NLR1A_MOUSE
ID NLR1A_MOUSE Reviewed; 1182 AA.
AC Q2LKU9; M4T3K8; M4T4C8; M4T632; M4TJP5; Q3U0B5; Q67EY4;
DT 09-DEC-2015, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2006, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=NACHT, LRR and PYD domains-containing protein 1a;
DE EC=3.4.-.- {ECO:0000250|UniProtKB:Q9C000};
DE AltName: Full=Caspase recruitment domain-containing protein 7;
DE AltName: Full=Death effector filament-forming ced-4-like apoptosis protein;
DE AltName: Full=Nucleotide-binding domain and caspase recruitment domain;
DE Contains:
DE RecName: Full=NACHT, LRR and PYD domains-containing protein 1a, C-terminus {ECO:0000305};
DE Short=Nlrp1a-CT {ECO:0000250|UniProtKB:Q9C000};
DE Contains:
DE RecName: Full=NACHT, LRR and PYD domains-containing protein 1a, N-terminus {ECO:0000305};
DE Short=Nlrp1a-NT {ECO:0000250|UniProtKB:Q9C000};
GN Name=Nlrp1a {ECO:0000312|MGI:MGI:2684861};
GN Synonyms=Card7, Nalp1, Nalp1a {ECO:0000303|PubMed:16429160}, Nlrp1;
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] (ISOFORM 1).
RC STRAIN=C57BL/6J;
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 [MRNA] (ISOFORM 1), VARIANTS LYS-3; TYR-88; GLY-112;
RP ARG-227; GLU-256; GLN-291; ASN-337; GLY-484; MET-541; HIS-660; ILE-664;
RP ASP-705; ASN-857; SER-975; GLN-1030; PHE-1043; SER-1110 AND ARG-1181, AND
RP TISSUE SPECIFICITY.
RC STRAIN=A/J, AKR/J, CAST/EiJ, DBA/2J, I/LnJ, and PWK/PhJ;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J;
RA Martinon F., Hofmann K., Tschopp J.;
RT "Murine NALPs: a family of proteins involved in inflammation.";
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-488.
RC STRAIN=NOD; TISSUE=Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [6]
RP FUNCTION, INVOLVEMENT IN INFLAMMASOME, TISSUE SPECIFICITY, AND MUTAGENESIS
RP OF GLN-593.
RX PubMed=23219391; DOI=10.1016/j.immuni.2012.08.027;
RA Masters S.L., Gerlic M., Metcalf D., Preston S., Pellegrini M.,
RA O'Donnell J.A., McArthur K., Baldwin T.M., Chevrier S., Nowell C.J.,
RA Cengia L.H., Henley K.J., Collinge J.E., Kastner D.L., Feigenbaum L.,
RA Hilton D.J., Alexander W.S., Kile B.T., Croker B.A.;
RT "NLRP1 inflammasome activation induces pyroptosis of hematopoietic
RT progenitor cells.";
RL Immunity 37:1009-1023(2012).
RN [7]
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).
CC -!- FUNCTION: Acts as the sensor component of the Nlrp1a inflammasome,
CC which mediates inflammasome activation in response to various pathogen-
CC associated signals, leading to subsequent pyroptosis (PubMed:23219391).
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, and mediates the formation of the
CC inflammasome polymeric complex (By similarity). In response to
CC pathogen-associated signals, the N-terminal part of Nlrp1a is degraded
CC by the proteasome, releasing the cleaved C-terminal part of the protein
CC (NACHT, LRR and PYD domains-containing protein 1a, C-terminus), which
CC polymerizes to initiate the formation of the inflammasome complex: the
CC inflammasome recruits pro-caspase-1 (proCASP1) and promotes caspase-1
CC (CASP1) activation, which subsequently cleaves and activates
CC inflammatory cytokines IL1B and IL18 and gasdermin-D (GSDMD), leading
CC to pyroptosis (By similarity). Activation of Nlrp1a inflammasome is
CC also required for HMGB1 secretion; the active cytokines and HMGB1
CC stimulate inflammatory responses (By similarity). When activated in the
CC bone marrow, induces the pyroptosis of hematopoietic stem cells and
CC progenitor cells of both myeloid and lymphoid lineages, hence allowing
CC the removal of damaged cells, and the release of IL1B, which induces
CC granulopoiesis (PubMed:23219391). {ECO:0000250|UniProtKB:Q9C000,
CC ECO:0000269|PubMed:23219391}.
CC -!- FUNCTION: [NACHT, LRR and PYD domains-containing protein 1a]:
CC Constitutes the precursor of the Nlrp1a 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:Q9C000}.
CC -!- FUNCTION: [NACHT, LRR and PYD domains-containing protein 1a, N-
CC terminus]: Regulatory part that prevents formation of the Nlrp1a
CC inflammasome: in absence of pathogens and other damage-associated
CC signals, interacts with the C-terminal part of Nlrp1a (NACHT, LRR and
CC PYD domains-containing protein 1a, C-terminus), preventing activation
CC of the Nlrp1a inflammasome (By similarity). 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 Nlrp1a inflammasome (By similarity).
CC {ECO:0000250|UniProtKB:Q9C000}.
CC -!- FUNCTION: [NACHT, LRR and PYD domains-containing protein 1a, C-
CC terminus]: Constitutes the active part of the Nlrp1a inflammasome (By
CC similarity). In absence of pathogens and other damage-associated
CC signals, interacts with the N-terminal part of Nlrp1a (NACHT, LRR and
CC PYD domains-containing protein 1a, N-terminus), preventing activation
CC of the Nlrp1a inflammasome (By similarity). In response to pathogen-
CC associated signals, the N-terminal part of Nlrp1a is degraded by the
CC proteasome, releasing this form, which polymerizes to form the Nlrp1a
CC inflammasome complex: the Nlrp1a inflammasome complex then directly
CC recruits pro-caspase-1 (proCASP1) and promotes caspase-1 (CASP1)
CC activation, leading to gasdermin-D (GSDMD) cleavage and subsequent
CC pyroptosis (By similarity). {ECO:0000250|UniProtKB:Q9C000}.
CC -!- ACTIVITY REGULATION: Nlrp1a inflammasome is activated by pathogens and
CC other damage-associated signals: activation 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 1a,
CC C-terminus), which polymerizes and forms the Nlrp1a inflammasome (By
CC similarity). Nlrp1a inflammasome is inhibited by DPP8 and DPP9, which
CC sequester the C-terminal fragment of Nlrp1a (NACHT, LRR and PYD
CC domains-containing protein 1a, C-terminus) in a ternary complex,
CC thereby preventing Nlrp1a oligomerization and activation (By
CC similarity). Nlrp1a inflammasome is activated by Val-boroPro
CC (Talabostat, PT-100), an inhibitor of dipeptidyl peptidases DPP8 and
CC DPP9 (PubMed:31383852). Val-boroPro relieves inhibition of DPP8 and/or
CC DPP9 by promoting disruption of the ternary complex, releasing its C-
CC terminal part from autoinhibition (By similarity).
CC {ECO:0000250|UniProtKB:Q2LKW6, ECO:0000250|UniProtKB:Q9C000,
CC ECO:0000269|PubMed:31383852}.
CC -!- SUBUNIT: Interacts (via LRR repeats) with BCL2 and BCL2L1 (via the loop
CC between motifs BH4 and BH3) (By similarity). Interacts with NOD2; this
CC interaction is enhanced in the presence of muramyl dipeptide (MDP) and
CC increases IL1B release (By similarity). Interacts with EIF2AK2/PKR;
CC this interaction requires EIF2AK2 activity, is accompanied by EIF2AK2
CC autophosphorylation and promotes inflammasome assembly in response to
CC danger-associated signals (By similarity). Interacts with MEFV; this
CC interaction targets Nlrp1a to degradation by autophagy, hence
CC preventing excessive IL1B- and IL18-mediated inflammation (By
CC similarity). 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 Nlrp1a protein,
CC and one cleaved C-terminus of Nlrp1a (NACHT, LRR and PYD domains-
CC containing protein 1a, 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).
CC {ECO:0000250|UniProtKB:Q9C000}.
CC -!- SUBUNIT: [NACHT, LRR and PYD domains-containing protein 1a, N-
CC terminus]: Interacts with the C-terminal part of Nlrp1a (NACHT, LRR and
CC PYD domains-containing protein 1a, C-terminus) in absence of pathogens
CC and other damage-associated signals. {ECO:0000250|UniProtKB:Q9C000}.
CC -!- SUBUNIT: [NACHT, LRR and PYD domains-containing protein 1a, C-
CC terminus]: Interacts with the N-terminal part of Nlrp1a (NACHT, LRR and
CC PYD domains-containing protein 1a, N-terminus) in absence of pathogens
CC and other damage-associated signals (By similarity). Homomultimer;
CC forms the Nlrp1a inflammasome polymeric complex, a filament composed of
CC homopolymers of this form in response to pathogens and other damage-
CC associated signals (By similarity). Interacts (via CARD domain) with
CC CASP1 (via CARD domain); leading to CASP1 activation (By similarity).
CC {ECO:0000250|UniProtKB:Q9C000}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q9C000}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9C000}. Nucleus {ECO:0000250|UniProtKB:Q9C000}.
CC Note=Nucleocytoplasmic distribution in lymphoid organs (probably in T-
CC cells) and in neurons. In epithelial cells, predominantly cytoplasmic.
CC {ECO:0000250|UniProtKB:Q9C000}.
CC -!- SUBCELLULAR LOCATION: [NACHT, LRR and PYD domains-containing protein
CC 1a, C-terminus]: Inflammasome {ECO:0000250|UniProtKB:Q9C000}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q2LKU9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q2LKU9-2; Sequence=VSP_058002, VSP_058003, VSP_058004;
CC -!- TISSUE SPECIFICITY: Highly expressed in hematopoietic stem cells and
CC progenitor cells of both myeloid and lymphoid origin (PubMed:23219391).
CC The expression is highly strain-dependent. Not expressed in Balb/cJ
CC animals, but widely expressed in C57BL/6J. Expressed in macrophages
CC resistant to Bacillus anthracis lethal toxin, but not in toxin-
CC sensitive macrophages, except in CAST/EiJ strain (PubMed:23506131).
CC {ECO:0000269|PubMed:23219391, ECO:0000269|PubMed:23506131}.
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. Autocatalytic cleavage in
CC this 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 fragments remain
CC associated. {ECO:0000250|UniProtKB:Q2LKW6}.
CC -!- DOMAIN: [NACHT, LRR and PYD domains-containing protein 1a, C-terminus]:
CC The C-terminal part of Nlrp1a oligomerizes to form the core of the
CC Nlrp1a 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 1a]:
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 1a, N-terminus]:
CC Ubiquitinated in response to pathogen-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 1a, C-terminus), which polymerizes and forms the Nlrp1a
CC inflammasome. {ECO:0000250|UniProtKB:Q9C000}.
CC -!- MISCELLANEOUS: Three tandem Nrlp1 paralogs, Nrlp1a, Nrlp1b and Nrlp1c,
CC are present in at least 2 strains, C57BL/6J and 129S1/SvImJ. Nlrp1c is
CC predicted to be a pseudogene. Nlrp1b is the primary mediator of
CC macrophage susceptibility to Bacillus anthracis lethal toxin (LT).
CC Neither Nlrp1a, nor Nrlp1c are expressed in anthrax lethal toxin
CC susceptible strains, hence neither of them is thought to play an
CC important role in this phenotype. {ECO:0000269|PubMed:23506131,
CC ECO:0000305|PubMed:16429160}.
CC -!- SIMILARITY: Belongs to the NLRP family. {ECO:0000305}.
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DR EMBL; DQ117601; AAZ40527.1; -; mRNA.
DR EMBL; KC539856; AGH68332.1; -; mRNA.
DR EMBL; KC539857; AGH68333.1; -; mRNA.
DR EMBL; KC539858; AGH68334.1; -; mRNA.
DR EMBL; KC539859; AGH68335.1; -; mRNA.
DR EMBL; KC539860; AGH68336.1; -; mRNA.
DR EMBL; KC539861; AGH68337.1; -; mRNA.
DR EMBL; AY355339; AAR14736.1; -; mRNA.
DR EMBL; AL596136; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL662908; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK157034; BAE33940.1; -; mRNA.
DR CCDS; CCDS48838.1; -. [Q2LKU9-1]
DR RefSeq; NP_001004142.2; NM_001004142.2. [Q2LKU9-1]
DR RefSeq; XP_017169843.1; XM_017314354.1. [Q2LKU9-1]
DR RefSeq; XP_017169844.1; XM_017314355.1. [Q2LKU9-1]
DR AlphaFoldDB; Q2LKU9; -.
DR SMR; Q2LKU9; -.
DR ComplexPortal; CPX-4271; NLRP1a inflammasome.
DR STRING; 10090.ENSMUSP00000104158; -.
DR MEROPS; S79.A02; -.
DR iPTMnet; Q2LKU9; -.
DR PhosphoSitePlus; Q2LKU9; -.
DR EPD; Q2LKU9; -.
DR MaxQB; Q2LKU9; -.
DR PaxDb; Q2LKU9; -.
DR PRIDE; Q2LKU9; -.
DR ProteomicsDB; 252904; -. [Q2LKU9-1]
DR ProteomicsDB; 252905; -. [Q2LKU9-2]
DR Ensembl; ENSMUST00000048514; ENSMUSP00000038186; ENSMUSG00000069830. [Q2LKU9-2]
DR Ensembl; ENSMUST00000108518; ENSMUSP00000104158; ENSMUSG00000069830. [Q2LKU9-1]
DR GeneID; 195046; -.
DR KEGG; mmu:195046; -.
DR UCSC; uc007jxq.2; mouse. [Q2LKU9-1]
DR UCSC; uc011xyf.1; mouse.
DR CTD; 195046; -.
DR MGI; MGI:2684861; Nlrp1a.
DR VEuPathDB; HostDB:ENSMUSG00000069830; -.
DR eggNOG; ENOG502S4A4; Eukaryota.
DR GeneTree; ENSGT00940000162176; -.
DR HOGENOM; CLU_002274_2_4_1; -.
DR OMA; VELWEKW; -.
DR OrthoDB; 114368at2759; -.
DR TreeFam; TF340267; -.
DR Reactome; R-MMU-844455; The NLRP1 inflammasome.
DR BioGRID-ORCS; 195046; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Nlrp1a; mouse.
DR PRO; PR:Q2LKU9; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q2LKU9; protein.
DR Bgee; ENSMUSG00000069830; Expressed in granulocyte and 13 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; ISS:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; ISS:HGNC-UCL.
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; ISS:HGNC-UCL.
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; ISS:HGNC-UCL.
DR GO; GO:0140374; P:antiviral innate immune response; ISO:MGI.
DR GO; GO:0042742; P:defense response to bacterium; IDA: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; ISS:HGNC-UCL.
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; IDA:BHF-UCL.
DR GO; GO:0097300; P:programmed necrotic cell death; IDA:MGI.
DR GO; GO:0051260; P:protein homooligomerization; ISS:UniProtKB.
DR GO; GO:0070269; P:pyroptosis; ISO:MGI.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro.
DR GO; GO:0032495; P:response to muramyl dipeptide; IDA:BHF-UCL.
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; PS51450; LRR; 3.
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; Nucleus; Protease; Reference proteome;
KW Repeat; Ubl conjugation.
FT CHAIN 1..1182
FT /note="NACHT, LRR and PYD domains-containing protein 1a"
FT /id="PRO_0000435102"
FT CHAIN 1..932
FT /note="NACHT, LRR and PYD domains-containing protein 1a, N-
FT terminus"
FT /evidence="ECO:0000250|UniProtKB:Q9C000"
FT /id="PRO_0000452853"
FT CHAIN 933..1182
FT /note="NACHT, LRR and PYD domains-containing protein 1a, C-
FT terminus"
FT /evidence="ECO:0000250|UniProtKB:Q9C000"
FT /id="PRO_0000452854"
FT DOMAIN 133..442
FT /note="NACHT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT REPEAT 634..655
FT /note="LRR 1"
FT REPEAT 691..711
FT /note="LRR 2"
FT REPEAT 720..743
FT /note="LRR 3"
FT DOMAIN 799..1082
FT /note="FIIND"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01174"
FT DOMAIN 1092..1175
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 780..806
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 799..932
FT /note="ZU5"
FT /evidence="ECO:0000250|UniProtKB:Q9C000"
FT REGION 933..1082
FT /note="UPA"
FT /evidence="ECO:0000250|UniProtKB:Q9C000"
FT BINDING 139..146
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT SITE 906
FT /note="Trigger for autolytic processing"
FT /evidence="ECO:0000250|UniProtKB:Q9C000"
FT SITE 932..933
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:Q9C000,
FT ECO:0000255|PROSITE-ProRule:PRU01174"
FT VAR_SEQ 668
FT /note="W -> CTLPEDMNKAEVKNTEAKGSLGEKAPGPRNDIFPFPPAHCPYNQTST
FT SEHLPCR (in isoform 2)"
FT /id="VSP_058002"
FT VAR_SEQ 785
FT /note="S -> SGMVGWLLKEDNVKKIKQNATNTYAHTHTHTHAELVPLKTFHPCSPV
FT SP (in isoform 2)"
FT /id="VSP_058003"
FT VAR_SEQ 1072..1085
FT /note="DLRPALPKIATAPK -> KISLRPETLRVEERDTKGAFLCSFPVSSLSL
FT (in isoform 2)"
FT /id="VSP_058004"
FT VARIANT 3
FT /note="E -> K (in strain: CAST/EiJ)"
FT /evidence="ECO:0000269|PubMed:23506131"
FT VARIANT 88
FT /note="F -> Y (in strain: PWK/PhJ)"
FT /evidence="ECO:0000269|PubMed:23506131"
FT VARIANT 112
FT /note="E -> G (in strain: CAST/EiJ, DBA/2J and PWK/PhJ)"
FT /evidence="ECO:0000269|PubMed:23506131"
FT VARIANT 227
FT /note="Q -> R (in strain: PWK/PhJ)"
FT /evidence="ECO:0000269|PubMed:23506131"
FT VARIANT 256
FT /note="G -> E (in strain: CAST/EiJ, DBA/2J and PWK/PhJ)"
FT /evidence="ECO:0000269|PubMed:23506131"
FT VARIANT 291
FT /note="R -> Q (in strain: DBA/2J)"
FT /evidence="ECO:0000269|PubMed:23506131"
FT VARIANT 337
FT /note="K -> N (in strain: PWK/PhJ)"
FT /evidence="ECO:0000269|PubMed:23506131"
FT VARIANT 484
FT /note="S -> G (in strain: DBA/2J and CAST/EiJ)"
FT /evidence="ECO:0000269|PubMed:23506131"
FT VARIANT 541
FT /note="V -> M (in strain: PWK/PhJ)"
FT /evidence="ECO:0000269|PubMed:23506131"
FT VARIANT 660
FT /note="R -> H (in strain: AKR/J)"
FT /evidence="ECO:0000269|PubMed:23506131"
FT VARIANT 664
FT /note="L -> I (in strain: PWK/PhJ)"
FT /evidence="ECO:0000269|PubMed:23506131"
FT VARIANT 705
FT /note="G -> D (in strain: DBA/2J)"
FT /evidence="ECO:0000269|PubMed:23506131"
FT VARIANT 857
FT /note="D -> N (in strain: PWK/PhJ)"
FT /evidence="ECO:0000269|PubMed:23506131"
FT VARIANT 975
FT /note="N -> S (in strain: PWK/PhJ)"
FT /evidence="ECO:0000269|PubMed:23506131"
FT VARIANT 1030
FT /note="R -> Q (in strain: DBA/2J)"
FT /evidence="ECO:0000269|PubMed:23506131"
FT VARIANT 1043
FT /note="I -> F (in strain: CAST/EiJ)"
FT /evidence="ECO:0000269|PubMed:23506131"
FT VARIANT 1110
FT /note="P -> S (in strain: DBA/2J)"
FT /evidence="ECO:0000269|PubMed:23506131"
FT VARIANT 1181
FT /note="K -> R (in strain: CAST/EiJ and DBA/2J)"
FT /evidence="ECO:0000269|PubMed:23506131"
FT MUTAGEN 593
FT /note="Q->P: Constitutively active in IL1B release. In
FT conventional housing conditions, mice bearing this mutation
FT develop a systemic inflammatory phenotype associated with
FT elevated IL1B and IL18 levels at 3-5 months of age. In a
FT germ-free environment, they exhibit neutrophilia and
FT myocarditis."
FT /evidence="ECO:0000269|PubMed:23219391"
FT CONFLICT 228
FT /note="N -> D (in Ref. 5; BAE33940)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1182 AA; 134308 MW; D6D3F9FD5629D44A CRC64;
MEESQSKQES STKVAQHEGQ EDVDPTFKTK KLMEVELMKH RVQLERNLKL RTFPGARTKQ
VKEALYPLLT WSSKSKNLFQ NFTKLLLFKK LCQRGSENLV RESWYPCVPE EEAHMIDIQD
LFGPNLGTQK KPQLVIIEGA AGIGKSTLAR LVKRAWKEGK LYRNDFHHVF FFSCRELAQY
EQLSLAELIV QGQEVPTAPI RQILSHPEKL LFILDGIDEP AWVLADQNPE LCLHWSQTQP
VHTLLGSLLG KSILPGASFL LTTRTTALQK FIPSLEQPCQ VEVLGFTLFE RKNYFYKYFG
KKKGGVTTFT LVKSNSALLT LCEVPWVCWL VCTCLKKQME QGGELSLTSQ TTTALCLKYL
SLTIPGQHMR TQLRDLCSLA AEGVCQRRTL FSESDLCKQG LDEHAIASFL KIGVLQKQAS
SLSYSFAHLC LQEFFAAMSY ILDDSEERHA DMKNDRIVET LVERYGRQNL FEAPTVRFLF
GLLSKEELKK IEKLFSCSLH GKTKLKLLWH ILGKSQPHQP PCLGLLHCLY ENQDMELLTH
VMHDLQGTIV PGPDDLAHTV LQTNVKHLVI QTDMDLMVVT FCIKFCCHVR SLQLNRKVQQ
GHKFTAPGMV LYRWTPITDA SWKIFFSNLK LARNLEELDL SGNPLSYYAV HSLCTTLRKR
GCQLKTLWLV ECGLTSTYCS LLASVLSARS SLTELDLQLN DLGDGGVKML CEGLRNPACN
LSILWLDQAS LSDQVIAELR TLEAKNPKLL ISSTWKPHVM VPTMNMDKEE VGDSQALLKQ
QRQQSGDKHM EPLGTEDEFW GPTGPVTTEV VDRERNLYRV QLPMAGSYHC PSTGLHFVVT
RAVTIEIEFC AWSQYLDKTP LQQSHMVVGP LFDIKAEQGA VTAVYLPHFV ALQEGIVDSS
LFHVAHFQEH GMVLETPARV EQHYAVLENP SFSPMGILLR MIPAVGHFIP ITSTTLIYYH
LYLEDVTFHL YLVPNDCSIR KAIDDEEMKF QFVRINKPPP VDALYLGSRY IVSSSKLVEI
IPKELELCYR SPGESQLFSE IDIGHMDSEI KLQIKDKRHM NLKWEALLKP GDLRPALPKI
ATAPKDAPSL LHFMDQHREQ LVARVTSVDP LLDKLHGLVL SEDSYEVVRS ETTNQDKMRK
LFSLSRSWSW DCKDQFYQAL KETHPHLVMD ILEKLGGVSV KS
