NLR9B_MOUSE
ID NLR9B_MOUSE Reviewed; 1003 AA.
AC Q66X22; Q6UTW9;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=NACHT, LRR and PYD domains-containing protein 9B;
DE AltName: Full=NALP-delta;
GN Name=Nlrp9b; Synonyms=Nalp9, Nalp9b;
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), TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=15317747; DOI=10.1093/hmg/ddh241;
RA Hamatani T., Falco G., Carter M.G., Akutsu H., Stagg C.A., Sharov A.A.,
RA Dudekula D.B., VanBuren V., Ko M.S.H.;
RT "Age-associated alteration of gene expression patterns in mouse oocytes.";
RL Hum. Mol. Genet. 13:2263-2278(2004).
RN [2]
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 (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=26411641; DOI=10.1262/jrd.2015-050;
RA Peng H., Lin X., Liu F., Wang C., Zhang W.;
RT "NLRP9B protein is dispensable for oocyte maturation and early embryonic
RT development in the mouse.";
RL J. Reprod. Dev. 61:559-564(2015).
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND SUBCELLULAR
RP LOCATION.
RX PubMed=28636595; DOI=10.1038/nature22967;
RA Zhu S., Ding S., Wang P., Wei Z., Pan W., Palm N.W., Yang Y., Yu H.,
RA Li H.B., Wang G., Lei X., de Zoete M.R., Zhao J., Zheng Y., Chen H.,
RA Zhao Y., Jurado K.A., Feng N., Shan L., Kluger Y., Lu J., Abraham C.,
RA Fikrig E., Greenberg H.B., Flavell R.A.;
RT "Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial
RT cells.";
RL Nature 546:667-670(2017).
CC -!- FUNCTION: As the sensor component of the NLRP9 inflammasome, plays a
CC crucial role in innate immunity and inflammation. In response to
CC pathogens, including rotavirus, initiates the formation of the
CC inflammasome polymeric complex, made of NLRP9, PYCARD and CASP1.
CC Recruitment of proCASP1 to the inflammasome promotes its activation and
CC CASP1-catalyzed IL1B and IL18 maturation and release in the
CC extracellular milieu. The active cytokines stimulate inflammatory
CC responses. Inflammasomes can also induce pyroptosis, an inflammatory
CC form of programmed cell death. NLRP9 inflammasome activation may be
CC initiated by DHX9 interaction with viral double-stranded RNA (dsRNA),
CC preferentially to short dsRNA segments. {ECO:0000269|PubMed:28636595}.
CC -!- SUBUNIT: Sensor component of NLRP9 inflammasomes. Inflammasomes are
CC supramolecular complexes that assemble in the cytosol in response to
CC pathogens, such as rotavirus, but not encephalomyocarditis virus
CC (EMCV), and play critical roles in innate immunity and inflammation.
CC The core of NLRP9 inflammasomes consists of a signal sensor component
CC (NLRP9), an adapter (ASC/PYCARD), which recruits an effector pro-
CC inflammatory caspase (CASP1). Within the complex, NLRP9 and PYCARD
CC interact via their respective DAPIN/pyrin domains. This interaction
CC initiates speck formation (nucleation) which greatly enhances further
CC addition of soluble PYCARD molecules to the speck in a prion-like
CC polymerization process. Clustered PYCARD nucleates the formation of
CC CASP1 filaments through the interaction of their respective CARD
CC domains, acting as a platform for CASP1 polymerization. CASP1 filament
CC formation increases local enzyme concentration, resulting in trans-
CC autocleavage and activation. Active CASP1 then processes IL1B and IL18
CC precursors, leading to the release of mature cytokines in the
CC extracellular milieu and inflammatory response. Interacts with DHX9
CC upon rotavirus infection; this interaction may trigger inflammasome
CC activation and inflammatory response. {ECO:0000250|UniProtKB:Q7RTR0}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:26411641}.
CC Inflammasome {ECO:0000250|UniProtKB:Q7RTR0}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q66X22-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q66X22-2; Sequence=VSP_025024, VSP_025025, VSP_025026;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in the intestine, including
CC proximal and distal colon, cecum, ileum, jejunum and duodenum (at
CC protein level) (PubMed:26411641, PubMed:28636595). In the ileum,
CC expressed in epithelial cells (PubMed:28636595). Also expressed in
CC oocytes at all follicular stages and in preimplantation embryos (at
CC protein level) (PubMed:15317747, PubMed:26411641). Although expression
CC decreases in preimplantation embryos, it is still detectable in
CC blastocyts (PubMed:26411641). {ECO:0000269|PubMed:15317747,
CC ECO:0000269|PubMed:26411641, ECO:0000269|PubMed:28636595}.
CC -!- DEVELOPMENTAL STAGE: Down-regulated in preimplantation embryos, with
CC decreased levels observed at the 4-cell stages. Still detectable in
CC blastocysts (at protein level) (PubMed:15317747). Expression in oocytes
CC decline with age. It is much higher at 10 weeks of age rather than at
CC 40 (at protein level) (PubMed:26411641). In ileum epithelial cells, up-
CC regulated in the first 12 hours following rotavirus infection. Levels
CC drastically decrease 36 hours post infection (at protein level)
CC (PubMed:28636595). {ECO:0000269|PubMed:15317747,
CC ECO:0000269|PubMed:26411641, ECO:0000269|PubMed:28636595}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Mutant mice exhibit normal
CC gut homeostasis and microbiota composition. Following rotavirus
CC infection, mutant animals have higher viral loads in the small
CC intestine, increased fecal shedding of viral antigens, and more
CC frequent incidences of diarrhea compared to wild-type littermates. Mice
CC with a conditional knockout in ileum intestinal epithelial cells are
CC also more susceptible to rotavirus infection compared to control
CC animals. {ECO:0000269|PubMed:28636595}.
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DR EMBL; AY596196; AAU06317.1; -; mRNA.
DR EMBL; AY360471; AAQ64009.1; -; mRNA.
DR CCDS; CCDS20920.1; -. [Q66X22-1]
DR RefSeq; NP_918947.2; NM_194058.2. [Q66X22-1]
DR RefSeq; XP_006540001.1; XM_006539938.2. [Q66X22-1]
DR RefSeq; XP_006540002.1; XM_006539939.2. [Q66X22-1]
DR AlphaFoldDB; Q66X22; -.
DR SMR; Q66X22; -.
DR STRING; 10090.ENSMUSP00000072895; -.
DR iPTMnet; Q66X22; -.
DR PhosphoSitePlus; Q66X22; -.
DR PaxDb; Q66X22; -.
DR PRIDE; Q66X22; -.
DR ProteomicsDB; 293577; -. [Q66X22-1]
DR DNASU; 243874; -.
DR Ensembl; ENSMUST00000073151; ENSMUSP00000072895; ENSMUSG00000060508. [Q66X22-1]
DR Ensembl; ENSMUST00000117909; ENSMUSP00000113762; ENSMUSG00000060508. [Q66X22-2]
DR GeneID; 243874; -.
DR KEGG; mmu:243874; -.
DR UCSC; uc009fnt.1; mouse. [Q66X22-1]
DR UCSC; uc012fbm.1; mouse. [Q66X22-2]
DR CTD; 243874; -.
DR MGI; MGI:2675377; Nlrp9b.
DR VEuPathDB; HostDB:ENSMUSG00000060508; -.
DR eggNOG; KOG4308; Eukaryota.
DR GeneTree; ENSGT00940000163218; -.
DR HOGENOM; CLU_002274_2_1_1; -.
DR InParanoid; Q66X22; -.
DR OMA; PWIDEEY; -.
DR OrthoDB; 114368at2759; -.
DR PhylomeDB; Q66X22; -.
DR BioGRID-ORCS; 243874; 1 hit in 71 CRISPR screens.
DR PRO; PR:Q66X22; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q66X22; protein.
DR Bgee; ENSMUSG00000060508; Expressed in animal zygote and 31 other tissues.
DR ExpressionAtlas; Q66X22; baseline and differential.
DR Genevisible; Q66X22; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0061702; C:inflammasome complex; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0001824; P:blastocyst development; IGI:MGI.
DR GO; GO:0051607; P:defense response to virus; IMP:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IMP:UniProtKB.
DR GO; GO:0032741; P:positive regulation of interleukin-18 production; IMP:UniProtKB.
DR GO; GO:0070269; P:pyroptosis; IMP:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; IBA:GO_Central.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR004020; DAPIN.
DR InterPro; IPR011029; DEATH-like_dom_sf.
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; PF05729; NACHT; 1.
DR Pfam; PF17776; NLRC4_HD2; 1.
DR Pfam; PF17779; NOD2_WH; 1.
DR Pfam; PF02758; PYRIN; 1.
DR SMART; SM01289; PYRIN; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50824; DAPIN; 1.
DR PROSITE; PS50837; NACHT; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cytoplasm; Immunity; Inflammasome;
KW Inflammatory response; Innate immunity; Leucine-rich repeat;
KW Nucleotide-binding; Reference proteome; Repeat.
FT CHAIN 1..1003
FT /note="NACHT, LRR and PYD domains-containing protein 9B"
FT /id="PRO_0000286336"
FT DOMAIN 1..91
FT /note="Pyrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00061"
FT DOMAIN 143..465
FT /note="NACHT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT REPEAT 749..770
FT /note="LRR 1"
FT REPEAT 778..799
FT /note="LRR 2"
FT REPEAT 806..826
FT /note="LRR 3"
FT REPEAT 835..856
FT /note="LRR 4"
FT REPEAT 863..883
FT /note="LRR 5"
FT REPEAT 892..913
FT /note="LRR 6"
FT REPEAT 920..940
FT /note="LRR 7"
FT BINDING 149..156
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT VAR_SEQ 178..617
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_025024"
FT VAR_SEQ 842..898
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_025025"
FT VAR_SEQ 955..1003
FT /note="LDKSAFSEESQTLLQDVEKKNNNLNILHHPWFEAERNKRGTRLVWNSRN ->
FT SGELMFLMKWKDSDEADLVQAKEANMICPQIVISFYGERLTWHS (in isoform
FT 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_025026"
SQ SEQUENCE 1003 AA; 114802 MW; CDC853C75A26EC91 CRC64;
MAGSSGYGLL KLLQKLSDEE FQRFKELLRE EPEKFKLKPI SWTKIENSSK ESLVTLLNTH
YPGQAWNMML SLFLQVNRED LSIMAQKKKR HKQTKYKKFM KTTFERIWTL ETNTHIPDRN
YHLIVEVQYK ALQEIFDSES EPVTAIVAGT TGEGKTTFLR KAMLDWASGV LLQNRFQYVF
FFSVFSLNNT TELSLAELIS STLPESSETV DDILSDPKRI LFILDGFDYL KFDLELRTNL
CNDWRKRLPT QIVLSSLLQK IMLPGCSLLL ELGQISVPKI RHLLKYPRVI TMQGFSERSV
EFYCMSFFDN QRGIEVAENL RNNEVLHLCS NPYLCWMFCS CLKWQFDREE EGYFKAKTDA
AFFTNFMVSA FKSTYAHSPS KQNRARLKTL CTLAVEGMWK ELFVFDSEDL RRNGISESDK
AVWLKMQFLQ THGNHTVFYH PTLQSYFAAM FYFLKQDKDI CVPVIGSIPQ LLGNMYARGQ
TQWLQLGTFL FGLINEQVAA LLQPCFGFIQ PIYVRQEIIC YFKCLGQQEC NEKLERSQTL
FSCLRDSQEE RFVRQVVDLL EEITVDISSS DVLSVTAYAL QKSSKLKKLH LHIQKTVFSE
IYCPDHCKTR TSIGKRRNTA EYWKTLCGIF CNLYVLDLDS CQFNKRAIQD LCNSMSPTPT
VPLTAFKLQS LSCSFMADFG DGSLFHTLLQ LPHLKYLNLY GTYLSMDVTE KLCAALRCSA
CRVEELLLGK CGISSKACGI IAISLINSKV KHLSLVENPL KNKGVMSLCE MLKDPSCVLQ
SLMLSYCCLT FIACGHLYEA LLSNKHLSLL DLGSNFLEDT GVNLLCEALK DPNCTLKELW
LPGCFLTSQC CEEISAVLIC NRNLKTLKLG NNNIQDTGVR QLCEALSHPN CNLECLGLDL
CEFTSDCCKD LALALTTCKT LNSLNLDWKT LDHSGLVVLC EALNHKRCNL KMLGLDKSAF
SEESQTLLQD VEKKNNNLNI LHHPWFEAER NKRGTRLVWN SRN
