGAI ISTFLKMGIL QEHPIPLSYS FIHLCFQEFF AAMSYVLEDE KGRGKHSNCI IDLEKTLEAY GIHGLFGAST TRFLLGLLSD EGEREMENIF HCRLSQGRNL MQWVPSLQLL LQPHSLESLH CLYETRNKTF LTQVMAHFEE MGMCVETDME LLVCTFCIKF SRHVKKLQLI EGRQHRSTWS PTMVVLFRWV PVTDAYWQIL FSVLKVTRNL KELDLSGNSL SHSAVKSLCK TLRRPRCLLE TLRLAGCGLT AEDCKDLAFG LRANQTLTEL DLSFNVLTDA GAKHLCQRLR QPSCKLQRLQ LVSCGLTSDC CQDLASVLSA SPSLKELDLQ QNNLDDVGVR LLCEGLRHPA CKLIRLGLDQ TTLSDEMRQE LRALEQEKPQ LLIFSRRKPS VMTPTEGLDT GEMSNSTSSL KRQRLGSERA ASHVAQANLK LLDVSKIFPI AEIAEESSPE VVPVELLCVP SPASQGDLHT KPLGTDDDFW GPTGPVATEV VDKEKNLYRV HFPVAGSYRW PNTGLCFVMR EAVTVEIEFC VWDQFLGEIN PQHSWMVAGP LLDIKAEPGA VEAVHLPHFV ALQGGHVDTS LFQMAHFKEE GMLLEKPARV ELHHIVLENP SFSPLGVLLK MIHNALRFIP VTSVVLLYHR VHPEEVTFHL YLIPSDCSIR KAIDDLEMKF QFVRIHKPPP LTPLYMGCRY TVSGSGSGML EILPKELELC YRSPGEDQLF SEFYVGHLGS GIRLQVKDKK DETLVWEALV KPGDLMPATT LIPPARIAVP SPLDAPQLLH FVDQYREQLI ARVTSVEVVL DKLHGQVLSQ EQYERVLAEN TRPSQMRKLF SLSQSWDRKC KDGLYQALKE THPHLIMELW EKGSKKGLLP LSS //