Nucleotide-binding oligomerization domain-containing protein 1 (NOD1)

Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is an intracellular pattern recognition receptor primarily involved in the innate immune response[1][2][4][6]. It recognizes a specific structural motif, γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP), found in bacterial peptidoglycan, particularly from Gram-negative and some Gram-positive bacteria[1][5]. Upon binding its ligand, NOD1 oligomerizes and recruits the kinase RIPK2 via its caspase recruitment domain (CARD), activating signaling pathways such as NF-κB and MAPK and leading to the production of inflammatory cytokines and antimicrobial responses[2][4][6]. It also contributes to autophagy and can induce apoptosis. NOD1 is ubiquitously expressed and plays a central regulatory role in host defense, immune homeostasis (especially in the gut), and diseases linked to inflammation, infection, allergic disease, and metabolic disorders like insulin resistance[3][4][5][6]. Genetic variation in NOD1 is associated with disease susceptibility, making it a potential therapeutic target[5][7].

Other names

CARD4NLRC1CLR7.1Caspase recruitment domain family, member 4NLR family, CARD domain containing 1Nucleotide-binding oligomerization domain, leucine-rich repeat and CARD domain containing 1

Inhibition of NOD1 blocks downstream NF-κB and MAPK activation, reducing inflammatory cytokine production; Activation by ligands (such as iE-DAP) promotes receptor oligomerization, recruitment of RIPK2, and subsequent signaling leading to inflammation