DegronMD - P59044(NLRP6)

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:34678144, PubMed:33377178). 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:30674671, PubMed:12387869, PubMed:30392956, 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:34678144, PubMed:34161762). 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}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.D189E	DO228787	GACA	ICGC	GRRPLTVVL	DEG_APCC_DBOX_1	192:200	Mutation rewiring degron network	0.25
p.G207S	DO229259	THCA	ICGC	GRRPLTVVL	DEG_APCC_DBOX_1	192:200	Mutation rewiring degron network	0.1389
p.R188S	DO229221	THCA	ICGC	GRRPLTVVL	DEG_APCC_DBOX_1	192:200	Mutation rewiring degron network	0.2222
p.R187H	SIDM00863	Burkitt's Lymphoma	GDSC	GRRPLTVVL	DEG_APCC_DBOX_1	192:200	Mutation rewiring degron network	0.1944
p.R187H	SIDM00774	Breast Carcinoma	GDSC	GRRPLTVVL	DEG_APCC_DBOX_1	192:200	Mutation rewiring degron network	0.1944
p.P13R	ACH-000612	Lymphoma	CCLE	PCSST	DEG_SPOP_SBC_1	7:11	Mutation rewiring degron network	0.2778

DegronMD: protein-targeted degradation, mutation and drug response to degrons

NLRP6

UniProt ID: P59044

Entrez ID: 171389

Protein name: NACHT, LRR and PYD domains-containing protein 6 (Angiotensin II/vasopressin receptor) (PYRIN-containing APAF1-like protein 5)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for NLRP6 in