NLRC3
Description
The NLRC3 (NLR family CARD domain containing 3) is a protein-coding gene located on chromosome 16.
NLRC3, short for NOD-like receptor family CARD domain containing 3, is an intracellular protein that plays a role in the immune system. It was previously known as nucleotide-binding oligomerization domain, leucine rich repeat and CARD domain containing 3 (NOD3) and CLR16.2. NLRC3 inhibits the activity of T cells. NLRC3 also inhibits the mTOR signalling pathway to block cellular proliferation.
NLRC3 is a negative regulator of the innate immune response. It attenuates signaling pathways activated by Toll-like receptors (TLRs) and the DNA sensor STING/TMEM173 in response to pathogen-associated molecular patterns, such as intracellular poly(dA:dT), but not poly(I:C), or in response to DNA virus infection, including that of Herpes simplex virus 1 (HSV1). NLRC3 may affect TLR4 signaling by acting at the level of TRAF6 ubiquitination, decreasing the activating 'Lys-63'-linked ubiquitination and leaving unchanged the degradative 'Lys-48'-linked ubiquitination. NLRC3 inhibits the PI3K-AKT-mTOR pathway possibly by directly interacting with the posphatidylinositol 3-kinase regulatory subunit p85 (PIK3R1/PIK3R2) and disrupting the association between PIK3R1/PIK3R2 and the catalytic subunit p110 (PIK3CA/PIK3CB/PIK3CD) and reducing PIK3R1/PIK3R2 activation. Through its regulation of the PI3K-AKT-mTOR pathway, NLRC3 controls cell proliferation, predominantly in intestinal epithelial cells. NLRC3 may also affect NOD1- or NOD2-mediated NF-kappa-B activation. It might also affect the inflammatory response by preventing NLRP3 inflammasome formation, CASP1 cleavage and IL1B maturation.
NLRC3 is also known as CLR16.2, NOD3.