Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) (NOD2)

Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is a key intracellular pattern recognition receptor that detects muramyl dipeptide (MDP), a component of bacterial cell walls (UniProt, 2024). It is highly expressed in the intestinal crypt, particularly in Paneth cells and enterocytes, where it regulates the secretion of antimicrobial peptides and maintains the integrity of the mucosal barrier (Philpott et al., 2014). NOD2 signaling is essential for gut homeostasis, as it coordinates the innate immune response to the intestinal microbiota (PubMed, PMID: 21844392). Genetic polymorphisms in NOD2 are the strongest known genetic risk factors for Crohn's disease, leading to defective bacterial clearance and subsequent chronic inflammation (Hugot et al., 2001). Beyond the gut, NOD2 is involved in systemic inflammatory conditions like Blau syndrome (NIH, 2023). Current therapeutic research focuses on both NOD2 agonists to boost immunity and antagonists to curb pathological inflammation (PubChem, 2024). In the intestinal crypt, NOD2 also plays a role in supporting the survival of intestinal stem cells during stress, highlighting its importance in epithelial regeneration (PubMed, PMID: 21844392).

Other names

Caspase recruitment domain-containing protein 15CARD15IBD1NLRC2Nucleotide-binding oligomerization domain protein 2

NOD2 acts as an intracellular sensor for muramyl dipeptide (MDP), a conserved motif in bacterial peptidoglycan. Upon ligand binding, NOD2 undergoes oligomerization and recruits the kinase RIPK2 via CARD-CARD interactions, which subsequently activates the NF-kappaB and MAPK signaling pathways to induce the expression of pro-inflammatory and antimicrobial genes (UniProt, 2024; PubMed, PMID: 18425105).