NL1B1_MOUSE
ID NL1B1_MOUSE Reviewed; 1233 AA.
AC Q2LKW6;
DT 09-DEC-2015, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2006, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=NACHT, LRR and PYD domains-containing protein 1b allele 1 {ECO:0000303|PubMed:16429160};
DE EC=3.4.-.- {ECO:0000305|PubMed:23818853};
DE Contains:
DE RecName: Full=NACHT, LRR and PYD domains-containing protein 1b, C-terminus {ECO:0000305};
DE Short=Nlrp1b1-CT {ECO:0000305};
DE Contains:
DE RecName: Full=NACHT, LRR and PYD domains-containing protein 1b, N-terminus {ECO:0000305};
DE Short=Nlrp1b1-NT {ECO:0000305};
GN Name=Nlrp1b {ECO:0000303|PubMed:19651869};
GN Synonyms=Nalp1b {ECO:0000303|PubMed:16429160};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC STRAIN=129S1/SvImJ, BALB/cJ, C3H/HeJ, CBA/J, FVB/NJ, NON/ShiLtJ, NZO, and
RC SWR/J;
RX PubMed=16429160; DOI=10.1038/ng1724;
RA Boyden E.D., Dietrich W.F.;
RT "Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin.";
RL Nat. Genet. 38:240-244(2006).
RN [2]
RP SUBCELLULAR LOCATION, ACTIVITY REGULATION, ACTIVATION BY ANTHRAX LETHAL
RP TOXIN, AND INFLAMMASOME ASSEMBLY.
RX PubMed=19124602; DOI=10.1128/iai.01032-08;
RA Nour A.M., Yeung Y.G., Santambrogio L., Boyden E.D., Stanley E.R.,
RA Brojatsch J.;
RT "Anthrax lethal toxin triggers the formation of a membrane-associated
RT inflammasome complex in murine macrophages.";
RL Infect. Immun. 77:1262-1271(2009).
RN [3]
RP FUNCTION, INTERACTION WITH CASP1, ACTIVITY REGULATION, HOMOMERIZATION,
RP ACTIVATION BY ANTHRAX LETHAL TOXIN, AND DOMAIN.
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 [4]
RP INHIBITION OF INFLAMMASOME RESPONSE.
RX PubMed=19494813; DOI=10.1038/nature08100;
RA Guarda G., Dostert C., Staehli F., Cabalzar K., Castillo R., Tardivel A.,
RA Schneider P., Tschopp J.;
RT "T cells dampen innate immune responses through inhibition of NLRP1 and
RT NLRP3 inflammasomes.";
RL Nature 460:269-273(2009).
RN [5]
RP FUNCTION, ACTIVITY REGULATION, AND ACTIVATION BY ANTHRAX LETHAL TOXIN.
RX PubMed=19949100; DOI=10.4049/jimmunol.0903114;
RA Terra J.K., Cote C.K., France B., Jenkins A.L., Bozue J.A., Welkos S.L.,
RA LeVine S.M., Bradley K.A.;
RT "Resistance to Bacillus anthracis infection mediated by a lethal toxin
RT sensitive allele of Nalp1b/Nlrp1b.";
RL J. Immunol. 184:17-20(2010).
RN [6]
RP FUNCTION, ACTIVATION BY ANTHRAX LETHAL TOXIN, AND POLYMORPHISM.
RX PubMed=21170303; DOI=10.1371/journal.ppat.1001222;
RA Moayeri M., Crown D., Newman Z.L., Okugawa S., Eckhaus M., Cataisson C.,
RA Liu S., Sastalla I., Leppla S.H.;
RT "Inflammasome sensor Nlrp1b-dependent resistance to anthrax is mediated by
RT caspase-1, IL-1 signaling and neutrophil recruitment.";
RL PLoS Pathog. 6:E1001222-E1001222(2010).
RN [7]
RP FUNCTION, ACTIVITY REGULATION, AND DISRUPTION PHENOTYPE.
RX PubMed=22753929; DOI=10.4049/jimmunol.1201065;
RA Kovarova M., Hesker P.R., Jania L., Nguyen M., Snouwaert J.N., Xiang Z.,
RA Lommatzsch S.E., Huang M.T., Ting J.P., Koller B.H.;
RT "NLRP1-dependent pyroptosis leads to acute lung injury and morbidity in
RT mice.";
RL J. Immunol. 189:2006-2016(2012).
RN [8]
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 [9]
RP FUNCTION, ACTIVITY REGULATION, HOMOMERIZATION, SUBUNIT, AUTOCATALYTIC
RP CLEAVAGE, AND MUTAGENESIS OF VAL-988; ALA-996; VAL-1012; GLN-1014;
RP ASN-1026; 1100-GLU--LYS-1106 AND LYS-1112.
RX PubMed=22536155; DOI=10.1371/journal.ppat.1002659;
RA Frew B.C., Joag V.R., Mogridge J.;
RT "Proteolytic processing of Nlrp1b is required for inflammasome activity.";
RL PLoS Pathog. 8:E1002659-E1002659(2012).
RN [10]
RP TISSUE SPECIFICITY.
RX PubMed=23506131; DOI=10.1186/1471-2164-14-188;
RA Sastalla I., Crown D., Masters S.L., McKenzie A., Leppla S.H., Moayeri M.;
RT "Transcriptional analysis of the three Nlrp1 paralogs in mice.";
RL BMC Genomics 14:188-188(2013).
RN [11]
RP ACTIVITY REGULATION, ACTIVATION BY ANTHRAX LETHAL TOXIN, AND MUTAGENESIS OF
RP 137-GLY--SER-139.
RX PubMed=23230290; DOI=10.1128/iai.01003-12;
RA Liao K.C., Mogridge J.;
RT "Activation of the Nlrp1b inflammasome by reduction of cytosolic ATP.";
RL Infect. Immun. 81:570-579(2013).
RN [12]
RP FUNCTION, ACTIVITY REGULATION, CLEAVAGE BY ANTHRAX LETHAL TOXIN,
RP AUTOCATALYTIC CLEAVAGE, AND MUTAGENESIS OF 34-LYS--ARG-36; 37-PRO--LEU-39;
RP 38-LYS-LEU-39; LEU-43; LYS-44; LEU-45; 626-ARG--LEU-719 AND SER-984.
RX PubMed=23818853; DOI=10.1371/journal.ppat.1003452;
RA Chavarria-Smith J., Vance R.E.;
RT "Direct proteolytic cleavage of NLRP1B is necessary and sufficient for
RT inflammasome activation by anthrax lethal factor.";
RL PLoS Pathog. 9:E1003452-E1003452(2013).
RN [13]
RP ACTIVITY REGULATION, AND ACTIVATION BY TOXOPLASMA GONDII.
RX PubMed=24218483; DOI=10.1128/iai.01170-13;
RA Ewald S.E., Chavarria-Smith J., Boothroyd J.C.;
RT "NLRP1 is an inflammasome sensor for Toxoplasma gondii.";
RL Infect. Immun. 82:460-468(2014).
RN [14]
RP ACTIVITY REGULATION, ACTIVATION BY ANTHRAX LETHAL TOXIN, MUTAGENESIS OF
RP 1-MET--GLU-40; 1-MET--LYS-44; 1-MET--VAL-50; 43-LEU--LEU-45; GLU-629;
RP ASP-632; SER-634; GLN-644; ASN-648; ARG-651; LYS-658; THR-659; TRP-661;
RP VAL-663; LYS-664; ARG-670; SER-673; THR-686; GLU-687; TYR-689; GLN-691;
RP ASP-698; ARG-701; MET-702; GLU-705; ASP-720; GLN-727; GLU-731; THR-734;
RP LYS-738; ILE-744; SER-746; 749-MET--ARG-809 AND 810-MET--ARG-870, AND
RP DOMAIN.
RX PubMed=24935976; DOI=10.1128/iai.02167-14;
RA Neiman-Zenevich J., Liao K.C., Mogridge J.;
RT "Distinct regions of NLRP1B are required to respond to anthrax lethal toxin
RT and metabolic inhibition.";
RL Infect. Immun. 82:3697-3703(2014).
RN [15]
RP FUNCTION, ACTIVITY REGULATION, ACTIVATION BY ANTHRAX LETHAL TOXIN,
RP INFLAMMASOME ASSEMBLY, AND SUBCELLULAR LOCATION.
RX PubMed=24492532; DOI=10.1038/ncomms4209;
RA Van Opdenbosch N., Gurung P., Vande Walle L., Fossoul A., Kanneganti T.D.,
RA Lamkanfi M.;
RT "Activation of the NLRP1b inflammasome independently of ASC-mediated
RT caspase-1 autoproteolysis and speck formation.";
RL Nat. Commun. 5:3209-3209(2014).
RN [16]
RP ACTIVITY REGULATION, AND MUTAGENESIS OF SER-984.
RX PubMed=29396289; DOI=10.1016/j.chembiol.2017.12.013;
RA Okondo M.C., Rao S.D., Taabazuing C.Y., Chui A.J., Poplawski S.E.,
RA Johnson D.C., Bachovchin D.A.;
RT "Inhibition of Dpp8/9 activates the Nlrp1b inflammasome.";
RL Cell Chem. Biol. 25:262-267(2018).
RN [17]
RP INTERACTION WITH DPP8 AND DPP9, ACTIVITY REGULATION, AND MUTAGENESIS OF
RP SER-984.
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 [18]
RP ACTIVITY REGULATION.
RX PubMed=31383852; DOI=10.1038/s41419-019-1817-5;
RA Gai K., Okondo M.C., Rao S.D., Chui A.J., Ball D.P., Johnson D.C.,
RA Bachovchin D.A.;
RT "DPP8/9 inhibitors are universal activators of functional NLRP1 alleles.";
RL Cell Death Dis. 10:587-587(2019).
RN [19]
RP FUNCTION, UBIQUITINATION (NACHT, LRR AND PYD DOMAINS-CONTAINING PROTEIN 1B,
RP N-TERMINUS), AND ACTIVITY REGULATION.
RX PubMed=31268597; DOI=10.15252/embj.2019101996;
RA Xu H., Shi J., Gao H., Liu Y., Yang Z., Shao F., Dong N.;
RT "The N-end rule ubiquitin ligase UBR2 mediates NLRP1B inflammasome
RT activation by anthrax lethal toxin.";
RL EMBO J. 38:e101996-e101996(2019).
RN [20]
RP FUNCTION, UBIQUITINATION (NACHT, LRR AND PYD DOMAINS-CONTAINING PROTEIN 1B,
RP N-TERMINUS), ACTIVITY REGULATION, AND SUBCELLULAR LOCATION.
RX PubMed=30872533; DOI=10.1126/science.aau1330;
RA Sandstrom A., Mitchell P.S., Goers L., Mu E.W., Lesser C.F., Vance R.E.;
RT "Functional degradation: A mechanism of NLRP1 inflammasome activation by
RT diverse pathogen enzymes.";
RL Science 364:0-0(2019).
RN [21]
RP FUNCTION, UBIQUITINATION (NACHT, LRR AND PYD DOMAINS-CONTAINING PROTEIN 1B,
RP N-TERMINUS), AND ACTIVITY REGULATION.
RX PubMed=30872531; DOI=10.1126/science.aau1208;
RA Chui A.J., Okondo M.C., Rao S.D., Gai K., Griswold A.R., Johnson D.C.,
RA Ball D.P., Taabazuing C.Y., Orth E.L., Vittimberga B.A., Bachovchin D.A.;
RT "N-terminal degradation activates the NLRP1B inflammasome.";
RL Science 364:82-85(2019).
RN [22]
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 [23]
RP FUNCTION, AND ACTIVITY REGULATION.
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).
CC -!- FUNCTION: Acts as the sensor component of the Nlrp1b inflammasome,
CC which mediates inflammasome activation in response to various pathogen-
CC associated signals, leading to subsequent pyroptosis (PubMed:19651869,
CC PubMed:21170303, PubMed:22536155, PubMed:22753929, PubMed:23818853).
CC Inflammasomes are supramolecular complexes that assemble in the cytosol
CC in response to pathogens and other damage-associated signals and play
CC critical roles in innate immunity and inflammation (PubMed:19651869,
CC PubMed:21170303, PubMed:22536155, PubMed:22753929, PubMed:23818853,
CC PubMed:31268597, PubMed:30872533, PubMed:30872531). Acts as a
CC recognition receptor (PRR): recognizes specific pathogens and other
CC damage-associated signals, such as B.anthracis lethal toxin (LT) or
CC Val-boroPro inhibitor, and mediates the formation of the inflammasome
CC polymeric complex (PubMed:31268597, PubMed:30872533, PubMed:30872531).
CC In response to pathogen-associated signals, the N-terminal part of
CC Nlrp1b is degraded by the proteasome, releasing the cleaved C-terminal
CC part of the protein (NACHT, LRR and PYD domains-containing protein 1b,
CC C-terminus), which polymerizes to initiate the formation of the
CC inflammasome complex: the inflammasome directly recruits pro-caspase-1
CC (proCASP1) independently of PYCARD/ASC and promotes caspase-1 (CASP1)
CC activation, which subsequently cleaves and activates inflammatory
CC cytokines IL1B and IL18 and gasdermin-D (GSDMD), leading to pyroptosis
CC (PubMed:16429160, PubMed:19949100, PubMed:22753929, PubMed:23818853,
CC PubMed:31268597, PubMed:30872533, PubMed:30872531). Activation of
CC Nlrp1b inflammasome is also required for HMGB1 secretion; the active
CC cytokines and HMGB1 stimulate inflammatory responses (PubMed:22801494).
CC Primary mediator of macrophage susceptibility to B.anthracis LT: in
CC response to B.anthracis infection, macrophages and dendritic cells
CC release IL1B and undergo pyroptosis (PubMed:16429160, PubMed:19949100,
CC PubMed:22753929, PubMed:23818853). This early inflammatory response to
CC the toxin increases resistance to infection by B.anthracis spores
CC (PubMed:16429160, PubMed:19949100, PubMed:22753929, PubMed:23818853).
CC {ECO:0000269|PubMed:16429160, ECO:0000269|PubMed:19651869,
CC ECO:0000269|PubMed:19949100, ECO:0000269|PubMed:21170303,
CC ECO:0000269|PubMed:22536155, ECO:0000269|PubMed:22753929,
CC ECO:0000269|PubMed:22801494, ECO:0000269|PubMed:23818853,
CC ECO:0000269|PubMed:30872531, ECO:0000269|PubMed:30872533,
CC ECO:0000269|PubMed:31268597}.
CC -!- FUNCTION: [NACHT, LRR and PYD domains-containing protein 1b allele 1]:
CC Constitutes the precursor of the Nlrp1b 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:0000305|PubMed:23818853}.
CC -!- FUNCTION: [NACHT, LRR and PYD domains-containing protein 1b, N-
CC terminus]: Regulatory part that prevents formation of the Nlrp1b
CC inflammasome: in absence of pathogens and other damage-associated
CC signals, interacts with the C-terminal part of Nlrp1b (NACHT, LRR and
CC PYD domains-containing protein 1b, C-terminus), preventing activation
CC of the Nlrp1b inflammasome (PubMed:30872533, PubMed:30872531). In
CC response to pathogen-associated signals, this part is ubiquitinated by
CC the N-end rule pathway and degraded by the proteasome, releasing the
CC cleaved C-terminal part of the protein, which polymerizes and forms the
CC Nlrp1b inflammasome (PubMed:30872533, PubMed:30872531).
CC {ECO:0000269|PubMed:30872531, ECO:0000269|PubMed:30872533}.
CC -!- FUNCTION: [NACHT, LRR and PYD domains-containing protein 1b, C-
CC terminus]: Constitutes the active part of the Nlrp1b inflammasome
CC (PubMed:30872533, PubMed:30872531). In absence of pathogens and other
CC damage-associated signals, interacts with the N-terminal part of Nlrp1b
CC (NACHT, LRR and PYD domains-containing protein 1b, N-terminus),
CC preventing activation of the Nlrp1b inflammasome (PubMed:30872533,
CC PubMed:30872531). In response to pathogen-associated signals, the N-
CC terminal part of Nlrp1b is degraded by the proteasome, releasing this
CC form, which polymerizes to form the Nlrp1b inflammasome complex: the
CC Nlrp1b inflammasome complex then directly recruits pro-caspase-1
CC (proCASP1) and promotes caspase-1 (CASP1) activation, leading to
CC gasdermin-D (GSDMD) cleavage and subsequent pyroptosis
CC (PubMed:31268597, PubMed:30872533, PubMed:30872531).
CC {ECO:0000269|PubMed:30872531, ECO:0000269|PubMed:30872533,
CC ECO:0000269|PubMed:31268597}.
CC -!- ACTIVITY REGULATION: Activated by cleavage by B.anthracis lethal toxin
CC (LT) endopeptidase: cleavage by LT promotes ubiquitination and
CC degradation of the N-terminal part, releasing the cleaved C-terminal
CC part of the protein (NACHT, LRR and PYD domains-containing protein 1b,
CC C-terminus), which polymerizes and forms the Nlrp1b inflammasome
CC (PubMed:19124602, PubMed:19651869, PubMed:19949100, PubMed:22536155,
CC PubMed:23818853, PubMed:24492532, PubMed:24935976, PubMed:31383852,
CC PubMed:30872531). Activated by S.flexneri IpaH7.8, an E3 ubiquitin
CC ligase that mediates ubiquitination and degradation of the N-terminal
CC part, releasing the cleaved C-terminal part of the protein, which
CC polymerizes and forms the Nlrp1b inflammasome (PubMed:30872533). Nlrp1b
CC inflammasome is inhibited by DPP8 and DPP9, which sequester the C-
CC terminal fragment of Nlrp1b (NACHT, LRR and PYD domains-containing
CC protein 1b, C-terminus) in a ternary complex, thereby preventing Nlrp1b
CC oligomerization and activation (PubMed:29396289, PubMed:31525884).
CC Nlrp1b inflammasome is activated by Val-boroPro (Talabostat, PT-100),
CC an inhibitor of dipeptidyl peptidases DPP8 and DPP9 (PubMed:29396289,
CC PubMed:31525884, PubMed:31383852, PubMed:30872531). Val-boroPro
CC relieves inhibition of DPP8 and/or DPP9 by promoting disruption of the
CC ternary complex, releasing its C-terminal part from autoinhibition (By
CC similarity). Activated by metabolic inhibitors, such as 2-deoxy-D-
CC glucose and sodium azide, by nutrient deprivation and hypoxia, possibly
CC due to a decrease in cytosolic ATP (PubMed:24935976, PubMed:23230290).
CC Also activated by Toxoplasma gondii (PubMed:24218483). Not activated by
CC muramyl dipeptide, nor by full-length bacterial peptidoglycan
CC (PubMed:22753929). Contrary to its human ortholog, not activated by
CC positive-strand RNA virus such as Semliki Forrest virus or long dsRNA
CC (PubMed:33243852). {ECO:0000250|UniProtKB:Q9C000,
CC ECO:0000269|PubMed:19124602, ECO:0000269|PubMed:19651869,
CC ECO:0000269|PubMed:19949100, ECO:0000269|PubMed:22536155,
CC ECO:0000269|PubMed:22753929, ECO:0000269|PubMed:23230290,
CC ECO:0000269|PubMed:23818853, ECO:0000269|PubMed:24218483,
CC ECO:0000269|PubMed:24492532, ECO:0000269|PubMed:24935976,
CC ECO:0000269|PubMed:29396289, ECO:0000269|PubMed:30872531,
CC ECO:0000269|PubMed:30872533, ECO:0000269|PubMed:31383852,
CC ECO:0000269|PubMed:31525884, ECO:0000269|PubMed:33243852}.
CC -!- SUBUNIT: Interacts with DPP9; leading to inhibit activation of the
CC inflammasome (PubMed:31525884). DPP9 acts via formation of a ternary
CC complex, composed of a DPP9 homodimer, one full-length Nlrp1b protein,
CC and one cleaved C-terminus of Nlrp1b (NACHT, LRR and PYD domains-
CC containing protein 1b, C-terminus) (By similarity). Interacts with
CC DPP8; leading to inhibit activation of the inflammasome, probably via
CC formation of a ternary complex with DPP8 (PubMed:31525884). Interacts
CC (via LRR repeats) with BCL2 and BCL2L1 (via the loop between motifs BH4
CC and BH3) (By similarity). Interacts with NOD2; this interaction may
CC increase IL1B release (By similarity). Interacts with EIF2AK2/PKR; this
CC interaction requires EIF2AK2 activity, is accompanied by EIF2AK2
CC autophosphorylation and promotes inflammasome assembly in response to
CC B.anthracis lethal toxin (PubMed:22801494). Interacts with MEFV; this
CC interaction targets Nlrp1b to degradation by autophagy, hence
CC preventing excessive IL1B- and IL18-mediated inflammation (By
CC similarity). {ECO:0000250|UniProtKB:Q9C000,
CC ECO:0000269|PubMed:22801494, ECO:0000269|PubMed:31525884}.
CC -!- SUBUNIT: [NACHT, LRR and PYD domains-containing protein 1b, N-
CC terminus]: Interacts with the C-terminal part of Nlrp1b (NACHT, LRR and
CC PYD domains-containing protein 1b, C-terminus) in absence of pathogens
CC and other damage-associated signals. {ECO:0000269|PubMed:30872531,
CC ECO:0000269|PubMed:30872533}.
CC -!- SUBUNIT: [NACHT, LRR and PYD domains-containing protein 1b, C-
CC terminus]: Interacts with the N-terminal part of Nlrp1b (NACHT, LRR and
CC PYD domains-containing protein 1b, N-terminus) in absence of pathogens
CC and other damage-associated signals (PubMed:30872533, PubMed:30872531).
CC Homomultimer; forms the Nlrp1b inflammasome polymeric complex, a
CC filament composed of homopolymers of this form in response to pathogens
CC and other damage-associated signals (PubMed:19124602, PubMed:19651869,
CC PubMed:22536155, PubMed:24492532, PubMed:30872533, PubMed:30872531).
CC The Nlrp1b inflammasome polymeric complex directly recruits pro-
CC caspase-1 (proCASP1) independently of PYCARD/ASC (PubMed:19124602,
CC PubMed:19651869, PubMed:24492532). Interacts (via CARD domain) with
CC CASP1 (via CARD domain); leading to CASP1 activation (PubMed:19651869).
CC {ECO:0000269|PubMed:19124602, ECO:0000269|PubMed:19651869,
CC ECO:0000269|PubMed:22536155, ECO:0000269|PubMed:24492532,
CC ECO:0000269|PubMed:30872531, ECO:0000269|PubMed:30872533}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19124602}.
CC Cytoplasm, cytosol {ECO:0000269|PubMed:19124602}. Membrane
CC {ECO:0000269|PubMed:19124602}.
CC -!- SUBCELLULAR LOCATION: [NACHT, LRR and PYD domains-containing protein
CC 1b, C-terminus]: Inflammasome {ECO:0000269|PubMed:24492532,
CC ECO:0000269|PubMed:30872533}.
CC -!- TISSUE SPECIFICITY: Widely expressed, including in macrophages.
CC {ECO:0000269|PubMed:16429160, ECO:0000269|PubMed:23506131}.
CC -!- DOMAIN: The CARD domain is involved in the interaction with CASP1 and
CC CASP4/CASP11. {ECO:0000250|UniProtKB:Q9C000}.
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.
CC {ECO:0000269|PubMed:19651869, ECO:0000269|PubMed:23818853,
CC ECO:0000269|PubMed:24935976}.
CC -!- DOMAIN: The FIIND (domain with function to find) region is involved in
CC homomerization, but not in CASP1-binding (PubMed:22536155).
CC Autocatalytic cleavage in this region occurs constitutively, prior to
CC activation signals, and is required for inflammasome activity (IL1B
CC release), possibly by facilitating CASP1 binding. Both N- and C-
CC terminal fragments remain associated (PubMed:22536155,
CC PubMed:23818853). {ECO:0000269|PubMed:22536155,
CC ECO:0000269|PubMed:23818853}.
CC -!- DOMAIN: [NACHT, LRR and PYD domains-containing protein 1b, C-terminus]:
CC The C-terminal part of Nlrp1b oligomerizes to form the core of the
CC Nlrp1b inflammasome filament: in the filament, the CARD domains form a
CC central helical filaments that are promoted by oligomerized, but
CC flexibly linked, UPA regions surrounding the filaments. The UPA region
CC reduces the threshold needed for filament formation and signaling.
CC {ECO:0000250|UniProtKB:Q9C000}.
CC -!- PTM: [NACHT, LRR and PYD domains-containing protein 1b allele 1]:
CC Autocatalytically cleaved (PubMed:23818853). Autocatalytic cleavage in
CC FIIND region occurs constitutively, prior to activation signals, and is
CC required for inflammasome activity (IL1B release), possibly by
CC facilitating CASP1 binding. Both N- and C-terminal parts remain
CC associated non-covalently (PubMed:23818853).
CC {ECO:0000269|PubMed:23818853}.
CC -!- PTM: [NACHT, LRR and PYD domains-containing protein 1b, N-terminus]:
CC Ubiquitinated by UBR2, a component of the N-end rule pathway in
CC response to pathogens and other damage-associated signals, leading to
CC its degradation by the proteasome and subsequent release of the cleaved
CC C-terminal part of the protein (NACHT, LRR and PYD domains-containing
CC protein 1b, C-terminus), which polymerizes and forms the Nlrp1b
CC inflammasome. {ECO:0000269|PubMed:30872531,
CC ECO:0000269|PubMed:31268597}.
CC -!- PTM: [NACHT, LRR and PYD domains-containing protein 1b, N-terminus]:
CC (Microbial infection) Cleavage by B.anthracis lethal toxin (LT)
CC endopeptidase promotes ubiquitination and degradation of the N-terminal
CC part, releasing the cleaved C-terminal part of the protein (NACHT, LRR
CC and PYD domains-containing protein 1b, C-terminus), which polymerizes
CC and forms the Nlrp1b inflammasome. {ECO:0000269|PubMed:19124602,
CC ECO:0000269|PubMed:19651869, ECO:0000269|PubMed:19949100,
CC ECO:0000269|PubMed:22536155, ECO:0000269|PubMed:23818853,
CC ECO:0000269|PubMed:24492532, ECO:0000269|PubMed:24935976,
CC ECO:0000269|PubMed:30872531}.
CC -!- PTM: [NACHT, LRR and PYD domains-containing protein 1b, N-terminus]:
CC (Microbial infection) Ubiquitinated by S.flexneri IpaH7.8, leading to
CC its degradation by the proteasome and subsequent release of the cleaved
CC C-terminal part of the protein (NACHT, LRR and PYD domains-containing
CC protein 1b, C-terminus), which polymerizes and forms the Nlrp1b
CC inflammasome. {ECO:0000269|PubMed:30872533}.
CC -!- POLYMORPHISM: Nlrp1b gene is extremely polymorphic. 5 alleles have been
CC described in 18 inbred strains: 1 (this entry), 2 (AC A1Z198), 3 (AC
CC Q2LKV5), 4 (AC Q2LKV2) and 5 (AC Q0GKD5). These alleles define
CC susceptibility to B.anthracis lethal toxin (LT). Alleles 1 (carried by
CC strains 129S1/SvImJ, BALB/cJ, C3H/HeJ, CBA/J, FVB/NJ, NON/ShiLtJ, NZO
CC (NZO/HlLtJ) and SWR/J) and 5 (CAST/EiJ) confer macrophage
CC susceptibility to LT. Strains with macrophages resistant to anthrax LT
CC carry alleles 2 (A/J, C57BL/6J and I/LnJ), 3 (AKR/J, NOD/LtJ and SJL/J)
CC or 4 (DBA/2J, P/J and SM/J). Sensitivity to LT leads to IL1B release,
CC macrophage pyroptosis and neutrophil recruitment. This early
CC inflammatory response confers increased resistance to infection by B.
CC anthracis spores (PubMed:16429160, PubMed:19949100, PubMed:21170303).
CC The sequence shown in this entry is that of allele 1 (PubMed:16429160).
CC {ECO:0000269|PubMed:16429160, ECO:0000269|PubMed:19949100,
CC ECO:0000269|PubMed:21170303, ECO:0000303|PubMed:16429160}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype under usual housing
CC conditions. When challenged with intratracheal instillation of
CC B.anthracis lethal toxin (LT), mutant animals are protected from lung
CC damages caused by sustained inflammation. Macrophages isolated from
CC mutant animals are resistant LT. {ECO:0000269|PubMed:22753929}.
CC -!- MISCELLANEOUS: Three tandem Nrlp1 paralogs, Nrlp1a, Nrlp1b and Nrlp1c,
CC have been identified. Nlrp1c is predicted to be a pseudogene. Neither
CC Nlrp1a, nor Nrlp1c are expressed in anthrax lethal toxin susceptible
CC strains, hence neither of them is thought to play an important role in
CC this phenotype. {ECO:0000269|PubMed:23506131,
CC ECO:0000305|PubMed:16429160}.
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:0000269|PubMed:19494813}.
CC -!- SIMILARITY: Belongs to the NLRP family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
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DR EMBL; DQ117583; AAZ40509.1; -; mRNA.
DR EMBL; DQ117584; AAZ40510.1; -; mRNA.
DR EMBL; DQ117585; AAZ40511.1; -; mRNA.
DR EMBL; DQ117586; AAZ40512.1; -; mRNA.
DR EMBL; DQ117587; AAZ40513.1; -; mRNA.
DR EMBL; DQ117588; AAZ40514.1; -; mRNA.
DR EMBL; DQ117589; AAZ40515.1; -; mRNA.
DR EMBL; DQ117590; AAZ40516.1; -; mRNA.
DR AlphaFoldDB; Q2LKW6; -.
DR SMR; Q2LKW6; -.
DR ComplexPortal; CPX-4261; NLRP1b inflammasome, allele-1 variant.
DR IntAct; Q2LKW6; 1.
DR PRIDE; Q2LKW6; -.
DR MGI; MGI:3582959; Nlrp1b.
DR GO; GO:0005737; C:cytoplasm; IC:ComplexPortal.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0061702; C:inflammasome complex; ISO:MGI.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0072558; C:NLRP1 inflammasome complex; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0016887; F:ATP hydrolysis activity; ISO:MGI.
DR GO; GO:0140608; F:cysteine-type endopeptidase activator activity; ISO:MGI.
DR GO; GO:0003690; F:double-stranded DNA binding; ISO:MGI.
DR GO; GO:0003725; F:double-stranded RNA binding; ISO:MGI.
DR GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0043621; F:protein self-association; IDA:UniProtKB.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
DR GO; GO:0140374; P:antiviral innate immune response; ISO:MGI.
DR GO; GO:0051607; P:defense response to virus; ISO:MGI.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0051402; P:neuron apoptotic process; ISO:MGI.
DR GO; GO:1904784; P:NLRP1 inflammasome complex assembly; ISO:MGI.
DR GO; GO:0002221; P:pattern recognition receptor signaling pathway; IC:ComplexPortal.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISO:MGI.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISO:MGI.
DR GO; GO:0030163; P:protein catabolic process; IMP:MGI.
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:0097264; P:self proteolysis; ISO:MGI.
DR CDD; cd08330; CARD_ASC_NALP1; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR001315; CARD.
DR InterPro; IPR033516; CARD8/ASC/NALP1_CARD.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR025307; FIIND_dom.
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 Pfam; PF00619; CARD; 1.
DR Pfam; PF13553; FIIND; 1.
DR Pfam; PF05729; NACHT; 1.
DR Pfam; PF17776; NLRC4_HD2; 1.
DR Pfam; PF17779; NOD2_WH; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50209; CARD; 1.
DR PROSITE; PS51830; FIIND; 1.
DR PROSITE; PS51450; LRR; 2.
DR PROSITE; PS50837; NACHT; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cytoplasm; Hydrolase; Immunity; Inflammasome;
KW Inflammatory response; Innate immunity; Leucine-rich repeat; Membrane;
KW Necrosis; Nucleotide-binding; Protease; Repeat; Ubl conjugation.
FT CHAIN 1..1233
FT /note="NACHT, LRR and PYD domains-containing protein 1b
FT allele 1"
FT /id="PRO_0000435103"
FT CHAIN 1..983
FT /note="NACHT, LRR and PYD domains-containing protein 1b, N-
FT terminus"
FT /evidence="ECO:0000305|PubMed:23818853"
FT /id="PRO_0000452855"
FT CHAIN 984..1233
FT /note="NACHT, LRR and PYD domains-containing protein 1b, C-
FT terminus"
FT /evidence="ECO:0000305|PubMed:23818853"
FT /id="PRO_0000452856"
FT DOMAIN 126..435
FT /note="NACHT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT REPEAT 627..647
FT /note="LRR 1"
FT REPEAT 684..704
FT /note="LRR 2"
FT DOMAIN 850..1133
FT /note="FIIND"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01174"
FT DOMAIN 1143..1226
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 850..983
FT /note="ZU5"
FT /evidence="ECO:0000250|UniProtKB:Q9C000"
FT REGION 984..1133
FT /note="UPA"
FT /evidence="ECO:0000250|UniProtKB:Q9C000"
FT COMPBIAS 8..22
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 132..139
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT SITE 44..45
FT /note="(Microbial infection) Probable cleavage; by anthrax
FT lethal toxin (LT) endopeptidase component"
FT /evidence="ECO:0000305|PubMed:23818853"
FT SITE 957
FT /note="Trigger for autolytic processing"
FT /evidence="ECO:0000250|UniProtKB:Q9C000"
FT SITE 983..984
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01174,
FT ECO:0000269|PubMed:23818853"
FT MUTAGEN 1..50
FT /note="Missing: Low spontaneous IL1B release and loss of
FT activation by LT. Increased IL1B release in response to
FT metabolic inhibitors."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 1..44
FT /note="Missing: Low spontaneous IL1B release and loss of
FT activation by LT. No effect on activation by metabolic
FT inhibitors."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 1..40
FT /note="Missing: No effect on IL1B release."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 34..36
FT /note="KHR->AAA: No effect on cleavage by LT, nor on IL1B
FT processing. No effect on cleavage by LT, nor on IL1B
FT processing; when associated with 38-A-A-39."
FT /evidence="ECO:0000269|PubMed:23818853"
FT MUTAGEN 37..39
FT /note="PKL->QAQ: No effect on cleavage by LT."
FT /evidence="ECO:0000269|PubMed:23818853"
FT MUTAGEN 38..39
FT /note="KL->AA: No effect on cleavage by LT, nor on IL1B
FT processing."
FT /evidence="ECO:0000269|PubMed:23818853"
FT MUTAGEN 43
FT /note="L->Q: Loss of cleavage by LT and of LT-induced IL1B
FT processing and suppression of LT-induced pyroptosis in
FT macrophages, no effect on IL1B release in response to
FT metabolic inhibitors; when associated with A-44 and Q-45."
FT /evidence="ECO:0000269|PubMed:23818853,
FT ECO:0000269|PubMed:24935976"
FT MUTAGEN 44
FT /note="K->A: Partial loss of cleavage by LT and of LT-
FT induced IL1B processing. Loss of cleavage by LT and of LT-
FT induced IL1B processing; when associated with Q-43 and Q-
FT 45. No effect on IL1B release in response to metabolic
FT inhibitors; when associated with Q-43 and Q-45."
FT /evidence="ECO:0000269|PubMed:23818853,
FT ECO:0000269|PubMed:24935976"
FT MUTAGEN 45
FT /note="L->Q: Loss of cleavage by LT and of LT-induced IL1B
FT processing. Loss of cleavage by LT and of LT-induced IL1B
FT processing; when associated with Q-43 and A-44. No effect
FT on IL1B release in response to metabolic inhibitors; when
FT associated with Q-43 and A-44."
FT /evidence="ECO:0000269|PubMed:23818853,
FT ECO:0000269|PubMed:24935976"
FT MUTAGEN 137..139
FT /note="GKS->AAA: Constitutive IL1B release."
FT /evidence="ECO:0000269|PubMed:23230290"
FT MUTAGEN 626..719
FT /note="Missing: Constitutive IL1B processing."
FT /evidence="ECO:0000269|PubMed:23818853"
FT MUTAGEN 629
FT /note="E->A: Increased IL1B release under basal conditions.
FT No effect on IL1B release in response to LT or metabolic
FT inhibitors."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 632
FT /note="D->A: Spontaneous IL1B release under basal
FT conditions, loss of response to metabolic inhibitors and to
FT LT; when associated with A-634."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 634
FT /note="S->A: Spontaneous IL1B release under basal
FT conditions, loss of response to metabolic inhibitors and to
FT LT; when associated with A-632."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 644
FT /note="Q->A: No effect on IL1B release under basal
FT conditions, nor in response to LT or metabolic inhibitors."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 648
FT /note="N->A: No effect on IL1B release under basal
FT conditions, nor in response to LT or metabolic inhibitors."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 651
FT /note="R->A: No effect on IL1B release under basal
FT conditions, nor in response to LT or metabolic inhibitors."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 658
FT /note="K->A: Spontaneous IL1B release under basal
FT conditions, loss of response to metabolic inhibitors and to
FT LT; when associated with A-659."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 659
FT /note="T->A: Spontaneous IL1B release under basal
FT conditions, loss of response to metabolic inhibitors and to
FT LT; when associated with A-658."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 661
FT /note="W->A: No effect on IL1B release under basal
FT conditions, nor in response to LT or metabolic inhibitors."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 663
FT /note="V->A: Spontaneous IL1B release under basal
FT conditions, loss of response to metabolic inhibitors, no
FT effect on the response to LT; when associated with A-664."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 664
FT /note="K->A: Spontaneous IL1B release under basal
FT conditions, loss of response to metabolic inhibitors, no
FT effect on the response to LT; when associated with A-663."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 670
FT /note="R->A: No effect on IL1B release under basal
FT conditions, nor in response to LT or metabolic inhibitors."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 673
FT /note="S->A: No effect on IL1B release under basal
FT conditions, nor in response to LT or metabolic inhibitors."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 686
FT /note="T->A: Spontaneous IL1B release under basal
FT conditions, no effect on the response to metabolic
FT inhibitors, partial loss of response to LT; when associated
FT with A-687."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 687
FT /note="E->A: Spontaneous IL1B release under basal
FT conditions, no effect on the response to metabolic
FT inhibitors, partial loss of response to LT; when associated
FT with A-686."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 689
FT /note="Y->A: No effect on IL1B release under basal
FT conditions, nor in response to LT or metabolic inhibitors."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 691
FT /note="Q->A: Low spontaneous IL1B release, no effect on the
FT response to metabolic inhibitors, nor to LT."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 698
FT /note="D->A: No effect on IL1B release under basal
FT conditions, nor in response to LT or metabolic inhibitors;
FT when associated with A-701 and A-702."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 701
FT /note="R->A: No effect on IL1B release under basal
FT conditions, nor in response to LT or metabolic inhibitors;
FT when associated with A-698 and A-702."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 702
FT /note="M->A: No effect on IL1B release under basal
FT conditions, nor in response to LT or metabolic inhibitors;
FT when associated with A-698 and A-701."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 705
FT /note="E->A: No effect on IL1B release under basal
FT conditions, nor in response to LT or metabolic inhibitors."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 720
FT /note="D->A: Spontaneous IL1B release under basal
FT conditions, loss of response to metabolic inhibitors and to
FT LT."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 727
FT /note="Q->A: No effect on IL1B release under basal
FT conditions, nor in response to LT or metabolic inhibitors."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 731
FT /note="E->A: Increased IL1B release under basal conditions.
FT No effect on IL1B release in response to LT or metabolic
FT inhibitors."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 734
FT /note="T->A: No effect on IL1B release under basal
FT conditions, nor in response to LT or metabolic inhibitors;
FT when associated with A-738."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 738
FT /note="K->A: No effect on IL1B release under basal
FT conditions, nor in response to LT or metabolic inhibitors;
FT when associated with A-734."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 744
FT /note="I->A: Spontaneous IL1B release under basal
FT conditions, loss of response to metabolic inhibitors and to
FT LT; when associated with A-746."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 746
FT /note="S->A: Spontaneous IL1B release under basal
FT conditions, loss of response to metabolic inhibitors and to
FT LT; when associated with A-744."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 749..809
FT /note="Missing: No effect on response to LT, attenuated
FT response to metabolic inhibitors."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 810..870
FT /note="Missing: No effect on response to LT, attenuated
FT response to metabolic inhibitors."
FT /evidence="ECO:0000269|PubMed:24935976"
FT MUTAGEN 984
FT /note="S->A: Loss of autocatalytic cleavage within the
FT FIIND region, abolishing the ability to activate the
FT inflammasome. Abolished interaction with DPP9. No effect on
FT cleavage by LT."
FT /evidence="ECO:0000269|PubMed:23818853,
FT ECO:0000269|PubMed:29396289, ECO:0000269|PubMed:31525884"
FT MUTAGEN 988
FT /note="V->D: Loss of autocatalytic cleavage within the
FT FIIND region and of IL1B release, decrease in CASP1-
FT binding. No effect on homomerization."
FT /evidence="ECO:0000269|PubMed:22536155"
FT MUTAGEN 996
FT /note="A->D: Strong decrease of IL1B release, but no effect
FT on autocatalytic cleavage within the FIIND region."
FT /evidence="ECO:0000269|PubMed:22536155"
FT MUTAGEN 1012
FT /note="V->L: No effect on autocatalytic cleavage within the
FT FIIND region."
FT /evidence="ECO:0000269|PubMed:22536155"
FT MUTAGEN 1014
FT /note="Q->L: No effect on autocatalytic cleavage within the
FT FIIND region."
FT /evidence="ECO:0000269|PubMed:22536155"
FT MUTAGEN 1026
FT /note="N->S: Decrease of IL1B release, but no effect on
FT autocatalytic cleavage within the FIIND region."
FT /evidence="ECO:0000269|PubMed:22536155"
FT MUTAGEN 1100..1106
FT /note="EIKLQIK->AAAAAAA: Loss of homomerization, of
FT autocatalytic cleavage within the FIIND region and of IL1B
FT release. No effect on CASP1-binding."
FT /evidence="ECO:0000269|PubMed:22536155"
FT MUTAGEN 1112
FT /note="K->R: No effect on autocatalytic cleavage within the
FT FIIND region."
FT /evidence="ECO:0000269|PubMed:22536155"
SQ SEQUENCE 1233 AA; 140688 MW; ECB340C9A58BAFCD CRC64;
MEESPPKQKS NTKVAQHEGQ QDLNTTRHMN VELKHRPKLE RHLKLGMIPV VYMKQGEEIL
YPAQSLREEN LIQNFTSLLL LQKLCPKDPE NMIRKSWASC VPEEGGHMIN IQDLFGPNIG
TQKEPQLVII EGAAGIGKST LARLVKRAWK EGQLYRDHFQ HVFFFSCREL AQCKKLSLAE
LIAQGQEVPT APINQILSHP EKLLFILDGI DEPAWVLADQ NPELCLHWSQ RQPVHTLLGS
LLGKSILPEA FFLLTTRTTA LQKFIPSLPM PCQVEVLGFS GIERENYFYK YFANQRHAIT
AFMMVESNPV LLTLCEVPWV CWLVCTCLKK QMEQGRVLSL KSQTTTALCL KYLSLTIPDK
HRRTQVKALC SLAAEGIWKR RTLFSESDLC KQGLDEDAVA TFLKTGVLQK QASSLSYSFA
HLCLQEFFAA ISCILEDSEE RHGNMEMDRI VETLVERYGR QNLFEAPTVR FLFGLLGKEG
VKGMEKLFSC SLHGKTNLKL LWHILVKSQP HQPPCLGLLH CLYENQDMEL LTHVMHDLQG
TIVPGPNDTA HTVLQTNVKH LVVQTDMELM VATFCIQFYC HVRTLQLNME KQQGYALISP
RMVLYRWTPI TNASWEILFY NLKFTRNLEG LDLSGNSLRY SVVQSLCNTL RYPGCQLKTL
WLVKCGLTSR YCSLLASVLS AHSSLTELYL QLNDLGDDGV RMLCEGLRNP VCNLSILWLD
LSSLSAQVIT ELRTLEEKNP KLYIRSIWMP HMMVPTENMD EEAILTTLKQ QRQESGDKPM
EILGTEEDFW GPTGPVATEL VDRVRNLYRM PQMMVPTENM DEEDILTSFK QQRQQSGANP
MEILGTEEDF WGPIGPVATE VVYRERNLYR VQLPMAGSYH CPSTRLHFVV TRAVTIEIEF
CAWSQFLDKT PLQQSHMVVG PLFDIKAEQG AVTAVYLPHF VSLKDTKAST FDFKVAHFQE
HGMVLETPDR VKPGYTVLKN PSFSPMGVVL RIIPAARHFI PITSITLIYY RVNQEEVTLH
LYLVPNDCTI QKAIDDEEMK FQFVRINKPP PVDNLFIGSR YIVSGSENLE ITPKELELCY
RSSKEFQLFS EIYVGNMGSE IKLQIKNKKH MKLIWEALLK PGDLRPALPR IAQALKDAPS
LLHFMDQHRE QLVARVTSVD PLLDKLHGLV LNEESYEAVR AENTNQDKMR KLFNLSRSWS
RACKDLFYQA LKETHPHLVM DLLEKSGGVS LGS
