NLRP6
entrez
171389
canonical
uniprot
P59044
canonical
ensembl
ENSG00000174885
resolver
ensp
ENSP00000309767
resolver
ensp
ENSP00000433617
resolver
genesymbol
NLRP6
resolver
genesymbol_syn
NALP6
resolver
genesymbol_syn
PYPAF5
resolver
hgnc
HGNC:22944
resolver
uniprot
A8K9F3
resolver
uniprot
E9PJZ8
resolver
uniprot_entry
NLRP6_HUMAN
resolver
uniprot_sec
A8K9F3
resolver
uniprot_sec
E9PJZ8
resolver
amino_acid_sequence
MDQPEAPCSSTGPRLAVARELLLAALEELSQEQLKRFRHKLRDVGPDGRSIPWGRLERADAVDLAEQLAQFYGPEPALEVARKTLKRADARDVAAQLQERRLQRLGLGSGTLLSVSEYKKKYREHVLQLHARVKERNARSVKITKRFTKLLIAPESAAPEEAMGPAEEPEPGRARRSDTHTFNRLFRRDEEGRRPLTVVLQGPAGIGKTMAAKKILYDWAAGKLYQGQVDFAFFMPCGELLERPGTRSLADLILDQCPDRGAPVPQMLAQPQRLLFILDGADELPALGGPEAAPCTDPFEAASGARVLGGLLSKALLPTALLLVTTRAAAPGRLQGRLCSPQCAEVRGFSDKDKKKYFYKYFRDERRAERAYRFVKENETLFALCFVPFVCWIVCTVLRQQLELGRDLSRTSKTTTSVYLLFITSVLSSAPVADGPRLQGDLRNLCRLAREGVLGRRAQFAEKELEQLELRGSKVQTLFLSKKELPGVLETEVTYQFIDQSFQEFLAALSYLLEDGGVPRTAAGGVGTLLRGDAQPHSHLVLTTRFLFGLLSAERMRDIERHFGCMVSERVKQEALRWVQGQGQGCPGVAPEVTEGAKGLEDTEEPEEEEEGEEPNYPLELLYCLYETQEDAFVRQALCRFPELALQRVRFCRMDVAVLSYCVRCCPAGQALRLISCRLVAAQEKKKKSLGKRLQASLGGGSSSQGTTKQLPASLLHPLFQAMTDPLCHLSSLTLSHCKLPDAVCRDLSEALRAAPALTELGLLHNRLSEAGLRMLSEGLAWPQCRVQTVRVQLPDPQRGLQYLVGMLRQSPALTTLDLSGCQLPAPMVTYLCAVLQHQGCGLQTLSLASVELSEQSLQELQAVKRAKPDLVITHPALDGHPQPPKELISTF
uniprot
proteins
function
FUNCTION: 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:30392956, 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:30674671). 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:30392956, PubMed:33377178, 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:31932628, 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 pro-inflammatory caspases (CASP1 and/or CASP4) that catalyze maturation and secretion of IL1B and IL18 in the extracellular milieu (PubMed:12387869, PubMed:30392956, PubMed:30674671, PubMed:34678144). The NLRP6 inflammasome plays a central role in the maintenance of epithelial integrity and host defense against microbial infections in the intestine (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, PubMed:33377178). 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:34161762, PubMed:34678144). Required to prevent infection by the apicomplexan parasite Cryptosporidium in enterocytes by promoting GSDMD-dependent release of IL18 (By similarity). 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 (By similarity). Essential for gut mucosal self-renewal and proliferation (By similarity). Regulate mucus secretion in an inflammasome- and autophagy-dependent manner to prevent invasion by enteric bacteria, (By similarity). During systemic bacterial infections, the NLRP6 inflammasome negatively regulates neutrophil recruitment and neutrophil extracellular traps (NETs) formation (By similarity). May promote peripheral nerve recovery following injury via an inflammasome-independent mechanism (By similarity). {ECO:0000250|UniProtKB:Q91WS2, ECO:0000269|PubMed:12387869, ECO:0000269|PubMed:30392956, ECO:0000269|PubMed:30674671, ECO:0000269|PubMed:31932628, ECO:0000269|PubMed:33377178, ECO:0000269|PubMed:34161762, ECO:0000269|PubMed:34678144}.
uniprot
proteins
mass_dalton
98768
uniprot
proteins
mutagenesis
MUTAGEN 21; /note="L->R: Decreased formation of an inflammasome filament."; /evidence="ECO:0000269|PubMed:30674671"; MUTAGEN 23; /note="L->R: Decreased formation of an inflammasome filament. Decreased ability to promote PYCARD/ASC polymerization."; /evidence="ECO:0000269|PubMed:30674671"; MUTAGEN 27..28; /note="EE->RR: Abolished formation of an inflammasome filament."; /evidence="ECO:0000269|PubMed:30674671"; MUTAGEN 39; /note="H->R: Decreased formation of an inflammasome filament. Abolished ability to promote PYCARD/ASC polymerization."; /evidence="ECO:0000269|PubMed:30674671"; MUTAGEN 42; /note="R->E: Abolished formation of an inflammasome filament."; /evidence="ECO:0000269|PubMed:30674671"; MUTAGEN 53; /note="W->E: Abolished formation of an inflammasome filament."; /evidence="ECO:0000269|PubMed:30674671"; MUTAGEN 53; /note="W->F: Does not affect formation of an inflammasome filament."; /evidence="ECO:0000269|PubMed:30674671"; MUTAGEN 71; /note="F->R: Does not prevent formation of an inflammasome filament."; /evidence="ECO:0000269|PubMed:30674671"; MUTAGEN 87; /note="R->D: Does not prevent formation of an inflammasome filament."; /evidence="ECO:0000269|PubMed:30674671"; MUTAGEN 352..356; /note="KDKKK->ADAAA: Impaired formation of liquid-liquid phase separation (LLPS)."; /evidence="ECO:0000269|PubMed:34678144
uniprot
proteins
post_translational_modification
PTM: Polyubiquitinated with 'Lys-63'-linked chains, promoting the interaction with PYCARD/ASC and formation of the NLRP6 inflammasome. Deubiquitination by CYLD decreases the interaction with PYCARD/ASC. {ECO:0000250|UniProtKB:Q91WS2}.
uniprot
proteins
protein_family
NLRP family
uniprot
proteins
pubmed
12019269
uniprot
proteins
pubmed
12387869
uniprot
proteins
pubmed
12563287
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
21088234
uniprot
proteins
pubmed
21593405
uniprot
proteins
pubmed
23470617
uniprot
proteins
pubmed
26282398
uniprot
proteins
pubmed
30392956
uniprot
proteins
pubmed
30674671
uniprot
proteins
pubmed
31932628
uniprot
proteins
pubmed
33377178
uniprot
proteins
pubmed
34161762
uniprot
proteins
pubmed
34678144
uniprot
proteins
sequence_length
892
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:12387869, ECO:0000269|PubMed:31932628}. Inflammasome {ECO:0000269|PubMed:12387869, ECO:0000269|PubMed:30674671, ECO:0000269|PubMed:31932628, ECO:0000269|PubMed:34678144}. Cell membrane {ECO:0000250|UniProtKB:Q63035}. Nucleus membrane {ECO:0000250|UniProtKB:Q63035}.
uniprot
proteins