ID  Q91WS2;
PN  NACHT, LRR and PYD domains-containing protein 6;
GN  Nlrp6;
OS  10090;
SL  Nucleus Position: SL-0178;
SL  Nucleus Position: SL-0182;
SL  Comments: Cytoplasm {ECO:0000250|UniProtKB:Q63035}. Inflammasome {ECO:0000269|PubMed:30248149, ECO:0000269|PubMed:34678144}. [Isoform 1]: Cytoplasm {ECO:0000250|UniProtKB:Q63035}. Inflammasome {ECO:0000250|UniProtKB:P59044}. Cell membrane {ECO:0000250|UniProtKB:Q63035}. Nucleus membrane {ECO:0000250|UniProtKB:Q63035}. [Isoform 2]: Cytoplasm {ECO:0000250|UniProtKB:Q63035}. Cell membrane {ECO:0000250|UniProtKB:Q63035}. Note=Predominantly expressed in the cell membrane. {ECO:0000250|UniProtKB:Q63035}.
DR  UNIPROT: Q91WS2;
DR  UNIPROT: C9W978;
DR  UNIPROT: F8UKQ6;
DR  UNIPROT: Q67EY0;
DR  UNIPROT: Q8K0L4;
DR  Pfam: PF05729;
DR  Pfam: PF17776;
DR  Pfam: PF17779;
DR  Pfam: PF02758;
DR  PROSITE: PS50824;
DR  PROSITE: PS50837;
DE  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: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 pro-inflammatory 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). {ECO:0000269|PubMed:21543645, ECO:0000269|PubMed:21565393, ECO:0000269|PubMed:21593405, ECO:0000269|PubMed:22763455, ECO:0000269|PubMed:23696660, ECO:0000269|PubMed:24581500, ECO:0000269|PubMed:26253422, ECO:0000269|PubMed:26494172, ECO:0000269|PubMed:26638072, ECO:0000269|PubMed:27339979, ECO:0000269|PubMed:28445725, ECO:0000269|PubMed:28801232, ECO:0000269|PubMed:29281815, ECO:0000269|PubMed:29281837, ECO:0000269|PubMed:30248149, ECO:0000269|PubMed:30392956, ECO:0000269|PubMed:32424362, ECO:0000269|PubMed:33230225, ECO:0000269|PubMed:33372132, ECO:0000269|PubMed:33617596, ECO:0000269|PubMed:33918100, ECO:0000269|PubMed:34678144}.
DE  Reference Proteome: Yes;
DE  Interaction: O35286; IntAct: EBI-16182259; Score: 0.44
DE  Interaction: O43143; IntAct: EBI-16182238; Score: 0.40
DE  Interaction: Q7Z434; IntAct: EBI-16182335; Score: 0.40
GO  GO:0005737;
GO  GO:0005829;
GO  GO:0061702;
GO  GO:0140738;
GO  GO:0043228;
GO  GO:0031965;
GO  GO:0005886;
GO  GO:0005524;
GO  GO:0003725;
GO  GO:0001530;
GO  GO:0070891;
GO  GO:0140693;
GO  GO:0038187;
GO  GO:0042277;
GO  GO:0005000;
GO  GO:0097202;
GO  GO:0002526;
GO  GO:0002438;
GO  GO:0140374;
GO  GO:0050830;
GO  GO:0051607;
GO  GO:0048874;
GO  GO:0070266;
GO  GO:0070373;
GO  GO:0043124;
GO  GO:0050777;
GO  GO:0002862;
GO  GO:0032689;
GO  GO:0043409;
GO  GO:0034122;
GO  GO:0070946;
GO  GO:0140739;
GO  GO:0050729;
GO  GO:2000494;
GO  GO:0051260;
GO  GO:0070269;
GO  GO:0010506;
GO  GO:0050727;
GO  GO:0070255;
GO  GO:0009617;
GO  GO:0042060;
TP  Membrane Topology: Unknown; Source: UniProt - Sequence Analysis;
SQ  MDAAGASCSSVDAVARELLMATLEELSQEQLKRFRHKLRDAPLDGRSIPWGRLERSDAVDLVDKLIEFYEPVPAVEMTRQ
SQ  VLKRSDIRDVASRLKQQQLQKLGPTSVLLSVSAFKKKYREHVLRQHAKVKERNARSVKINKRFTKLLIAPGTGAVEDELL
SQ  GPLGEPEPERARRSDTHTFNRLFRGNDEESSQPLTVVLQGPAGIGKTMAAKKILYDWAAGKLYHSQVDFAFFMPCGELLE
SQ  RPGKRSLADLVLDQCPDRAWPVKRILAQPNRLLFILDGADELPTLPSSEATPCKDPLEATSGLRVLSGLLSQELLPGARL
SQ  LVTTRHAATGRLQGRLCSPQCAEIRGFSDKDKKKYFFKFFRDERKAERAYRFVKENETLFALCFVPFVCWIVCTVLQQQL
SQ  ELGRDLSRTSKTTTSVYLLFITSMLKSAGTNGPRVQGELRTLCRLAREGILDHHKAQFSEEDLEKLKLRGSQVQTIFLNK
SQ  KEIPGVLKTEVTYQFIDQSFQEFLAALSYLLEAERTPGTPAGGVQKLLNSDAELRGHLALTTRFLFGLLNTEGLRDIGNH
SQ  FGCVVPDHVKKDTLRWVQGQSHPKGPPVGAKKTAELEDIEDAEEEEEEEEDLNFGLELLYCLYETQEEDFVRQALSSLPE
SQ  IVLERVRLTRMDLEVLNYCVQCCPDGQALRLVSCGLVAAKEKKKKKKSLVKRLKGSQSTKKQPPVSLLRPLCETMTTPKC
SQ  HLSVLILSHCRLPDAVCRDLSEALKVAPALRELGLLQSRLTNTGLRLLCEGLAWPKCQVKTLRMQLPDLQEVINYLVIVL
SQ  QQSPVLTTLDLSGCQLPGVIVEPLCAALKHPKCSLKTLSLTSVELSENSLRDLQAVKTSKPDLSIIYSK
//