UniProtKB - Q91WS2 (NLRP6_MOUSE)
NACHT, LRR and PYD domains-containing protein 6
Nlrp6
Functioni
Acts as the sensor component of the NLRP6 inflammasome, which mediates inflammasome activation in response to various pathogen-associated signals, leading to maturation and secretion of IL1B and IL18 (PubMed:21593405, PubMed:30392956, PubMed:32424362, PubMed:34678144).
Inflammasomes are supramolecular complexes that assemble in the cytosol in response to pathogens and other damage-associated signals and play critical roles in innate immunity and inflammation (PubMed:30392956).
Acts as a recognition receptor (PRR): recognizes and binds specific pathogens and other damage-associated signals, such as lipoteichoic acid (LTA), a cell-wall component of Gram-positive bacteria, or double stranded RNA (dsRNA) (PubMed:26494172, PubMed:30392956, PubMed:34678144).
May also recognize and bind lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria; however, LPS is probably not a major activator of the NLRP6 inflammasome (PubMed:34678144).
Following LTA- or dsRNA-binding, NLRP6 undergoes liquid-liquid phase separation (LLPS), enhancing multivalent interactions, an essential step for the formation of the NLRP6 inflammasome polymeric complex (PubMed:34678144).
The NLRP6 inflammasome acts by promoting recruitment of effector proinflammatory caspases (CASP1 and/or CASP4) that catalyze maturation and secretion of IL1B and IL18 in the extracellular milieu (PubMed:30392956).
The NLRP6 inflammasome plays a central role in the maintenance of epithelial integrity and host defense against microbial infections in the intestine (PubMed:21565393, PubMed:22763455, PubMed:23696660, PubMed:26638072, PubMed:28445725, PubMed:30392956).
Required to restrict infection against Gram-positive bacteria by recognizing lipoteichoic acid (LTA), leading to recruitment of CASP4 and CASP1, and subsequent maturation and secretion of IL1B and IL18 (PubMed:30392956).
Involved in intestinal antiviral innate immunity together with DHX15: recognizes and binds viral dsRNA to restrict infection by enteric viruses through the interferon pathway and GSDMD-dependent release of IL18 (PubMed:26494172, PubMed:34678144).
Required to prevent infection by the apicomplexan parasite C.tyzzeri in enterocytes by promoting GSDMD-dependent release of IL18 (PubMed:33372132).
The NLRP6 inflammasome may also regulate the gut microbiota composition by acting as a sensor of microbiota-associated metabolites to form a PYCARD/ASC-dependent inflammasome for downstream IL18 release and secretion of antimicrobial peptides (PubMed:21565393, PubMed:22763455, PubMed:26638072, PubMed:33617596).
Its role in the regulation of the gut microbiota composition is however subject to discussion (PubMed:29281815, PubMed:29281837, PubMed:28801232).
Essential for gut mucosal self-renewal and proliferation (PubMed:21593405, PubMed:21543645, PubMed:21565393).
Regulate mucus secretion in an inflammasome- and autophagy-dependent manner to prevent invasion by enteric bacteria (PubMed:24581500, PubMed:27339979).
During systemic bacterial infections, the NLRP6 inflammasome negatively regulates neutrophil recruitment and neutrophil extracellular traps (NETs) formation (PubMed:22763455, PubMed:30248149, PubMed:33918100, PubMed:33230225).
May promote peripheral nerve recovery following injury via an inflammasome-independent mechanism (PubMed:26253422).
22 PublicationsCaution
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 200 – 207 | ATPPROSITE-ProRule annotation | 8 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- peptide binding Source: MGI
- vasopressin receptor activity Source: UniProtKB
GO - Biological processi
- activation of cysteine-type endopeptidase activity Source: MGI
- acute inflammatory response Source: MGI
- acute inflammatory response to antigenic stimulus Source: MGI
- innate immune response Source: UniProtKB-KW
- necroptotic process Source: MGI
- negative regulation of ERK1 and ERK2 cascade Source: CACAO
- negative regulation of I-kappaB kinase/NF-kappaB signaling Source: CACAO
- negative regulation of immune response Source: MGI
- negative regulation of inflammatory response to antigenic stimulus Source: CACAO
- negative regulation of interferon-gamma production Source: MGI
- negative regulation of MAPK cascade Source: MGI
- negative regulation of toll-like receptor signaling pathway Source: MGI
- neutrophil-mediated killing of gram-positive bacterium Source: MGI
- pyroptosis Source: MGI
- regulation of autophagy Source: MGI
- regulation of inflammatory response Source: UniProtKB
- regulation of mucus secretion Source: MGI
- response to bacterium Source: MGI
- wound healing Source: MGI
Keywordsi
Biological process | Immunity, Inflammatory response, Innate immunity |
Ligand | ATP-binding, Nucleotide-binding |
Names & Taxonomyi
Protein namesi | Recommended name: NACHT, LRR and PYD domains-containing protein 6CuratedAlternative name(s): Angiotensin II/vasopressin receptor1 Publication Non-angiotensin-vasopressin receptor1 Publication Short name: Non-AVR1 Publication PYRIN-containing APAF1-like protein 5-like1 Publication |
Gene namesi | |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:2141990, Nlrp6 |
VEuPathDBi | HostDB:ENSMUSG00000038745 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm By similarity
- Inflammasome 2 Publications
Cytoplasm and Cytosol
- Cytoplasm By similarity
- Inflammasome By similarity
Plasma membrane
- Cell membrane By similarity
Nucleus
- Nucleus membrane By similarity
Cytoplasm and Cytosol
- Cytoplasm By similarity
Plasma membrane
- Cell membrane By similarity
Note: Predominantly expressed in the cell membrane.By similarity
Cytosol
- inflammasome complex Source: MGI
Nucleus
- nuclear membrane Source: UniProtKB-SubCell
Plasma Membrane
- plasma membrane Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cell membrane, Cytoplasm, Inflammasome, Membrane, NucleusPathology & Biotechi
Disruption phenotypei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 170 – 173 | RARR → AAAA: Does not affect formation of liquid-liquid phase separation (LLPS). 1 Publication | 4 | |
Mutagenesisi | 350 – 354 | KDKKK → ADAAA: Impaired formation of liquid-liquid phase separation (LLPS), leading to reduced formation of the NLRP6 inflammasome and GSDMD-dependent release of IL18. 1 Publication | 5 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000080893 | 1 – 869 | NACHT, LRR and PYD domains-containing protein 6Add BLAST | 869 |
Post-translational modificationi
Keywords - PTMi
Ubl conjugationProteomic databases
MaxQBi | Q91WS2 |
PaxDbi | Q91WS2 |
PeptideAtlasi | Q91WS2 |
PRIDEi | Q91WS2 |
ProteomicsDBi | 253083 [Q91WS2-1] 253084 [Q91WS2-2] 253085 [Q91WS2-3] |
PTM databases
PhosphoSitePlusi | Q91WS2 |
Expressioni
Tissue specificityi
Developmental stagei
Inductioni
Gene expression databases
Bgeei | ENSMUSG00000038745, Expressed in liver and 94 other tissues |
Genevisiblei | Q91WS2, MM |
Interactioni
Subunit structurei
Homomultimer; forms the NLRP6 inflammasome polymeric complex, a filament composed of homopolymers in response to pathogens and other damage-associated signals (PubMed:34678144). The core of NLRP6 inflammasomes consists of a signal sensor component (NLRP6), an adapter (PYCARD/ASC), which recruits effector proinflammatory caspases (CASP1 and CASP4) (PubMed:34678144).
Interacts (via pyrin domain) with PYCARD/ASC (via pyrin domain); interaction takes place following NLRP6 activation and formation of liquid-liquid phase separation (LLPS), initiating nucleation which greatly enhances further addition of soluble PYCARD/ASC molecules to the speck in a prion-like polymerization process (PubMed:32424362, PubMed:34678144). Clustered PYCARD/ASC nucleates the formation of CASP1 (or possibly CASP4) filaments through the interaction of their respective CARD domains, acting as a platform for CASP1 polymerization (PubMed:34678144). CASP1 filament formation increases local enzyme concentration, resulting in trans-autocleavage and activation (PubMed:34678144). Active CASP1 then processes IL1B and IL18 precursors, leading to the release of mature cytokines in the extracellular milieu and inflammatory response (PubMed:34678144).
Interacts with DHX15 (PubMed:26494172).
3 PublicationsBinary interactionsi
Q91WS2
With | #Exp. | IntAct |
---|---|---|
Dhx15 [O35286] | 2 | EBI-16182145,EBI-8322087 |
Isoform 1 [Q91WS2-1]
With | #Exp. | IntAct |
---|---|---|
DHX15 [O43143] from Homo sapiens. | 2 | EBI-16182226,EBI-1237044 |
MAVS - isoform 1 [Q7Z434-1] from Homo sapiens. | 2 | EBI-16182226,EBI-15577799 |
Protein-protein interaction databases
DIPi | DIP-61874N |
IntActi | Q91WS2, 3 interactors |
STRINGi | 10090.ENSMUSP00000139170 |
Miscellaneous databases
RNActi | Q91WS2, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 37 – 128 | PyrinPROSITE-ProRule annotationAdd BLAST | 92 | |
Domaini | 194 – 511 | NACHTPROSITE-ProRule annotationAdd BLAST | 318 | |
Repeati | 460 – 485 | LRR 1Sequence analysisAdd BLAST | 26 | |
Repeati | 635 – 658 | LRR 2Sequence analysisAdd BLAST | 24 | |
Repeati | 837 – 860 | LRR 3Sequence analysisAdd BLAST | 24 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 350 – 354 | Disordered1 Publication | 5 | |
Regioni | 577 – 608 | DisorderedSequence analysisAdd BLAST | 32 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Leucine-rich repeat, RepeatPhylogenomic databases
eggNOGi | ENOG502SANB, Eukaryota |
GeneTreei | ENSGT00940000162758 |
HOGENOMi | CLU_002274_2_2_1 |
InParanoidi | Q91WS2 |
OMAi | GLAWPRC |
OrthoDBi | 114368at2759 |
PhylomeDBi | Q91WS2 |
Family and domain databases
Gene3Di | 1.10.533.10, 1 hit 3.40.50.300, 1 hit 3.80.10.10, 1 hit |
InterProi | View protein in InterPro IPR004020, DAPIN IPR011029, DEATH-like_dom_sf IPR032675, LRR_dom_sf IPR007111, NACHT_NTPase IPR041267, NLRP_HD2 IPR041075, NOD2_WH IPR027417, P-loop_NTPase |
Pfami | View protein in Pfam PF05729, NACHT, 1 hit PF17776, NLRC4_HD2, 1 hit PF17779, NOD2_WH, 1 hit PF02758, PYRIN, 1 hit |
SMARTi | View protein in SMART SM01289, PYRIN, 1 hit |
SUPFAMi | SSF47986, SSF47986, 1 hit SSF52540, SSF52540, 1 hit |
PROSITEi | View protein in PROSITE PS50824, DAPIN, 1 hit PS50837, NACHT, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative promoter usage and alternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MDAAGASCSS VDAVARELLM ATLEELSQEQ LKRFRHKLRD APLDGRSIPW
60 70 80 90 100
GRLERSDAVD LVDKLIEFYE PVPAVEMTRQ VLKRSDIRDV ASRLKQQQLQ
110 120 130 140 150
KLGPTSVLLS VSAFKKKYRE HVLRQHAKVK ERNARSVKIN KRFTKLLIAP
160 170 180 190 200
GTGAVEDELL GPLGEPEPER ARRSDTHTFN RLFRGNDEES SQPLTVVLQG
210 220 230 240 250
PAGIGKTMAA KKILYDWAAG KLYHSQVDFA FFMPCGELLE RPGKRSLADL
260 270 280 290 300
VLDQCPDRAW PVKRILAQPN RLLFILDGAD ELPTLPSSEA TPCKDPLEAT
310 320 330 340 350
SGLRVLSGLL SQELLPGARL LVTTRHAATG RLQGRLCSPQ CAEIRGFSDK
360 370 380 390 400
DKKKYFFKFF RDERKAERAY RFVKENETLF ALCFVPFVCW IVCTVLQQQL
410 420 430 440 450
ELGRDLSRTS KTTTSVYLLF ITSMLKSAGT NGPRVQGELR TLCRLAREGI
460 470 480 490 500
LDHHKAQFSE EDLEKLKLRG SQVQTIFLNK KEIPGVLKTE VTYQFIDQSF
510 520 530 540 550
QEFLAALSYL LEAERTPGTP AGGVQKLLNS DAELRGHLAL TTRFLFGLLN
560 570 580 590 600
TEGLRDIGNH FGCVVPDHVK KDTLRWVQGQ SHPKGPPVGA KKTAELEDIE
610 620 630 640 650
DAEEEEEEEE DLNFGLELLY CLYETQEEDF VRQALSSLPE IVLERVRLTR
660 670 680 690 700
MDLEVLNYCV QCCPDGQALR LVSCGLVAAK EKKKKKKSLV KRLKGSQSTK
710 720 730 740 750
KQPPVSLLRP LCETMTTPKC HLSVLILSHC RLPDAVCRDL SEALKVAPAL
760 770 780 790 800
RELGLLQSRL TNTGLRLLCE GLAWPKCQVK TLRMQLPDLQ EVINYLVIVL
810 820 830 840 850
QQSPVLTTLD LSGCQLPGVI VEPLCAALKH PKCSLKTLSL TSVELSENSL
860
RDLQAVKTSK PDLSIIYSK
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketE9QNS0 | E9QNS0_MOUSE | NACHT, LRR and PYD domains-containi... | Nlrp6 | 882 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 429 | G → F in ACN32212 (PubMed:20923861).Curated | 1 | |
Sequence conflicti | 454 | Missing in ACN32212 (PubMed:20923861).Curated | 1 | |
Sequence conflicti | 733 | P → R in ACN32212 (PubMed:20923861).Curated | 1 | |
Sequence conflicti | 869 | K → KIRHTSPASEG in ACN32212 (PubMed:20923861).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_042301 | 1 – 423 | Missing in isoform 2. 2 PublicationsAdd BLAST | 423 | |
Alternative sequenceiVSP_057971 | 1 – 9 | MDAAGASCS → MYCPGAPCGECAMCDPGCFG GSGTGPIQVASVMITLLIP in isoform 3. | 9 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | JF810536 mRNA Translation: AEI54131.1 AC107815 Genomic DNA No translation available. AC162287 Genomic DNA No translation available. BC013519 mRNA Translation: AAH13519.1 BC031139 mRNA Translation: AAH31139.1 FJ222825 mRNA Translation: ACN32212.1 Frameshift. AY355343 mRNA Translation: AAR14740.1 |
CCDSi | CCDS40178.2 [Q91WS2-1] |
RefSeqi | NP_598707.2, NM_133946.2 [Q91WS2-1] XP_006536212.1, XM_006536149.3 [Q91WS2-3] |
Genome annotation databases
Ensembli | ENSMUST00000183845; ENSMUSP00000139357; ENSMUSG00000038745 [Q91WS2-1] ENSMUST00000184560; ENSMUSP00000139170; ENSMUSG00000038745 [Q91WS2-3] |
GeneIDi | 101613 |
KEGGi | mmu:101613 |
UCSCi | uc009kiv.3, mouse [Q91WS2-1] uc029wpm.2, mouse |
Keywords - Coding sequence diversityi
Alternative promoter usage, Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | JF810536 mRNA Translation: AEI54131.1 AC107815 Genomic DNA No translation available. AC162287 Genomic DNA No translation available. BC013519 mRNA Translation: AAH13519.1 BC031139 mRNA Translation: AAH31139.1 FJ222825 mRNA Translation: ACN32212.1 Frameshift. AY355343 mRNA Translation: AAR14740.1 |
CCDSi | CCDS40178.2 [Q91WS2-1] |
RefSeqi | NP_598707.2, NM_133946.2 [Q91WS2-1] XP_006536212.1, XM_006536149.3 [Q91WS2-3] |
3D structure databases
SMRi | Q91WS2 |
ModBasei | Search... |
Protein-protein interaction databases
DIPi | DIP-61874N |
IntActi | Q91WS2, 3 interactors |
STRINGi | 10090.ENSMUSP00000139170 |
PTM databases
PhosphoSitePlusi | Q91WS2 |
Proteomic databases
MaxQBi | Q91WS2 |
PaxDbi | Q91WS2 |
PeptideAtlasi | Q91WS2 |
PRIDEi | Q91WS2 |
ProteomicsDBi | 253083 [Q91WS2-1] 253084 [Q91WS2-2] 253085 [Q91WS2-3] |
Protocols and materials databases
Antibodypediai | 58845, 237 antibodies from 29 providers |
DNASUi | 101613 |
Genome annotation databases
Ensembli | ENSMUST00000183845; ENSMUSP00000139357; ENSMUSG00000038745 [Q91WS2-1] ENSMUST00000184560; ENSMUSP00000139170; ENSMUSG00000038745 [Q91WS2-3] |
GeneIDi | 101613 |
KEGGi | mmu:101613 |
UCSCi | uc009kiv.3, mouse [Q91WS2-1] uc029wpm.2, mouse |
Organism-specific databases
CTDi | 171389 |
MGIi | MGI:2141990, Nlrp6 |
VEuPathDBi | HostDB:ENSMUSG00000038745 |
Phylogenomic databases
eggNOGi | ENOG502SANB, Eukaryota |
GeneTreei | ENSGT00940000162758 |
HOGENOMi | CLU_002274_2_2_1 |
InParanoidi | Q91WS2 |
OMAi | GLAWPRC |
OrthoDBi | 114368at2759 |
PhylomeDBi | Q91WS2 |
Miscellaneous databases
BioGRID-ORCSi | 101613, 1 hit in 65 CRISPR screens |
PROi | PR:Q91WS2 |
RNActi | Q91WS2, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000038745, Expressed in liver and 94 other tissues |
Genevisiblei | Q91WS2, MM |
Family and domain databases
Gene3Di | 1.10.533.10, 1 hit 3.40.50.300, 1 hit 3.80.10.10, 1 hit |
InterProi | View protein in InterPro IPR004020, DAPIN IPR011029, DEATH-like_dom_sf IPR032675, LRR_dom_sf IPR007111, NACHT_NTPase IPR041267, NLRP_HD2 IPR041075, NOD2_WH IPR027417, P-loop_NTPase |
Pfami | View protein in Pfam PF05729, NACHT, 1 hit PF17776, NLRC4_HD2, 1 hit PF17779, NOD2_WH, 1 hit PF02758, PYRIN, 1 hit |
SMARTi | View protein in SMART SM01289, PYRIN, 1 hit |
SUPFAMi | SSF47986, SSF47986, 1 hit SSF52540, SSF52540, 1 hit |
PROSITEi | View protein in PROSITE PS50824, DAPIN, 1 hit PS50837, NACHT, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | NLRP6_MOUSE | |
Accessioni | Q91WS2Primary (citable) accession number: Q91WS2 Secondary accession number(s): C9W978 Q8K0L4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 28, 2003 |
Last sequence update: | August 21, 2007 | |
Last modified: | February 23, 2022 | |
This is version 160 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families