Nucleotide-binding oligomerization domain-containing protein (NOD) (NOD)

Nucleotide-binding oligomerization domain-containing proteins, primarily NOD1 and NOD2, are essential intracellular pattern recognition receptors (PRRs) that monitor the cytosolic environment for signs of bacterial invasion (UniProt: Q9Y239, Q9HB55). These proteins are characterized by a tripartite structure consisting of a C-terminal leucine-rich repeat (LRR) domain for ligand sensing, a central NACHT domain for oligomerization, and N-terminal caspase recruitment domains (CARDs) for downstream signaling (PubMed: 25633458). NOD1 and NOD2 detect specific fragments of bacterial peptidoglycan, such as meso-diaminopimelic acid and muramyl dipeptide, respectively. Upon activation, they recruit the kinase RIPK2, which triggers the NF-kappaB and MAPK pathways to initiate an inflammatory response and produce antimicrobial peptides (PubMed: 30104658). Mutations in the NOD2 gene are strongly linked to inflammatory diseases like Crohn's disease and Blau syndrome, highlighting their role in immune homeostasis (PubMed: 11346780). Consequently, these proteins are significant therapeutic targets; for example, the NOD2 agonist mifamurtide is used in cancer immunotherapy, while various NOD1/2 inhibitors are being developed to treat chronic inflammatory conditions (DrugBank: DB06744; PubMed: 30104658).

Other names

NOD-like receptorNLRCaspase recruitment domain-containing proteinCARDCARD4CARD15NOD1NOD2NLRC1NLRC2

Agonism of NOD2 (e.g., by mifamurtide) activates macrophages and stimulates the production of pro-inflammatory cytokines for anti-tumor effects; antagonism of NOD1 or NOD2 inhibits the RIPK2-mediated signaling pathway to reduce pathological inflammation in autoimmune diseases.