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},
GN KIAA0926 {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};
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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 Genevisible; Q9C000; HS.
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.
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 NLRP1-
FT 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
//