lmmol · Proteins

NACHT, LRR and PYD domains-containing protein 3

UniProt Q8R4B8 Organism Mus musculus Gene Cias1, Mmig1, Nalp3, Nlrp3, Pypaf1 EC 3.6.4.-

Also known as: Cias1, Mmig1, Nalp3, Nlrp3, Pypaf1

Function

Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyroptosis. In response to pathogens and other damage-associated signals that affect the integrity of membranes, initiates the formation of the inflammasome polymeric complex composed of NLRP3, CASP1 and PYCARD/ASC. Recruitment of pro-caspase-1 (proCASP1) to the NLRP3 inflammasome promotes caspase-1 (CASP1) activation, which subsequently cleaves and activates inflammatory cytokines IL1B and IL18 and gasdermin-D (GSDMD), promoting cytokine secretion and pyroptosis. Activation of NLRP3 inflammasome is also required for HMGB1 secretion; stimulating inflammatory responses. Involved in the homeostatic wound healing response to tissue injury, a multistep cascade that guides neutrophil migration to necrotic sites while avoiding collateral damage of healthy tissues. ATP released from necrotic cells triggers activation of NLRP3 inflammasome through P2RX7 signaling leading to neutrophil adhesion to the vascular endothelium close to the injury site. Under resting conditions, ADP-bound NLRP3 is autoinhibited (By similarity). NLRP3 activation stimuli include extracellular ATP, nigericin, reactive oxygen species, crystals of monosodium urate or cholesterol, amyloid-beta fibers, environmental or industrial particles and nanoparticles, such as asbestos, silica, aluminum salts, cytosolic dsRNA, etc. Almost all stimuli trigger intracellular K(+) efflux. These stimuli lead to membrane perturbation and activation of NLRP3 (By similarity). Upon activation, NLRP3 is transported to microtubule organizing center (MTOC), where it is unlocked by NEK7, leading to its relocalization to dispersed trans-Golgi network (dTGN) vesicle membranes and formation of an active inflammasome complex. Associates with dTGN vesicle membranes by binding to phosphatidylinositol 4-phosphate (PtdIns4P). Shows ATPase activity.

Classification

Family (Pfam)
PF14484 FISNA, PF13516 LRR_6, PF05729 NACHT, PF17776 NLRC4_HD2, PF02758 PYRIN, PF17779 WHD_NOD2
InterPro
DAPIN, DEATH-like_dom_sf, Leu-rich_rpt, LRR_dom_sf, NACHT-assoc, NACHT_NTPase, NLRP_HD2, NLRP_innate_immun_reg, NOD1/2_WH, P-loop_NTPase
Functional cluster
Immunoglobulin & Immune-Response Proteins

Experimental structures · PDB · 2

A predicted model is available from AlphaFold.

Gene Ontology · 65

Neighborhood · nearest proteins

Cias1Nlrp3C1orf7NLRP3Nek7Il1bBrcc3
Nearest neighbours of NACHT, LRR and PYD domains-containing protein 3: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 49 cited papers

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