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Protein

NACHT, LRR and PYD domains-containing protein 9

Gene

NLRP9

Organism
Homo sapiens (Human)
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 bindingi152 – 159ATPPROSITE-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 9
Alternative name(s):
Nucleotide-binding oligomerization domain protein 6
PYRIN and NACHT-containing protein 12
Gene namesi
Name:NLRP9
Synonyms:NALP9, NOD6, PAN12
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000185792.9.
HGNCiHGNC:22941. NLRP9.

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

Organism-specific databases

DisGeNETi338321.
OpenTargetsiENSG00000185792.
PharmGKBiPA162398029.

Polymorphism and mutation databases

BioMutaiNLRP9.
DMDMi74762418.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002863341 – 991NACHT, LRR and PYD domains-containing protein 9Add BLAST991

Proteomic databases

EPDiQ7RTR0.
PaxDbiQ7RTR0.
PeptideAtlasiQ7RTR0.
PRIDEiQ7RTR0.

PTM databases

iPTMnetiQ7RTR0.
PhosphoSitePlusiQ7RTR0.

Expressioni

Tissue specificityi

Expressed in ileum intestinal epithelial cells. Not detected in peripheral blood mononuclear cells (PubMed:28636595). Expressed in cerebral endothelial cells and, at much lower levels, in brain pericytes (PubMed:28432035).2 Publications

Inductioni

In brain pericytes, up-regulated at the mRNA level in response to oxidative stress.1 Publication

Gene expression databases

BgeeiENSG00000185792.
CleanExiHS_NLRP9.
GenevisibleiQ7RTR0. HS.

Organism-specific databases

HPAiHPA042623.

Interactioni

Subunit structurei

Sensor component of NLRP9 inflammasomes. Inflammasomes are supramolecular complexes that assemble in the cytosol in response to pathogens, such as rotavirus, 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 (PubMed:28636595). Interacts with DHX9 upon rotavirus infection; this interaction may trigger inflammasome activation and inflammatory response (PubMed:28636595).1 Publication

Protein-protein interaction databases

BioGridi130708. 5 interactors.
STRINGi9606.ENSP00000331857.

Structurei

3D structure databases

ProteinModelPortaliQ7RTR0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 94PyrinPROSITE-ProRule annotationAdd BLAST94
Domaini146 – 465NACHTPROSITE-ProRule annotationAdd BLAST320
Repeati743 – 763LRR 1Add BLAST21
Repeati772 – 793LRR 2Add BLAST22
Repeati800 – 820LRR 3Add BLAST21
Repeati829 – 850LRR 4Add BLAST22
Repeati857 – 877LRR 5Add BLAST21
Repeati886 – 907LRR 6Add BLAST22

Sequence similaritiesi

Belongs to the NLRP family.Curated

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiKOG4308. Eukaryota.
ENOG410ZBX3. LUCA.
GeneTreeiENSGT00860000133669.
HOGENOMiHOG000294064.
HOVERGENiHBG063656.
InParanoidiQ7RTR0.
OMAiRILFIMD.
OrthoDBiEOG091G01CG.
PhylomeDBiQ7RTR0.

Family and domain databases

Gene3Di3.80.10.10. 1 hit.
InterProiView protein in InterPro
IPR004020. DAPIN.
IPR011029. DEATH-like_dom.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
PfamiView protein in Pfam
PF13516. LRR_6. 3 hits.
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: Q7RTR0-1) [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
MAESFFSDFG LLWYLKELRK EEFWKFKELL KQPLEKFELK PIPWAELKKA
60 70 80 90 100
SKEDVAKLLD KHYPGKQAWE VTLNLFLQIN RKDLWTKAQE EMRNKLNPYR
110 120 130 140 150
KHMKETFQLI WEKETCLHVP EHFYKETMKN EYKELNDAYT AAARRHTVVL
160 170 180 190 200
EGPDGIGKTT LLRKVMLDWA EGNLWKDRFT FVFFLNVCEM NGIAETSLLE
210 220 230 240 250
LLSRDWPESS EKIEDIFSQP ERILFIMDGF EQLKFNLQLK ADLSDDWRQR
260 270 280 290 300
QPMPIILSSL LQKKMLPESS LLIALGKLAM QKHYFMLRHP KLIKLLGFSE
310 320 330 340 350
SEKKSYFSYF FGEKSKALKV FNFVRDNGPL FILCHNPFTC WLVCTCVKQR
360 370 380 390 400
LERGEDLEIN SQNTTYLYAS FLTTVFKAGS QSFPPKVNRA RLKSLCALAA
410 420 430 440 450
EGIWTYTFVF SHGDLRRNGL SESEGVMWVG MRLLQRRGDC FAFMHLCIQE
460 470 480 490 500
FCAAMFYLLK RPKDDPNPAI GSITQLVRAS VVQPQTLLTQ VGIFMFGIST
510 520 530 540 550
EEIVSMLETS FGFPLSKDLK QEITQCLESL SQCEADREAI AFQELFIGLF
560 570 580 590 600
ETQEKEFVTK VMNFFEEVFI YIGNIEHLVI ASFCLKHCQH LTTLRMCVEN
610 620 630 640 650
IFPDDSGCIS DYNEKLVYWR ELCSMFITNK NFQILDMENT SLDDPSLAIL
660 670 680 690 700
CKALAQPVCK LRKLIFTSVY FGHDSELFKA VLHNPHLKLL SLYGTSLSQS
710 720 730 740 750
DIRHLCETLK HPMCKIEELI LGKCDISSEV CEDIASVLAC NSKLKHLSLV
760 770 780 790 800
ENPLRDEGMT LLCEALKHSH CALERLMLMY CCLTSVSCDS ISEVLLCSKS
810 820 830 840 850
LSLLDLGSNA LEDNGVASLC AALKHPGCSI RELWLMGCFL TSDSCKDIAA
860 870 880 890 900
VLICNGKLKT LKLGHNEIGD TGVRQLCAAL QHPHCKLECL GLQTCPITRA
910 920 930 940 950
CCDDIAAALI ACKTLRSLNL DWIALDADAV VVLCEALSHP DCALQMLGLH
960 970 980 990
KSGFDEETQK ILMSVEEKIP HLTISHGPWI DEEYKIRGVL L
Length:991
Mass (Da):113,312
Last modified:December 15, 2003 - v1
Checksum:iB9DD003967AB93D9
GO
Isoform 2 (identifier: Q7RTR0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     949-991: LHKSGFDEET...EEYKIRGVLL → NCQKSLGDTV...NMQRQLRLQK

Show »
Length:986
Mass (Da):112,593
Checksum:iB4248B46F70413B2
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_036386425G → D in a breast cancer sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_025021949 – 991LHKSG…RGVLL → NCQKSLGDTVAPGENHCSIK HLLLTLPINMQRQLRLQK in isoform 2. 1 PublicationAdd BLAST43

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY154464 mRNA. Translation: AAO18160.1.
CH471135 Genomic DNA. Translation: EAW72412.1.
BC136583 mRNA. Translation: AAI36584.1.
BK001114 mRNA. Translation: DAA01247.1.
CCDSiCCDS12934.1. [Q7RTR0-1]
RefSeqiNP_789790.2. NM_176820.3. [Q7RTR0-1]
UniGeneiHs.661568.

Genome annotation databases

EnsembliENST00000332836; ENSP00000331857; ENSG00000185792. [Q7RTR0-1]
ENST00000590200; ENSP00000465253; ENSG00000185792. [Q7RTR0-2]
GeneIDi338321.
KEGGihsa:338321.
UCSCiuc002qly.3. human. [Q7RTR0-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNLRP9_HUMAN
AccessioniPrimary (citable) accession number: Q7RTR0
Secondary accession number(s): B2RN12, Q86W27
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 2007
Last sequence update: December 15, 2003
Last modified: September 27, 2017
This is version 126 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families