Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

NACHT, LRR and PYD domains-containing protein 9B

Gene

Nlrp9b

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

As the sensor component of the NLRP9 inflammasome, plays a crucial role in innate immunity and inflammation. In response to pathogens, including rotavirus, initiates the formation of the inflammasome polymeric complex, made of NLRP9, PYCARD and CASP1. Recruitment of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and release in the extracellular milieu. The active cytokines stimulate inflammatory responses. Inflammasomes can also induce pyroptosis, an inflammatory form of programmed cell death. NLRP9 inflammasome activation may be initiated by DHX9 interaction with viral double-stranded RNA (dsRNA), preferentially to short dsRNA segments.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi149 – 156ATPPROSITE-ProRule annotation8

GO - Molecular functioni

Keywordsi

Biological processImmunity, Inflammatory response, Innate immunity
LigandATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
NACHT, LRR and PYD domains-containing protein 9B
Alternative name(s):
NALP-delta
Gene namesi
Name:Nlrp9b
Synonyms:Nalp9, Nalp9b
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:2675377. Nlrp9b.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Inflammasome

Pathology & Biotechi

Disruption phenotypei

No visible phenotype. Mutant mice exhibit normal gut homeostasis and microbiota composition. Following rotavirus infection, mutant animals have higher viral loads in the small intestine, increased fecal shedding of viral antigens, and more frequent incidences of diarrhea compared to wild-type littermates. Mice with a conditional knockout in ileum intestinal epithelial cells are also more susceptible to rotavirus infection compared to control animals.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002863361 – 1003NACHT, LRR and PYD domains-containing protein 9BAdd BLAST1003

Proteomic databases

PaxDbiQ66X22.
PRIDEiQ66X22.

PTM databases

iPTMnetiQ66X22.
PhosphoSitePlusiQ66X22.

Expressioni

Tissue specificityi

Predominantly expressed in the intestine, including proximal and distal colon, cecum, ileum, jejunum and duodenum (at protein level) (PubMed:26411641, PubMed:28636595). In the ileum, expressed in epithelial cells (PubMed:28636595). Also expressed in oocytes at all follicular stages and in preimplantation embryos (at protein level) (PubMed:15317747, PubMed:26411641). Although expression decreases in preimplantation embryos, it is still detectable in blastocyts (PubMed:26411641).3 Publications

Developmental stagei

Down-regulated in preimplantation embryos, with decreased levels observed at the 4-cell stages. Still detectable in blastocysts (at protein level) (PubMed:15317747). Expression in oocytes decline with age. It is much higher at 10 weeks of age rather than at 40 (at protein level) (PubMed:26411641). In ileum epithelial cells, up-regulated in the first 12 hours following rotavirus infection. Levels drastically decrease 36 hours post infection (at protein level) (PubMed:28636595).3 Publications

Gene expression databases

BgeeiENSMUSG00000060508.
CleanExiMM_NLRP9B.
ExpressionAtlasiQ66X22. baseline and differential.
GenevisibleiQ66X22. MM.

Interactioni

Subunit structurei

Sensor component of NLRP9 inflammasomes. Inflammasomes are supramolecular complexes that assemble in the cytosol in response to pathogens, such as rotavirus, but not encephalomyocarditis virus (EMCV), and play critical roles in innate immunity and inflammation. The core of NLRP9 inflammasomes consists of a signal sensor component (NLRP9), an adapter (ASC/PYCARD), which recruits an effector proinflammatory caspase (CASP1). Within the complex, NLRP9 and PYCARD interact via their respective DAPIN/pyrin domains. This interaction initiates speck formation (nucleation) which greatly enhances further addition of soluble PYCARD molecules to the speck in a prion-like polymerization process. Clustered PYCARD nucleates the formation of CASP1 filaments through the interaction of their respective CARD domains, acting as a platform for CASP1 polymerization. CASP1 filament formation increases local enzyme concentration, resulting in trans-autocleavage and activation. Active CASP1 then processes IL1B and IL18 precursors, leading to the release of mature cytokines in the extracellular milieu and inflammatory response. Interacts with DHX9 upon rotavirus infection; this interaction may trigger inflammasome activation and inflammatory response.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000072895.

Structurei

3D structure databases

ProteinModelPortaliQ66X22.
SMRiQ66X22.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 91PyrinPROSITE-ProRule annotationAdd BLAST91
Domaini143 – 465NACHTPROSITE-ProRule annotationAdd BLAST323
Repeati749 – 770LRR 1Add BLAST22
Repeati778 – 799LRR 2Add BLAST22
Repeati806 – 826LRR 3Add BLAST21
Repeati835 – 856LRR 4Add BLAST22
Repeati863 – 883LRR 5Add BLAST21
Repeati892 – 913LRR 6Add BLAST22
Repeati920 – 940LRR 7Add BLAST21

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiKOG4308. Eukaryota.
ENOG410ZBX3. LUCA.
GeneTreeiENSGT00860000133669.
HOGENOMiHOG000294064.
HOVERGENiHBG063656.
InParanoidiQ66X22.
OMAiRILFIMD.
OrthoDBiEOG091G01CG.
PhylomeDBiQ66X22.

Family and domain databases

InterProiView protein in InterPro
IPR004020. DAPIN.
IPR011029. DEATH-like_dom.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
PfamiView protein in Pfam
PF02758. PYRIN. 1 hit.
SMARTiView protein in SMART
SM01289. PYRIN. 1 hit.
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEiView protein in PROSITE
PS50824. DAPIN. 1 hit.
PS50837. NACHT. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q66X22-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAGSSGYGLL KLLQKLSDEE FQRFKELLRE EPEKFKLKPI SWTKIENSSK
60 70 80 90 100
ESLVTLLNTH YPGQAWNMML SLFLQVNRED LSIMAQKKKR HKQTKYKKFM
110 120 130 140 150
KTTFERIWTL ETNTHIPDRN YHLIVEVQYK ALQEIFDSES EPVTAIVAGT
160 170 180 190 200
TGEGKTTFLR KAMLDWASGV LLQNRFQYVF FFSVFSLNNT TELSLAELIS
210 220 230 240 250
STLPESSETV DDILSDPKRI LFILDGFDYL KFDLELRTNL CNDWRKRLPT
260 270 280 290 300
QIVLSSLLQK IMLPGCSLLL ELGQISVPKI RHLLKYPRVI TMQGFSERSV
310 320 330 340 350
EFYCMSFFDN QRGIEVAENL RNNEVLHLCS NPYLCWMFCS CLKWQFDREE
360 370 380 390 400
EGYFKAKTDA AFFTNFMVSA FKSTYAHSPS KQNRARLKTL CTLAVEGMWK
410 420 430 440 450
ELFVFDSEDL RRNGISESDK AVWLKMQFLQ THGNHTVFYH PTLQSYFAAM
460 470 480 490 500
FYFLKQDKDI CVPVIGSIPQ LLGNMYARGQ TQWLQLGTFL FGLINEQVAA
510 520 530 540 550
LLQPCFGFIQ PIYVRQEIIC YFKCLGQQEC NEKLERSQTL FSCLRDSQEE
560 570 580 590 600
RFVRQVVDLL EEITVDISSS DVLSVTAYAL QKSSKLKKLH LHIQKTVFSE
610 620 630 640 650
IYCPDHCKTR TSIGKRRNTA EYWKTLCGIF CNLYVLDLDS CQFNKRAIQD
660 670 680 690 700
LCNSMSPTPT VPLTAFKLQS LSCSFMADFG DGSLFHTLLQ LPHLKYLNLY
710 720 730 740 750
GTYLSMDVTE KLCAALRCSA CRVEELLLGK CGISSKACGI IAISLINSKV
760 770 780 790 800
KHLSLVENPL KNKGVMSLCE MLKDPSCVLQ SLMLSYCCLT FIACGHLYEA
810 820 830 840 850
LLSNKHLSLL DLGSNFLEDT GVNLLCEALK DPNCTLKELW LPGCFLTSQC
860 870 880 890 900
CEEISAVLIC NRNLKTLKLG NNNIQDTGVR QLCEALSHPN CNLECLGLDL
910 920 930 940 950
CEFTSDCCKD LALALTTCKT LNSLNLDWKT LDHSGLVVLC EALNHKRCNL
960 970 980 990 1000
KMLGLDKSAF SEESQTLLQD VEKKNNNLNI LHHPWFEAER NKRGTRLVWN

SRN
Length:1,003
Mass (Da):114,802
Last modified:October 11, 2004 - v1
Checksum:iCDC853C75A26EC91
GO
Isoform 2 (identifier: Q66X22-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     178-617: Missing.
     842-898: Missing.
     955-1003: LDKSAFSEES...GTRLVWNSRN → SGELMFLMKW...FYGERLTWHS

Note: No experimental confirmation available.
Show »
Length:501
Mass (Da):56,766
Checksum:i298748FDAD7C7640
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_025024178 – 617Missing in isoform 2. 1 PublicationAdd BLAST440
Alternative sequenceiVSP_025025842 – 898Missing in isoform 2. 1 PublicationAdd BLAST57
Alternative sequenceiVSP_025026955 – 1003LDKSA…WNSRN → SGELMFLMKWKDSDEADLVQ AKEANMICPQIVISFYGERL TWHS in isoform 2. 1 PublicationAdd BLAST49

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY596196 mRNA. Translation: AAU06317.1.
AY360471 mRNA. Translation: AAQ64009.1.
CCDSiCCDS20920.1. [Q66X22-1]
RefSeqiNP_918947.2. NM_194058.2. [Q66X22-1]
XP_006540001.1. XM_006539938.2. [Q66X22-1]
XP_006540002.1. XM_006539939.2. [Q66X22-1]
UniGeneiMm.277114.

Genome annotation databases

EnsembliENSMUST00000073151; ENSMUSP00000072895; ENSMUSG00000060508. [Q66X22-1]
ENSMUST00000117909; ENSMUSP00000113762; ENSMUSG00000060508. [Q66X22-2]
GeneIDi243874.
KEGGimmu:243874.
UCSCiuc009fnt.1. mouse. [Q66X22-1]
uc012fbm.1. mouse. [Q66X22-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiNLR9B_MOUSE
AccessioniPrimary (citable) accession number: Q66X22
Secondary accession number(s): Q6UTW9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 2007
Last sequence update: October 11, 2004
Last modified: September 27, 2017
This is version 112 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot