NLRP1_DANRE
ID NLRP1_DANRE Reviewed; 1355 AA.
AC A0A386CAB9; K7DYI4;
DT 11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT 05-DEC-2018, sequence version 1.
DT 03-AUG-2022, entry version 19.
DE RecName: Full=NACHT, LRR and PYD domains-containing protein 1 homolog {ECO:0000305};
DE EC=3.4.-.- {ECO:0000250|UniProtKB:Q9C000};
DE Contains:
DE RecName: Full=NACHT, LRR and PYD domains-containing protein 1, C-terminus {ECO:0000305};
DE Short=NLRP1-CT {ECO:0000250|UniProtKB:Q9C000};
DE Contains:
DE RecName: Full=NACHT, LRR and PYD domains-containing protein 1, N-terminus {ECO:0000305};
DE Short=NLRP1-NT {ECO:0000250|UniProtKB:Q9C000};
GN Name=nlrp1 {ECO:0000303|PubMed:30150286}; ORFNames=si:ch211-66k16.28;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955 {ECO:0000312|EMBL:AYC80945.1};
RN [1] {ECO:0000312|EMBL:AYC80945.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, IDENTIFICATION IN
RP INFLAMMASOME, INTERACTION WITH PYCARD, TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, INDUCTION BY E.TARDA, DOMAIN, AND DISRUPTION PHENOTYPE.
RX PubMed=30150286; DOI=10.4049/jimmunol.1800498;
RA Li J.Y., Gao K., Shao T., Fan D.D., Hu C.B., Sun C.C., Dong W.R., Lin A.F.,
RA Xiang L.X., Shao J.Z.;
RT "Characterization of an NLRP1 Inflammasome from Zebrafish Reveals a Unique
RT Sequential Activation Mechanism Underlying Inflammatory Caspases in Ancient
RT Vertebrates.";
RL J. Immunol. 201:1946-1966(2018).
RN [2] {ECO:0000312|Proteomes:UP000000437}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen {ECO:0000312|Proteomes:UP000000437};
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
CC -!- FUNCTION: Acts as the sensor component of the nlrp1 inflammasome, which
CC mediates inflammasome activation in response to various pathogen-
CC associated signals, leading to subsequent pyroptosis (PubMed:30150286).
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:30150286).
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 nlrp1 is degraded
CC by the proteasome, releasing the cleaved C-terminal part of the protein
CC (NACHT, LRR and PYD domains-containing protein 1, C-terminus), which
CC polymerizes to initiate the formation of the inflammasome complex: the
CC inflammasome recruits and activate pro-inflammatory caspases (caspa
CC and/or caspb), leading to pyroptosis (By similarity).
CC {ECO:0000250|UniProtKB:Q9C000, ECO:0000269|PubMed:30150286}.
CC -!- FUNCTION: [NACHT, LRR and PYD domains-containing protein 1 homolog]:
CC Constitutes the precursor of the nlrp1 inflammasome, which mediates
CC autoproteolytic processing within the FIIND domain to generate the N-
CC terminal and C-terminal parts, which are associated non-covalently in
CC absence of pathogens and other damage-associated signals.
CC {ECO:0000250|UniProtKB:Q9C000}.
CC -!- FUNCTION: [NACHT, LRR and PYD domains-containing protein 1, N-
CC terminus]: Regulatory part that prevents formation of the nlrp1
CC inflammasome: in absence of pathogens and other damage-associated
CC signals, interacts with the C-terminal part of nlrp1 (NACHT, LRR and
CC PYD domains-containing protein 1, C-terminus), preventing activation of
CC the nlrp1 inflammasome (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 nlrp1 inflammasome (By similarity).
CC {ECO:0000250|UniProtKB:Q9C000}.
CC -!- FUNCTION: [NACHT, LRR and PYD domains-containing protein 1, C-
CC terminus]: Constitutes the active part of the nlrp1 inflammasome (By
CC similarity). In absence of pathogens and other damage-associated
CC signals, interacts with the N-terminal part of nlrp1 (NACHT, LRR and
CC PYD domains-containing protein 1, N-terminus), preventing activation of
CC the nlrp1 inflammasome (By similarity). In response to pathogen-
CC associated signals, the N-terminal part of nlrp1 is degraded by the
CC proteasome, releasing this form, which polymerizes to form the nlrp1
CC inflammasome complex: the nlrp1 inflammasome complex then directly
CC recruits and activates pro-inflammatory caspases (caspa and/or caspb)
CC activation, leading to subsequent pyroptosis (By similarity).
CC {ECO:0000250|UniProtKB:Q9C000}.
CC -!- ACTIVITY REGULATION: nlrp1 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 1,
CC C-terminus), which polymerizes and forms the nlrp1 inflammasome.
CC {ECO:0000250|UniProtKB:Q9C000}.
CC -!- SUBUNIT: [NACHT, LRR and PYD domains-containing protein 1, N-terminus]:
CC Interacts with the C-terminal part of nlrp1 (NACHT, LRR and PYD
CC domains-containing protein 1, C-terminus) in absence of pathogens and
CC other damage-associated signals. {ECO:0000250|UniProtKB:Q9C000}.
CC -!- SUBUNIT: [NACHT, LRR and PYD domains-containing protein 1, C-terminus]:
CC Interacts with the N-terminal part of nlrp1 (NACHT, LRR and PYD
CC domains-containing protein 1, N-terminus) in absence of pathogens and
CC other damage-associated signals (By similarity). Homomultimer; forms
CC the nlrp1 inflammasome polymeric complex, a filament composed of
CC homopolymers of this form in response to pathogens and other damage-
CC associated signals (By similarity). The nlrp1 inflammasome polymeric
CC complex associates with pycard/asc (PubMed:30150286). Interacts (via
CC CARD domain) with pycard/asc (via CARD domain); leading to pro-
CC inflammatory caspases (caspa and/or caspb) recruitment
CC (PubMed:30150286). Pro-caspase-a and pro-caspase-b filament formation
CC increases local enzyme concentration, resulting in trans-autocleavage
CC and activation. Active caspa and caspb then processes il1b and il18
CC precursors, leading to the release of mature cytokines in the
CC extracellular milieu and inflammatory response (By similarity).
CC {ECO:0000250|UniProtKB:Q9C000, ECO:0000269|PubMed:30150286}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:30150286}. Note=Co-
CC localizes with pycard, caspa and caspb in the cytoplasm.
CC {ECO:0000269|PubMed:30150286}.
CC -!- SUBCELLULAR LOCATION: [NACHT, LRR and PYD domains-containing protein 1,
CC C-terminus]: Inflammasome {ECO:0000269|PubMed:30150286}.
CC -!- TISSUE SPECIFICITY: Expressed in adult spleen, head kidney, gill and
CC skin and also in the embryo. {ECO:0000269|PubMed:30150286}.
CC -!- DEVELOPMENTAL STAGE: In the embryo, highest expression at 2 hours post-
CC fertilization (hpf) with levels decreasing in later stages.
CC {ECO:0000269|PubMed:30150286}.
CC -!- INDUCTION: Up-regulated in response to infection with the bacteriim
CC E.tarda. {ECO:0000269|PubMed:30150286}.
CC -!- DOMAIN: The CARD domain is involved in the interaction with pycard.
CC {ECO:0000269|PubMed:30150286}.
CC -!- DOMAIN: [NACHT, LRR and PYD domains-containing protein 1, C-terminus]:
CC The C-terminal part of nlrp1 oligomerizes to form the core of the nlrp1
CC inflammasome filament: in the filament, the CARD domains form a central
CC helical filaments that are promoted by oligomerized, but flexibly
CC linked, UPA regions surrounding the filaments.
CC {ECO:0000250|UniProtKB:Q9C000}.
CC -!- PTM: [NACHT, LRR and PYD domains-containing protein 1 homolog]:
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 pro-
CC inflammatory caspases (caspa and/or caspb) binding. Both N- and C-
CC terminal parts remain associated non-covalently.
CC {ECO:0000250|UniProtKB:Q9C000}.
CC -!- PTM: [NACHT, LRR and PYD domains-containing protein 1, 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 1, C-terminus), which polymerizes and forms the nlrp1
CC inflammasome. {ECO:0000250|UniProtKB:Q9C000}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown in embryos 6 hours post-
CC fertilization (hpf) results in reduced caspa and caspb activation
CC following bacterial infection with E.tarda.
CC {ECO:0000269|PubMed:30150286}.
CC -!- SIMILARITY: Belongs to the NLRP family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; MH118554; AYC80945.1; -; mRNA.
DR EMBL; BX005331; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR450720; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_009297081.1; XM_009298806.2.
DR AlphaFoldDB; A0A386CAB9; -.
DR SMR; A0A386CAB9; -.
DR ComplexPortal; CPX-4947; NLRP1 inflammasome, variant 1.
DR ComplexPortal; CPX-4948; NLRP1 inflammasome, variant 2.
DR STRING; 7955.ENSDARP00000126513; -.
DR GeneID; 101882558; -.
DR KEGG; dre:101882558; -.
DR CTD; 22861; -.
DR ZFIN; ZDB-GENE-120709-59; nlrp1.
DR eggNOG; ENOG502QS9E; Eukaryota.
DR HOGENOM; CLU_002274_2_4_1; -.
DR Reactome; R-DRE-3134975; Regulation of innate immune responses to cytosolic DNA.
DR Reactome; R-DRE-3270619; IRF3-mediated induction of type I IFN.
DR PRO; PR:A0A386CAB9; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IC:ComplexPortal.
DR GO; GO:0072558; C:NLRP1 inflammasome complex; IDA:ComplexPortal.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008233; F:peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0002221; P:pattern recognition receptor signaling pathway; IC:ComplexPortal.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IC:ComplexPortal.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IC:ComplexPortal.
DR GO; GO:0012501; P:programmed cell death; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro.
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; 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; 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 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 ATP-binding; Cytoplasm; Hydrolase; Immunity; Inflammasome;
KW Inflammatory response; Innate immunity; Necrosis; Nucleotide-binding;
KW Protease; Reference proteome; Repeat; Ubl conjugation.
FT CHAIN 1..1355
FT /note="NACHT, LRR and PYD domains-containing protein 1
FT homolog"
FT /id="PRO_0000448789"
FT CHAIN 1..1109
FT /note="NACHT, LRR and PYD domains-containing protein 1, N-
FT terminus"
FT /evidence="ECO:0000250|UniProtKB:Q9C000"
FT /id="PRO_0000452861"
FT CHAIN 1110..1182
FT /note="NACHT, LRR and PYD domains-containing protein 1, C-
FT terminus"
FT /evidence="ECO:0000250|UniProtKB:Q9C000"
FT /id="PRO_0000452862"
FT DOMAIN 257..458
FT /note="NACHT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT DOMAIN 977..1252
FT /note="FIIND"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01174"
FT DOMAIN 1278..1354
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT REGION 977..1109
FT /note="ZU5"
FT /evidence="ECO:0000250|UniProtKB:Q9C000"
FT REGION 1110..1252
FT /note="UPA"
FT /evidence="ECO:0000250|UniProtKB:Q9C000"
FT BINDING 263..270
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT SITE 1109..1110
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:Q9C000,
FT ECO:0000255|PROSITE-ProRule:PRU01174"
SQ SEQUENCE 1355 AA; 154257 MW; 9C98D90D3F622A93 CRC64;
MSSDYTDRNN LASAIKTLGD MLEKDEAFQR LMYNASTKGE INRGRVNKVF LKALLSAGDK
VGEFLNELID HLNLFKVLGD FSWNPPVLKE AELNERTSQL RTQQHKYVER VSGFSHYGFG
ETGTPARGDI TSPRGPQVAS IEEDLATSKL AELLLAVGDH LEKIEKKGQF LPENVERFSL
DCFITSESVK LSSEAVELAP CYTEPVIIQR SKEQTEKYCQ EYVRSPHTSS HLLSNDKTQS
IRIGQLFSPD SDGNTPKTVI LCGDSGRGKS FVLEKIILDW VHLEHHFENF DAVFLLKYEE
LKCLSEEMSL TELLSRSCSL TSDQISQILQ LTPEKVLFLI DGIDDFSFNA HIQISSPTDP
SQKAPVISII HCLMRDLLLV ESSVIVTTRY TAAAELSSLC KRPQRFTEIE GFSERRVQEY
FQKFFQDEQL FKKAYESMKT NETLLTFCSV PLLCWMVCFC LKKDADQVMT ELKTTTSIYV
HFVSTLLEDH HQSQSFLRSL GQLAEEGMKN RQNLFDEKSV TRTGLDPATR VFMNKIYLKR
KKKHELLFKF KHLSFQEFFA ALYYIMLDEE ESWCKVSELF NMMESEALIH RSPPIFRGRL
SNPIPSVMMF LCGLFNKKVS SSLFEKMKST FSHNVKLKKK ELKKKLMKMI PAMIRQYGFE
LFALHCLYEL QDERFVTKVL ETHKFIDLSN VSLRSTDCLV LCYCLRLCPN IRELNFMNCD
LTAAKLKILQ PALGLCETLR FSVEHLSEIG DLIQILSESK ILRELKVRED EYGVESPRWS
FNLSVTRGDV LLTLSSSEKN PSFSSVLNIR LTCAQSQISR TDWTLFLQRL RKTGTLTEDS
SADDDHVSLQ LSSLHSVGLK SLDLTLVSLN ESWASGIISL IQNCTSLQQL KVSVTGLLLE
EGLKLLKKSL TDPHCTVIIE GRRNCSEPSE EHLRQSYEKV EIHFKPKLLE ELAELSICNP
GSSALNIHCQ SCVDVADSDQ WVQVEPSVCR GEGGTEFRIT TPAGRFQCSR TRMRWVCDGD
VTLHYRAVDG HFLNAELERL QCERVAPVLD VNVISGKLEE AHLPHYMCLA ESDPALTNAV
KLLSVEDEGI SLESVELTRF HAKILQPMFS PKTVLVKLGI PVKVHCDLLI FMTHTCPIIL
NVYFFPSDSL VEENIKTEEK SSHQIKCSRP EAPLQMKKQH SLEVPDAVVQ PEAIKLRGNM
KPNFFQVKQP VVNDITMILS RVDDQKSVWT GTIWKKLIDI KLNKTESDLF QSGQKHKTSQ
PAHSFDKAQF FDTHWCNLIK SVENVDTVAD KLLQKQIIHE QFYSEIIHHK STSEESMRKI
CVIVRKGSAA VKEIFISILL QENPNLLNHL PSSDS
