NL1B2_MOUSE
ID NL1B2_MOUSE Reviewed; 1177 AA.
AC A1Z198; F6R9S5; Q2LK61; Q2LKV8;
DT 09-DEC-2015, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=NACHT, LRR and PYD domains-containing protein 1b allele 2 {ECO:0000303|PubMed:16429160};
DE EC=3.4.-.- {ECO:0000250|UniProtKB:Q2LKW6};
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:18511561, ECO:0000312|MGI:MGI:3582959};
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] (ISOFORMS 1; 2 AND 3), FUNCTION, TISSUE
RP SPECIFICITY, AND ACTIVITY REGULATION.
RC STRAIN=A/J, C57BL/6J, and I/LnJ;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [4]
RP ACTIVITY REGULATION.
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 [5]
RP FUNCTION, ACTIVITY REGULATION, AND LACK OF RESPONSE TO BACILLUS ANTHRACIS
RP LETHAL TOXIN.
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 [6]
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 [7]
RP ACTIVATION BY TOXOPLASMA GONDII, AND ACTIVITY REGULATION.
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 [8]
RP FUNCTION, ACTIVITY REGULATION, AND LACK OF ACTIVATION BY ANTHRAX LETHAL
RP TOXIN.
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 [9]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=26253422; DOI=10.1186/s12974-015-0367-8;
RA Ydens E., Demon D., Lornet G., De Winter V., Timmerman V., Lamkanfi M.,
RA Janssens S.;
RT "Nlrp6 promotes recovery after peripheral nerve injury independently of
RT inflammasomes.";
RL J. Neuroinflamm. 12:143-143(2015).
RN [10]
RP ACTIVITY REGULATION, AND PROTEOLYTIC CLEAVAGE.
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 [11]
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).
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 (By similarity).
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 (By similarity).
CC Acts as a recognition receptor (PRR): recognizes specific pathogens and
CC other damage-associated signals: in response to pathogen-associated
CC signals, the N-terminal part of Nlrp1b is degraded by the proteasome,
CC releasing the cleaved C-terminal part of the protein (NACHT, LRR and
CC PYD domains-containing protein 1b, C-terminus), which polymerizes to
CC initiate the formation of the inflammasome complex: the inflammasome
CC directly recruits pro-caspase-1 (proCASP1) independently of PYCARD/ASC
CC and promotes caspase-1 (CASP1) activation, which subsequently cleaves
CC and activates inflammatory cytokines IL1B and IL18 and gasdermin-D
CC (GSDMD), leading to pyroptosis (By similarity). Activation of Nlrp1b
CC inflammasome is also required for HMGB1 secretion; the active cytokines
CC and HMGB1 stimulate inflammatory responses (By similarity). Contrary to
CC Nlrp1b allele 1, allele 2 is not activated by Bacillus anthracis lethal
CC toxin (PubMed:16429160, PubMed:21170303, PubMed:24492532).
CC {ECO:0000250|UniProtKB:Q2LKW6, ECO:0000269|PubMed:16429160,
CC ECO:0000269|PubMed:21170303, ECO:0000269|PubMed:24492532}.
CC -!- FUNCTION: [NACHT, LRR and PYD domains-containing protein 1b allele 2]:
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:0000250|UniProtKB:Q2LKW6}.
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. In response to pathogen-associated signals,
CC this part is ubiquitinated by the N-end rule pathway and degraded by
CC the proteasome, releasing the cleaved C-terminal part of the protein,
CC which polymerizes and forms the Nlrp1b inflammasome.
CC {ECO:0000250|UniProtKB:Q2LKW6}.
CC -!- FUNCTION: [NACHT, LRR and PYD domains-containing protein 1b, C-
CC terminus]: Constitutes the active part of the Nlrp1b inflammasome. In
CC absence of pathogens and other damage-associated signals, interacts
CC with the N-terminal part of Nlrp1b (NACHT, LRR and PYD domains-
CC containing protein 1b, N-terminus), preventing activation of the Nlrp1b
CC inflammasome. 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 {ECO:0000250|UniProtKB:Q2LKW6}.
CC -!- ACTIVITY REGULATION: Activated by pathogens and other damage-associated
CC signals: activation promotes ubiquitination and degradation of the N-
CC terminal part, releasing the cleaved C-terminal part of the protein
CC (NACHT, LRR and PYD domains-containing protein 1b, C-terminus), which
CC polymerizes and forms the Nlrp1b inflammasome (By similarity). 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 (By similarity). Nlrp1b inflammasome is
CC activated by Val-boroPro (Talabostat, PT-100), an inhibitor of
CC dipeptidyl peptidases DPP8 and DPP9 (PubMed:31383852). 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). May be activated by Toxoplasma gondii, although at a lower
CC extent than allele 1 (PubMed:24218483). Not activated by cleavage by
CC B.anthracis lethal toxin (LT) endopeptidase (PubMed:16429160,
CC PubMed:21170303, PubMed:24492532, PubMed:31383852). May be activated by
CC muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, in a
CC NOD2-dependent manner (PubMed:18511561). {ECO:0000250|UniProtKB:Q2LKW6,
CC ECO:0000250|UniProtKB:Q9C000, ECO:0000269|PubMed:16429160,
CC ECO:0000269|PubMed:18511561, ECO:0000269|PubMed:21170303,
CC ECO:0000269|PubMed:24218483, ECO:0000269|PubMed:24492532,
CC ECO:0000269|PubMed:31383852}.
CC -!- SUBUNIT: Interacts with DPP9; leading to inhibit activation of the
CC inflammasome (By similarity). 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 (By similarity). Interacts
CC (via LRR repeats) with BCL2 and BCL2L1 (via the loop between motifs BH4
CC and BH3). Interacts with NOD2; this interaction may increase IL1B
CC release (By similarity). Interacts with EIF2AK2/PKR; this interaction
CC requires EIF2AK2 activity, is accompanied by EIF2AK2
CC autophosphorylation and promotes inflammasome assembly in response to
CC B.anthracis lethal toxin (By similarity). 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:Q2LKW6,
CC ECO:0000250|UniProtKB:Q9C000}.
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:0000250|UniProtKB:Q2LKW6}.
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. Homomultimer; forms the Nlrp1b
CC inflammasome polymeric complex, a filament composed of homopolymers of
CC this form in response to pathogens and other damage-associated signals.
CC The Nlrp1b inflammasome polymeric complex directly recruits pro-
CC caspase-1 (proCASP1) independently of PYCARD/ASC. Interacts (via CARD
CC domain) with CASP1 (via CARD domain); leading to CASP1 activation.
CC {ECO:0000250|UniProtKB:Q2LKW6}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q2LKW6}.
CC -!- SUBCELLULAR LOCATION: [NACHT, LRR and PYD domains-containing protein
CC 1b, C-terminus]: Inflammasome {ECO:0000250|UniProtKB:Q2LKW6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=A1Z198-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A1Z198-2; Sequence=VSP_058005;
CC Name=3;
CC IsoId=A1Z198-3; Sequence=VSP_058005, VSP_058006, VSP_058007;
CC -!- TISSUE SPECIFICITY: Widely expressed, including in macrophages and, at
CC lower levels, in the peripheral nervous system, including in the
CC sciatic nerve, Schwann cells, sensory neurons and motor neurons.
CC {ECO:0000269|PubMed:16429160, ECO:0000269|PubMed:23506131,
CC ECO:0000269|PubMed:26253422}.
CC -!- INDUCTION: Up-regulated transiently following acute injury of the
CC sciatic nerve with a peak after 44 hours.
CC {ECO:0000269|PubMed:26253422}.
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:0000250|UniProtKB:Q2LKW6}.
CC -!- DOMAIN: The FIIND (domain with function to find) region is involved in
CC homomerization, but not in CASP1-binding. In allele 1, 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. Both N- and C-terminal
CC fragments remain associated (By similarity). It is not known whether
CC this modification occurs in allele 2 (Probable).
CC {ECO:0000250|UniProtKB:Q2LKW6, ECO:0000305}.
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 2]:
CC Autocatalytically cleaved. Autocatalytic cleavage in FIIND region
CC occurs constitutively, prior to activation signals, and is required for
CC inflammasome activity (IL1B release), possibly by facilitating CASP1
CC binding. Both N- and C-terminal parts remain associated non-covalently.
CC {ECO:0000305|PubMed:31383852}.
CC -!- PTM: [NACHT, LRR and PYD domains-containing protein 1b, N-terminus]:
CC Ubiquitinated by the N-end rule pathway in response to pathogens and
CC other damage-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 1b, C-terminus),
CC which polymerizes and forms the Nlrp1b inflammasome.
CC {ECO:0000250|UniProtKB:Q2LKW6}.
CC -!- POLYMORPHISM: Nlrp1b gene is extremely polymorphic. 5 alleles have been
CC described in 18 inbred strains: 1 (AC Q2LKW6), 2 (this entry), 3 (AC
CC Q2LKV5), 4 (AC Q2LKV2) and 5 (AC Q0GKD5). These alleles define
CC susceptibility to B.anthracis lethal toxin (LT). Alleles 2 (carried by
CC A/J, C57BL/6J and I/LnJ), 3 (AKR/J, NOD/LtJ and SJL/J) or 4 (DBA/2J,
CC P/J and SM/J) are not activated by LT. Alleles 1 (carried by
CC 129S1/SvImJ, BALB/cJ, C3H/HeJ, CBA/J, FVB/NJ, NON/ShiLtJ, NZO
CC (NZO/HlLtJ) and SWR/J strains) and 5 (CAST/EiJ) confer macrophage
CC susceptibility to LT. In susceptible strains, infection by Bacillus
CC anthracis leads to IL1B release, neutrophil recruitment and macrophage
CC pyroptosis. This early inflammatory response confers increased
CC resistance to infection (PubMed:16429160). The sequence shown in this
CC entry is that of allele 2 (PubMed:16429160).
CC {ECO:0000269|PubMed:16429160, ECO:0000303|PubMed:16429160}.
CC -!- MISCELLANEOUS: Three tandem Nrlp1 paralogs, Nrlp1a, Nrlp1b and Nrlp1c,
CC have been identified. Nlrp1c is predicted to be a pseudogene.
CC {ECO:0000269|PubMed:23506131, ECO:0000305|PubMed:16429160}.
CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the NLRP family. {ECO:0000305}.
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DR EMBL; DQ117591; AAZ40517.1; -; mRNA.
DR EMBL; DQ117592; AAZ40518.1; -; mRNA.
DR EMBL; DQ117593; AAZ40519.1; -; mRNA.
DR EMBL; DQ153214; AAZ40529.1; -; mRNA.
DR EMBL; EF158039; ABM45712.1; -; mRNA.
DR EMBL; AL662908; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL663042; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC141354; AAI41355.1; -; mRNA.
DR CCDS; CCDS36210.1; -. [A1Z198-2]
DR CCDS; CCDS48839.1; -. [A1Z198-1]
DR RefSeq; NP_001035786.1; NM_001040696.1. [A1Z198-2]
DR RefSeq; NP_001155886.1; NM_001162414.1. [A1Z198-1]
DR RefSeq; XP_017170187.1; XM_017314698.1. [A1Z198-2]
DR AlphaFoldDB; A1Z198; -.
DR SMR; A1Z198; -.
DR ComplexPortal; CPX-4266; NLRP1b inflammasome, allele-2 variant.
DR STRING; 10090.ENSMUSP00000104155; -.
DR MEROPS; S79.A01; -.
DR iPTMnet; A1Z198; -.
DR jPOST; A1Z198; -.
DR MaxQB; A1Z198; -.
DR PaxDb; A1Z198; -.
DR PRIDE; A1Z198; -.
DR ProteomicsDB; 252969; -. [A1Z198-1]
DR ProteomicsDB; 252970; -. [A1Z198-2]
DR Ensembl; ENSMUST00000094046; ENSMUSP00000091588; ENSMUSG00000070390. [A1Z198-2]
DR Ensembl; ENSMUST00000108514; ENSMUSP00000104154; ENSMUSG00000070390. [A1Z198-1]
DR Ensembl; ENSMUST00000108515; ENSMUSP00000104155; ENSMUSG00000070390. [A1Z198-1]
DR Ensembl; ENSMUST00000108516; ENSMUSP00000104156; ENSMUSG00000070390. [A1Z198-2]
DR Ensembl; ENSMUST00000136493; ENSMUSP00000121155; ENSMUSG00000070390. [A1Z198-3]
DR GeneID; 637515; -.
DR KEGG; mmu:637515; -.
DR UCSC; uc007jxs.1; mouse. [A1Z198-1]
DR UCSC; uc007jxt.1; mouse.
DR CTD; 637515; -.
DR MGI; MGI:3582959; Nlrp1b.
DR VEuPathDB; HostDB:ENSMUSG00000070390; -.
DR eggNOG; ENOG502S4A4; Eukaryota.
DR GeneTree; ENSGT00940000162176; -.
DR InParanoid; A1Z198; -.
DR OMA; XAIDDEE; -.
DR OrthoDB; 114368at2759; -.
DR PhylomeDB; A1Z198; -.
DR TreeFam; TF340267; -.
DR BioGRID-ORCS; 637515; 0 hits in 71 CRISPR screens.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; A1Z198; protein.
DR Bgee; ENSMUSG00000070390; Expressed in jejunum and 19 other tissues.
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:0072558; C:NLRP1 inflammasome complex; ISS: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; ISS:UniProtKB.
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; ISO:MGI.
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; ISS: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; ISS:UniProtKB.
DR GO; GO:0070269; P:pyroptosis; IMP:MGI.
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; 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 Pfam; PF00619; CARD; 1.
DR Pfam; PF13553; FIIND; 1.
DR Pfam; PF13516; LRR_6; 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; PS50837; NACHT; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cytoplasm; Hydrolase; Immunity;
KW Inflammasome; Inflammatory response; Innate immunity; Leucine-rich repeat;
KW Necrosis; Nucleotide-binding; Protease; Reference proteome; Repeat;
KW Ubl conjugation.
FT CHAIN 1..1177
FT /note="NACHT, LRR and PYD domains-containing protein 1b
FT allele 2"
FT /id="PRO_0000435104"
FT CHAIN 1..927
FT /note="NACHT, LRR and PYD domains-containing protein 1b, N-
FT terminus"
FT /evidence="ECO:0000250|UniProtKB:Q2LKW6"
FT /id="PRO_0000452857"
FT CHAIN 928..1177
FT /note="NACHT, LRR and PYD domains-containing protein 1b, C-
FT terminus"
FT /evidence="ECO:0000250|UniProtKB:Q2LKW6"
FT /id="PRO_0000452858"
FT DOMAIN 131..440
FT /note="NACHT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT REPEAT 632..652
FT /note="LRR 1"
FT REPEAT 689..709
FT /note="LRR 2"
FT DOMAIN 794..1077
FT /note="FIIND"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01174"
FT DOMAIN 1087..1170
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 794..927
FT /note="ZU5"
FT /evidence="ECO:0000250|UniProtKB:Q9C000"
FT REGION 928..1077
FT /note="UPA"
FT /evidence="ECO:0000250|UniProtKB:Q9C000"
FT BINDING 137..144
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT SITE 901
FT /note="Trigger for autolytic processing"
FT /evidence="ECO:0000250|UniProtKB:Q9C000"
FT SITE 927..928
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:Q9C000,
FT ECO:0000255|PROSITE-ProRule:PRU01174"
FT VAR_SEQ 1..606
FT /note="MEESQYKQEHNKKVAQDEGQEDKDTIFETIEAIEAKLMELKTNPESTFNYGI
FT FPEVYMNQGEEILYPAWSLKEENLFQTFKSLRLFQKLCPRGSGNLVKKSWYPCVPEEGG
FT HIINIQDLFGPNIGTQKEPQLVIIEGAAGIGKSTLARQVKRAWMEGELYRDHFQHVFFF
FT SCRELAQCKKLSLAELITQGQDVPTAPINQILSHPEKLLFILDGIDEPAWVLADQNPEL
FT CLYWSQTQPVHTLLGSLLGKSILPEASFLLTTRTTALQKFIPSLPQSCQVEVLGFSDFE
FT QEIYIYKYFAKQIFGIKALMMVESNPVLLTLCEVPWVCWLVCNCLKKQMEQGGDVSLTS
FT QTTTAICLKYISLTIPVHHMRTQLRALCSLAAEGIWKRRTLFSESDLCKQGLDEDAVAI
FT FLKTGVLQKQASSLSYSFAHLCLQEFFASMSCILEDSEERHGDMEMDRIVETLVERYGR
FT QNLFEAPTVRFLFGLLSKEGLKEMEKLFSCSLPGKTKLKLLWHILGKSQPHQPPCLGLL
FT HCLYENQDMKLLTHVMHDLQGTIVPDTDDITHTVLQTNVKHLVVRTDMELMVVTFCIQF
FT CSHMRSLQLNMEGQQGYALTAPR -> MEQSQPKKKSRTKVAQHEGQLNLNPTFKTRKR
FT KEVELMKRRPKPEGHLKLGTIPKVHIKQKGETLDPTWSRKRKNLVQKLTNLLLFEKLCS
FT RGSENLIRKSWYSCEEEERGHMIEIQDLFGPNRGTHKKPQLVIIEGAAGIGKSTLARQV
FT KRAWKEGQLYRNHFQHVFFLSCRELAQYEQLSLAELIAQGQEVPTVPIRQILSHPKELL
FT FILDGIDEPAWVLADQNPELCLHWSQRQPVHTLLGSLLGKSILPGASFLLTARTTALQK
FT IIPYVGQPRRVEVLGFSKFEREVYFRKYFVKESDAIAAFRLVVSNPVLLTLCEVPWVCW
FT LVCTCLKKQMEQGGELSLTSQTTTALCLKYLSLTIPGQHMRTQLRALCSLAAEGICQRR
FT TLFSESDLCKQGLAEDAIATFLKIGILQKQASSLSYSFAHLCLQEFFAVMSYILEDSDE
FT RCDGMEFKRTVETLIEVYGRHTLCEEPTVHFLFGLVNEQGMREMKKIFDCKLPLGTELK
FT MLKSTLGNPTYQHHLGLLHCLYESQEEVLLTYVLCNLHLTGPDKNYMEATVSQTNVKHL
FT VIQTDMELMVVTFCIQFCCHVRSLRVNMKGQQGHKLTVAS (in isoform 2 and
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16429160"
FT /id="VSP_058005"
FT VAR_SEQ 666..676
FT /note="WLVECGLTPTY -> CSAVESLEFCT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16429160"
FT /id="VSP_058006"
FT VAR_SEQ 677..1177
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16429160"
FT /id="VSP_058007"
SQ SEQUENCE 1177 AA; 134163 MW; 4E7116B0523AB17C CRC64;
MEESQYKQEH NKKVAQDEGQ EDKDTIFETI EAIEAKLMEL KTNPESTFNY GIFPEVYMNQ
GEEILYPAWS LKEENLFQTF KSLRLFQKLC PRGSGNLVKK SWYPCVPEEG GHIINIQDLF
GPNIGTQKEP QLVIIEGAAG IGKSTLARQV KRAWMEGELY RDHFQHVFFF SCRELAQCKK
LSLAELITQG QDVPTAPINQ ILSHPEKLLF ILDGIDEPAW VLADQNPELC LYWSQTQPVH
TLLGSLLGKS ILPEASFLLT TRTTALQKFI PSLPQSCQVE VLGFSDFEQE IYIYKYFAKQ
IFGIKALMMV ESNPVLLTLC EVPWVCWLVC NCLKKQMEQG GDVSLTSQTT TAICLKYISL
TIPVHHMRTQ LRALCSLAAE GIWKRRTLFS ESDLCKQGLD EDAVAIFLKT GVLQKQASSL
SYSFAHLCLQ EFFASMSCIL EDSEERHGDM EMDRIVETLV ERYGRQNLFE APTVRFLFGL
LSKEGLKEME KLFSCSLPGK TKLKLLWHIL GKSQPHQPPC LGLLHCLYEN QDMKLLTHVM
HDLQGTIVPD TDDITHTVLQ TNVKHLVVRT DMELMVVTFC IQFCSHMRSL QLNMEGQQGY
ALTAPRMVLY RWTPITNASW KILFYNLKFN SNLEGLDLSG NPLSYSAVQY LCDAMIYPGC
QLKTLWLVEC GLTPTYCSLL ASVLSACSSL RELDLQLNDL CDDGVRMLCE GLRNRACNLR
ILRLDLYSLS AQVITELRTL EENNLKLHIS SIWMPQMMVP TENMDEEDIL TSFKQQRQQS
GANPMEILGT EEDFWGPIGP VATEVVYRER NLYRVQLPMA GSYHCPSTRL HFVVTRAVTI
EIEFCAWSQF LDKTPLQQSH MVVGPLFDIK AEQGAVTAVY LPHFVSLKDT KASTFDFKVA
HFQEHGMVLE TPDRVKPGYT VLKNPSFSPM GVVLRIIPAA RHFIPITSIT LIYYRVNQEE
VTLHLYLVPN DCTIQKAIDD EEMKFQFVRI NKPPPVDNLF IGSRYIVSGS ENLEITPKEL
ELCYRSSKEF QLFSEIYVGN MGSEIKLQIK NKKHMKLIWE ALLKPGDLRP ALPRIAQALK
DAPSLLHFMD QHREQLVARV TSVDPLLDKL HGLVLNEESY EAVRAENTNQ DKMRKLFNLS
RSWSRACKDL FYQALKETHP HLVMDLLEKS GGVSLGS
