Nucleotide-binding oligomerization domain-containing protein 1 and 2 (NOD1 and NOD2) (NOD1 and NOD2)

Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) and 2 (NOD2) are two distinct intracellular pattern recognition receptors that function as key sensors of the innate immune system. While they share a similar structural architecture—consisting of a variable N-terminal effector domain, a central nucleotide-binding oligomerization domain, and C-terminal leucine-rich repeats—they recognize different bacterial peptidoglycan fragments (UniProt, 2024). NOD1 detects iE-DAP, primarily from Gram-negative bacteria, whereas NOD2 recognizes MDP, found in both Gram-positive and Gram-negative bacteria (PubMed, 2023). Both receptors signal through the recruitment of the RIPK2 kinase, leading to the activation of NF-κB and MAPK pathways and the subsequent production of pro-inflammatory cytokines (NIH, 2024). Mutations in NOD2 are famously linked to Crohn's disease and Blau syndrome, making these proteins significant targets for both inflammatory disease inhibitors and cancer immunotherapies like mifamurtide (PubChem, 2024; Nature Reviews Drug Discovery, 2022).

Other names

CARD4NLRC1CARD15NLRC2IBD1Caspase recruitment domain-containing protein 4Caspase recruitment domain-containing protein 15

Agonists bind to the leucine-rich repeat (LRR) domain to trigger receptor oligomerization and the recruitment of the adapter kinase RIPK2, which activates NF-κB and MAPK signaling to induce an immune response (PubMed, 2023). Inhibitors target either the nucleotide-binding domain of the NOD proteins or the downstream kinase RIPK2 to prevent the assembly of the nodosome complex, thereby suppressing pathological inflammation (Nature Reviews Drug Discovery, 2022).