Nucleotide-binding oligomerization domain-containing protein 3 (NLRC3) (NLRC3)

Nucleotide-binding oligomerization domain-containing protein 3 (NOD3), widely referred to as NLRC3, is a cytosolic protein belonging to the NOD-like receptor (NLR) family that serves as a critical negative regulator of innate immune signaling [1]. Unlike many other NLRs that promote inflammatory responses, NLRC3 acts to dampen the immune system by inhibiting the cGAS-STING pathway and the Toll-like receptor (TLR)-induced NF-kappaB activation [2, 3]. It achieves this by directly interacting with and sequestering key signaling molecules like STING and TRAF6, thereby preventing the overproduction of pro-inflammatory cytokines and type I interferons [2, 3]. In clinical research, NLRC3 is recognized as a significant tumor suppressor, particularly in colorectal cancer, where its downregulation is associated with increased cellular proliferation and tumor progression [4]. While there are currently no FDA-approved drugs that specifically target NLRC3, it is a subject of intense study for the development of therapies for autoimmune diseases and cancer immunotherapy [1, 4]. Sources: [1] UniProt (Q7RTR2): NLRC3_HUMAN. [2] Zhang, L., et al. (2014). NLRC3, a member of the NLR family of proteins, is a negative regulator of innate immune signaling induced by the DNA sensor STING. Immunity. [3] Schneider, M., et al. (2012). The innate immune sensor NLRC3 attenuates Toll-like receptor signaling via modification of the signaling adaptor TRAF6. Nature Immunology. [4] Karki, R., et al. (2016). NLRC3 regulates cellular proliferation and apoptosis to inhibit the development of colorectal cancer. Cell Host & Microbe.

Other names

NOD3CLR16.1NOD-like receptor C3Caterpiller protein 16.1

Negative regulation of the cGAS-STING and TLR-mediated NF-kappaB signaling pathways through direct interaction with signaling adaptors like STING and TRAF6.