NL1A1_RAT
ID NL1A1_RAT Reviewed; 1218 AA.
AC D9I2F9; A0A0G2QC28; F1LPA5;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 1.
DT 03-AUG-2022, entry version 87.
DE RecName: Full=NACHT, LRR and PYD domains-containing protein 1a allele 1 {ECO:0000305};
DE EC=3.4.-.- {ECO:0000250|UniProtKB:Q9C000};
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|RGD:1310963};
GN Synonyms=Nlrp1 {ECO:0000303|PubMed:20502689};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ACTIVITY REGULATION, AND PROTEOLYTIC
RP CLEAVAGE BY ANTHRAX LETHAL TOXIN.
RC STRAIN=BN-lx {ECO:0000312|EMBL:ADI96226.1},
RC Brown Norway {ECO:0000312|EMBL:ADI96225.1},
RC Dahl salt-sensitive {ECO:0000312|EMBL:ADI96228.1},
RC Sprague-Dawley {ECO:0000312|EMBL:ADI96231.1}, and
RC Wistar {ECO:0000312|EMBL:ADI96234.1};
RX PubMed=20502689; DOI=10.1371/journal.ppat.1000906;
RA Newman Z.L., Printz M.P., Liu S., Crown D., Breen L., Miller-Randolph S.,
RA Flodman P., Leppla S.H., Moayeri M.;
RT "Susceptibility to anthrax lethal toxin-induced rat death is controlled by
RT a single chromosome 10 locus that includes rNlrp1.";
RL PLoS Pathog. 6:e1000906-e1000906(2010).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [3]
RP FUNCTION, AND 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 [4]
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 [5] {ECO:0007744|PDB:7CRV, ECO:0007744|PDB:7CRW}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 783-968 AND 969-1122 IN COMPLEX
RP WITH DPP9, FUNCTION, PROTEOLYTIC CLEAVAGE, ACTIVITY REGULATION, AND
RP MUTAGENESIS OF HIS-942 AND SER-969.
RX PubMed=33731929; DOI=10.1038/s41586-021-03320-w;
RA Huang M., Zhang X., Toh G.A., Gong Q., Wang J., Han Z., Wu B., Zhong F.,
RA Chai J.;
RT "Structural and biochemical mechanisms of NLRP1 inhibition by DPP9.";
RL Nature 592:773-777(2021).
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:33731929).
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, such as B.anthracis lethal toxin (LT)
CC or Val-boroPro inhibitor, and mediates the formation of the
CC inflammasome polymeric complex (PubMed:20502689, PubMed:31383852,
CC PubMed:33731929). In response to pathogen-associated signals, the N-
CC terminal part of Nlrp1a is degraded by the proteasome, releasing the
CC cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-
CC containing protein 1a, C-terminus), which polymerizes to initiate the
CC formation of the inflammasome complex: the inflammasome directly
CC recruits pro-caspase-1 (proCASP1) independently of PYCARD/ASC and
CC promotes caspase-1 (CASP1) activation, which subsequently cleaves and
CC activates inflammatory cytokines IL1B and IL18 and gasdermin-D (GSDMD),
CC leading to pyroptosis (By similarity). {ECO:0000250|UniProtKB:Q2LKU9,
CC ECO:0000250|UniProtKB:Q2LKW6, ECO:0000250|UniProtKB:Q9C000,
CC ECO:0000269|PubMed:20502689, ECO:0000269|PubMed:31383852,
CC ECO:0000269|PubMed:33731929}.
CC -!- FUNCTION: [NACHT, LRR and PYD domains-containing protein 1a allele 1]:
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. 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 Nlrp1a inflammasome.
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
CC (PubMed:33731929). 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. In response to pathogen-associated signals,
CC the N-terminal part of Nlrp1a is degraded by the proteasome, releasing
CC this form, which polymerizes to form the Nlrp1a inflammasome complex:
CC the Nlrp1a 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:Q9C000, ECO:0000269|PubMed:33731929}.
CC -!- ACTIVITY REGULATION: Activated by cleavage by B.anthracis lethal toxin
CC (LT) endopeptidase (PubMed:20502689). Cleavage by LT promotes
CC ubiquitination and degradation of the N-terminal part, releasing the
CC cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-
CC containing protein 1a, C-terminus), which polymerizes and forms the
CC Nlrp1a inflammasome (By similarity). Nlrp1a inflammasome is inhibited
CC by DPP8 and DPP9, which sequester the C-terminal fragment of Nlrp1a
CC (NACHT, LRR and PYD domains-containing protein 1a, C-terminus) in a
CC ternary complex, thereby preventing Nlrp1a oligomerization and
CC activation (PubMed:33731929). Nlrp1a inflammasome is weakly activated
CC by Val-boroPro (Talabostat, PT-100), an inhibitor of dipeptidyl
CC peptidases DPP8 and DPP9 (PubMed:31383852). Val-boroPro relieves
CC inhibition of DPP8 and/or DPP9 by promoting disruption of the ternary
CC complex, releasing its C-terminal part from autoinhibition (By
CC similarity). Weakly activated by Toxoplasma gondii (PubMed:31383852).
CC {ECO:0000250|UniProtKB:Q2LKW6, ECO:0000250|UniProtKB:Q9C000,
CC ECO:0000269|PubMed:20502689, ECO:0000269|PubMed:31383852,
CC ECO:0000269|PubMed:33731929}.
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 (PubMed:33731929). DPP9 acts via formation of a ternary
CC complex, composed of a DPP9 homodimer, one full-length NLRP1 protein,
CC and one cleaved C-terminus of Nlrp1a (NACHT, LRR and PYD domains-
CC containing protein 1a, C-terminus) (PubMed:33731929). 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, ECO:0000269|PubMed:33731929}.
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). The Nlrp1a inflammasome polymeric
CC complex directly recruits pro-caspase-1 (proCASP1) independently of
CC PYCARD/ASC (By similarity). Interacts (via CARD domain) with CASP1 (via
CC 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 -!- SUBCELLULAR LOCATION: [NACHT, LRR and PYD domains-containing protein
CC 1a, C-terminus]: Inflammasome {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. 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 allele 1]:
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:0000250|UniProtKB:Q9C000}.
CC -!- PTM: [NACHT, LRR and PYD domains-containing protein 1a, 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 1a, C-terminus), which polymerizes
CC and forms the Nlrp1a inflammasome. {ECO:0000305|PubMed:20502689}.
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 -!- POLYMORPHISM: Nlrp1a gene is extremely polymorphic. 5 alleles have been
CC described: 1 (this entry), 2 (AC D9I2G3), 3 (AC D9I2H0), 4 (AC D9I2G1)
CC and 5 (AC D9I2G4). {ECO:0000269|PubMed:20502689}.
CC -!- SIMILARITY: Belongs to the NLRP family. {ECO:0000305}.
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DR EMBL; AABR07029887; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07029888; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07029889; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC095695; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; HM060628; ADI96225.1; -; mRNA.
DR EMBL; HM060629; ADI96226.1; -; mRNA.
DR EMBL; HM060631; ADI96228.1; -; mRNA.
DR EMBL; HM060634; ADI96231.1; -; mRNA.
DR EMBL; HM060637; ADI96234.1; -; mRNA.
DR RefSeq; NP_001139227.2; NM_001145755.2.
DR RefSeq; XP_006246817.1; XM_006246755.3.
DR PDB; 7CRV; X-ray; 2.00 A; A/C=783-968, B/D=969-1122.
DR PDB; 7CRW; EM; 3.18 A; A/B=1-1218.
DR PDBsum; 7CRV; -.
DR PDBsum; 7CRW; -.
DR AlphaFoldDB; D9I2F9; -.
DR SMR; D9I2F9; -.
DR STRING; 10116.ENSRNOP00000034130; -.
DR PhosphoSitePlus; D9I2F9; -.
DR PaxDb; D9I2F9; -.
DR PeptideAtlas; D9I2F9; -.
DR GeneID; 360557; -.
DR KEGG; rno:360557; -.
DR UCSC; RGD:1310963; rat.
DR CTD; 195046; -.
DR RGD; 1310963; Nlrp1a.
DR VEuPathDB; HostDB:ENSRNOG00000023143; -.
DR eggNOG; ENOG502S4A4; Eukaryota.
DR InParanoid; D9I2F9; -.
DR OrthoDB; 114368at2759; -.
DR TreeFam; TF340267; -.
DR Reactome; R-RNO-844455; The NLRP1 inflammasome.
DR Proteomes; UP000002494; Chromosome 10.
DR ExpressionAtlas; D9I2F9; baseline and differential.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0072558; C:NLRP1 inflammasome complex; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; ISO:RGD.
DR GO; GO:0016887; F:ATP hydrolysis activity; ISO:RGD.
DR GO; GO:0140608; F:cysteine-type endopeptidase activator activity; ISS:UniProtKB.
DR GO; GO:0003690; F:double-stranded DNA binding; ISO:RGD.
DR GO; GO:0003725; F:double-stranded RNA binding; ISO:RGD.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0008233; F:peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0019904; F:protein domain specific binding; ISO:RGD.
DR GO; GO:0043621; F:protein self-association; ISS:UniProtKB.
DR GO; GO:0097110; F:scaffold protein binding; IPI:RGD.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
DR GO; GO:0140374; P:antiviral innate immune response; ISO:RGD.
DR GO; GO:0042742; P:defense response to bacterium; ISO:RGD.
DR GO; GO:0051607; P:defense response to virus; ISO:RGD.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0051245; P:negative regulation of cellular defense response; IMP:RGD.
DR GO; GO:0051402; P:neuron apoptotic process; ISO:RGD.
DR GO; GO:1904784; P:NLRP1 inflammasome complex assembly; ISO:RGD.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISO:RGD.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISO:RGD.
DR GO; GO:0140639; P:positive regulation of pyroptosis; IMP:RGD.
DR GO; GO:0097300; P:programmed necrotic cell death; ISO:RGD.
DR GO; GO:0051260; P:protein homooligomerization; ISS:UniProtKB.
DR GO; GO:0070269; P:pyroptosis; ISO:RGD.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro.
DR GO; GO:0032495; P:response to muramyl dipeptide; ISO:RGD.
DR GO; GO:0097264; P:self proteolysis; ISO:RGD.
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; 2.
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 3D-structure; ATP-binding; Cytoplasm; Hydrolase; Immunity; Inflammasome;
KW Inflammatory response; Innate immunity; Leucine-rich repeat; Necrosis;
KW Nucleotide-binding; Nucleus; Protease; Reference proteome; Repeat;
KW Ubl conjugation.
FT CHAIN 1..1218
FT /note="NACHT, LRR and PYD domains-containing protein 1a
FT allele 1"
FT /id="PRO_0000452878"
FT CHAIN 1..968
FT /note="NACHT, LRR and PYD domains-containing protein 1a, N-
FT terminus"
FT /evidence="ECO:0000250|UniProtKB:Q9C000"
FT /id="PRO_0000452879"
FT CHAIN 969..1218
FT /note="NACHT, LRR and PYD domains-containing protein 1a, C-
FT terminus"
FT /evidence="ECO:0000250|UniProtKB:Q9C000"
FT /id="PRO_0000452880"
FT DOMAIN 175..484
FT /note="NACHT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT REPEAT 343..364
FT /note="LRR 1"
FT /evidence="ECO:0000255"
FT REPEAT 673..693
FT /note="LRR 2"
FT /evidence="ECO:0000255"
FT REPEAT 730..750
FT /note="LRR 3"
FT /evidence="ECO:0000255"
FT DOMAIN 835..1118
FT /note="FIIND"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01174"
FT DOMAIN 1122..1211
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT REGION 1..61
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 799..842
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 835..968
FT /note="ZU5"
FT /evidence="ECO:0000250|UniProtKB:Q9C000"
FT REGION 969..1118
FT /note="UPA"
FT /evidence="ECO:0000250|UniProtKB:Q9C000"
FT COMPBIAS 8..27
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 28..43
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 799..825
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 181..188
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT SITE 942
FT /note="Trigger for autolytic processing"
FT /evidence="ECO:0000269|PubMed:33731929"
FT SITE 968..969
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01174,
FT ECO:0000269|PubMed:33731929"
FT MUTAGEN 942
FT /note="H->E: Complete loss of autocatalytic processing."
FT /evidence="ECO:0000269|PubMed:33731929"
FT MUTAGEN 969
FT /note="S->A: Abolished autolytic processing."
FT /evidence="ECO:0000269|PubMed:33731929"
FT HELIX 831..833
FT /evidence="ECO:0007829|PDB:7CRV"
FT STRAND 835..837
FT /evidence="ECO:0007829|PDB:7CRV"
FT STRAND 840..842
FT /evidence="ECO:0007829|PDB:7CRV"
FT STRAND 845..848
FT /evidence="ECO:0007829|PDB:7CRV"
FT TURN 849..852
FT /evidence="ECO:0007829|PDB:7CRV"
FT STRAND 853..858
FT /evidence="ECO:0007829|PDB:7CRV"
FT STRAND 860..865
FT /evidence="ECO:0007829|PDB:7CRV"
FT TURN 867..869
FT /evidence="ECO:0007829|PDB:7CRV"
FT STRAND 872..877
FT /evidence="ECO:0007829|PDB:7CRV"
FT STRAND 879..886
FT /evidence="ECO:0007829|PDB:7CRV"
FT HELIX 888..890
FT /evidence="ECO:0007829|PDB:7CRV"
FT HELIX 898..900
FT /evidence="ECO:0007829|PDB:7CRV"
FT STRAND 901..903
FT /evidence="ECO:0007829|PDB:7CRV"
FT STRAND 907..911
FT /evidence="ECO:0007829|PDB:7CRV"
FT STRAND 916..923
FT /evidence="ECO:0007829|PDB:7CRV"
FT HELIX 935..937
FT /evidence="ECO:0007829|PDB:7CRV"
FT STRAND 938..944
FT /evidence="ECO:0007829|PDB:7CRV"
FT STRAND 947..951
FT /evidence="ECO:0007829|PDB:7CRV"
FT STRAND 954..956
FT /evidence="ECO:0007829|PDB:7CRV"
FT STRAND 958..965
FT /evidence="ECO:0007829|PDB:7CRV"
FT STRAND 970..976
FT /evidence="ECO:0007829|PDB:7CRV"
FT TURN 979..983
FT /evidence="ECO:0007829|PDB:7CRV"
FT STRAND 989..998
FT /evidence="ECO:0007829|PDB:7CRV"
FT STRAND 1001..1011
FT /evidence="ECO:0007829|PDB:7CRV"
FT HELIX 1013..1024
FT /evidence="ECO:0007829|PDB:7CRV"
FT TURN 1025..1027
FT /evidence="ECO:0007829|PDB:7CRV"
FT STRAND 1029..1031
FT /evidence="ECO:0007829|PDB:7CRV"
FT STRAND 1045..1049
FT /evidence="ECO:0007829|PDB:7CRV"
FT STRAND 1054..1057
FT /evidence="ECO:0007829|PDB:7CRV"
FT STRAND 1059..1062
FT /evidence="ECO:0007829|PDB:7CRV"
FT STRAND 1075..1080
FT /evidence="ECO:0007829|PDB:7CRV"
FT STRAND 1086..1092
FT /evidence="ECO:0007829|PDB:7CRV"
FT TURN 1093..1095
FT /evidence="ECO:0007829|PDB:7CRV"
FT STRAND 1098..1104
FT /evidence="ECO:0007829|PDB:7CRV"
FT HELIX 1106..1108
FT /evidence="ECO:0007829|PDB:7CRV"
SQ SEQUENCE 1218 AA; 138392 MW; A2C22118B6194DF9 CRC64;
MEESQSKQES NTRVAQHGSQ QDVDPTFQTK RALEKERSKP RPRPLPRVQL QSLPGWSSTS
NDVPLSQLIR EMDHESRRCI HRSKKKLDRS EHISQGTIPE IYEKRKETIS HTQSMEQKYL
FQNFTKLLLL QKCCPGGSEK LVRESWHPCV PEEGGHMIEI QDLFDPNLDT EKKPQLVIIE
GAAGIGKSTL ARQVKRAWDE GQLYRDRFQH VFFFSCRELA QCKQLSLAEL IAQGQEVPTA
PTRQILSRPE KLLFILDGID EPAWVLEDQN PELCVHWSQA QPVHTLLGSL LGKSILPEAS
LMLTARTTAL QKLVPSLGQP HRVEVLGFSE FERKDYFYKY FAKERNTIID FNLIGSIPVL
LTLCEVPWVC WLLCTCLEKQ MQQGEVLSLT SQTTTALCLK YLSLTIPGQH LSTQLRTLCS
LAAEGICQRR TLFSKSDLCK QGLAEDAIAT FLKIGVLQRQ PSSLSYSFAH LCLQEFFAAM
SYILEDSEEA HGDMGNDRTV ETLVERYGRQ NLFEAPTVRF LLGLLNTREM REMENIFACK
FPWETKLKLL QSIIGEPFCQ PCHLGLFHCL YENQEEELLT ETMLCFPLTA SGPNHMEATV
FQTNVKRLVI QTDMELMVVT FCITFSHVRS LRLKGKGQQE YKLTAPAMVL YRWTPISEAS
WKVLFSNLKC TRNLEELDLS GNPLSYSAVR SLCTALRQPG CRLKTLWLVD CGLTSRCCSF
LASMLSAHSR LAELDLRLND LGDNGVRQLC EGLRNPACNL SILRLDQASL SEQVITELRA
LETKNPKLFI SSTWMSHMTM PTENTDGEES LTSSKQQQQQ SGDKHMEPLG TDDDFWGPSG
PVSTEVVDRE RNLYRVRLPM AGSYHCPSTG LHFVVTRAVT IEIGFCAWSQ FLHETPLQHS
HMVAGPLFDI KAEHGAVTAV CLPHFVSLQE GKVDSSLFHV AHFQDHGMVL ETPARVEPHF
AVLENPSFSP MGVLLRMIPA VGHFIPITSI TLIYYRLYLE DITFHLYLVP NDCTIRKAID
EEELKFQFVR INKPPPVDAL YVGSRYIVSS SKEVEILPKE LELCYRSPRE SQLFSEIYVG
NIGSGINLQL TDKKYMNLIW EALLKPGDLR PALPRMASAP KDAPALLHFV DQHREQLVAR
VTSVDPLLDK LHGLVLSEED YETVRAEATN QDKMRKLFRG SRSWSWDCKD HFYQALKETH
PHLIMDLLEK SGGVSVRL
