Recombinant Mouse NACHT, LRR and PYD domains-containing protein 3 (Nlrp3), partial

Function

Independently of inflammasome activation, regulates the differentiation of T helper 2 (Th2) cells and has a role in Th2 cell-dependent asthma and tumor growth (PubMed:26098997). During Th2 differentiation, required for optimal IRF4 binding to IL4 promoter and for IRF4-dependent IL4 transcription (PubMed:26098997). Binds to the consensus DNA sequence 5'-GRRGGNRGAG-3' (PubMed:26098997). May also participate in the transcription of IL5, IL13, GATA3, CCR3, CCR4 and MAF (PubMed:26098997)

Subcellular Location

Cytoplasm, cytosol; Inflammasome; Cytoplasm, cytoskeleton, microtubule organizing center; Golgi apparatus membrane; Endoplasmic reticulum; Mitochondrion; Secreted; Nucleus

Tissue Specificity

Expressed with high levels in peripheral blood leukocytes, including Th2 lymphocytes and macrophages (PubMed:15302403, PubMed:16546100, PubMed:26098997, PubMed:28847925). Expressed at low levels in resting osteoblasts (at protein level) (PubMed:17907925)

Subunit

Sensor component of NLRP3 inflammasomes; 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:34861190). The core of NLRP3 inflammasomes consists of a signal sensor component (NLRP3), an adapter (PYCARD/ASC), which recruits an effector pro-inflammatory caspase (CASP1 and, possibly, CASP4 and CASP5) (PubMed:24630723). Homodecamer; inactive NLRP3 forms homodecameric double-ring cages that hide pyrin domains within NACHT-LRR rings to avoid premature activation (PubMed:34861190, PubMed:35254907). Interacts (via pyrin domain) with PYCARD/ASC (via pyrin domain); interaction is direct (PubMed:17907925, PubMed:30487600). Interacts (via LRR repeat domain) with NEK7 (via N-terminus); the interaction is required for the formation of the complex NLRP3:PYCARD, oligomerization of PYCARD/ASC and activation of CASP1 (PubMed:26553871, PubMed:26642356, PubMed:26814970, PubMed:34615873, PubMed:37001519). Interacts (via LRR repeat domain) with NR4A1/Nur77 (via N-terminus); the interaction is direct, requires activation of NR4A1 by its ligands NBRE-containing dsDNA and lipopolysaccharide, and stimulates the association of NLRP3 with NEK7 for non-canonical NLRP3 inflammasome activation (PubMed:37001519). Interacts with CARD8; leading to inhibit formation of the NLRP3 inflammasome (By similarity). Interacts with MEFV; this interaction targets NLRP3 to degradation by autophagy, hence preventing excessive IL1B- and IL18-mediated inflammation (By similarity). Interacts with EIF2AK2/PKR; this interaction requires EIF2AK2 activity, is accompanied by EIF2AK2 autophosphorylation and promotes inflammasome assembly in response to specific stimuli (PubMed:22801494). Interacts with GBP5 (via DAPIN domain); this interaction promotes inflammasome assembly in response to microbial and soluble, but not crystalline, agents (By similarity). Interacts with PML (isoform PML-1) (via the leucine-rich repeat (LRR) domain); PML-mediated increase in NLRP3 inflammasome activation does not depend upon this interaction (By similarity). Interacts (via NACHT domain) with DHX33 (via DEAH box); NLRP3 activation in presence of cytosolic dsRNA is mediated by DHX33 (By similarity). Interacts (via NACHT and LRR domains) with ARRB2; this interaction is direct and inducible by polyunsaturated fatty acids (PUFAs) (By similarity). Interacts (via NACHT domain) with DDX3X under both LPS-primed and inflammasome-activating conditions (PubMed:31511697). Interacts with IRF4 (via the LRR domain); this interaction is direct and is required for optimal IRF4 binding to IL4 promoter and efficient IL4 transactivation during differentiation of Th2 helper T cells (PubMed:26098997). Interacts with MAVS; promoting localization to mitochondria and activation of the NLRP3 inflammasome (PubMed:23582325). Interacts with MARK4; promoting localization of NLRP3 to the microtubule organizing center (MTOC) (PubMed:28656979). Interacts with TRIM50; this interaction also promotes NLRP3 oligomerization and subsequent inflammasome activation (PubMed:36178239). Interacts with IRGM; preventing NLRP3 inflammasome assembly and promoting NLRP3 degradation (By similarity). Interacts (via KFERQ-like motifs) with HSPA8/HSC70; promoting NLRP3 degradation by the chaperone-mediated autophagy pathway (By similarity). Interacts (via NACHT and LLR domains) with ABHD8; this interaction is enhanced in the presence of NLRP3 inflammasome inducers, such as ATP, nigericin, silica, or alum. Interaction with ABHD8 leads the recruitment of ZDHHC12, hence facilitating NLRP3 palmitoylation and degradation by the chaperone-mediated autophagy pathway (CMA), therefore attenuating NLRP3 inflammasome activation (By similarity). Interacts with ZNFX1; the interaction inhibits NLRP3 inflammasome activation by sequestering NLRP3 in the cytoplasm (By similarity). Interacts with FAM120A; this interaction inhibits inflammasome activation (By similarity)

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