nod2 signaling adaptor protein


Summary: A NOD signaling adaptor protein that contains two C-terminal leucine-rich domains which recognize bacterial PEPTIDOGLYCAN. It signals via an N-terminal capase recruitment domain that interacts with other CARD SIGNALING ADAPTOR PROTEINS such as RIP SERINE-THEONINE KINASES. The protein plays a role in the host defense response by signaling the activation of CASPASES and the MAP KINASE SIGNALING SYSTEM. Mutations of the gene encoding the nucleotide oligomerization domain 2 protein have been associated with increased susceptibility to CROHN DISEASE.

Top Publications

  1. Vijayrajratnam S, Pushkaran A, Balakrishnan A, Vasudevan A, Biswas R, Mohan C. Understanding the molecular differential recognition of muramyl peptide ligands by LRR domains of human NOD receptors. Biochem J. 2017;474:2691-2711 pubmed publisher
    ..Thus, our integrated experimental and computational approach elucidates the molecular basis underlying the differential recognition of PG ligands by hNOD receptors. ..
  2. Guagnozzi D, Pagnini C, Delle Fave G, Corleto V. CARD15 and Toll-like receptor 4 mutations in Italian patients with inflammatory bowel disease. Dig Liver Dis. 2012;44:800-1 pubmed publisher
  3. Verway M, Behr M, White J. Vitamin D, NOD2, autophagy and Crohn's disease. Expert Rev Clin Immunol. 2010;6:505-8 pubmed publisher
  4. Balasubramanian I, Gao N. From sensing to shaping microbiota: insights into the role of NOD2 in intestinal homeostasis and progression of Crohn's disease. Am J Physiol Gastrointest Liver Physiol. 2017;313:G7-G13 pubmed publisher
  5. Tschope C, Muller I, Xia Y, Savvatis K, Pappritz K, Pinkert S, et al. NOD2 (Nucleotide-Binding Oligomerization Domain 2) Is a Major Pathogenic Mediator of Coxsackievirus B3-Induced Myocarditis. Circ Heart Fail. 2017;10: pubmed publisher
    ..NOD2 is an important mediator in the viral uptake and inflammatory response during the pathogenesis of CVB3 myocarditis. ..
  6. Ke K, Sul O, Chung S, Suh J, Choi H. Lack of NOD2 attenuates ovariectomy-induced bone loss via inhibition of osteoclasts. J Endocrinol. 2017;235:85-96 pubmed publisher
    ..Our data suggest that NOD2 contributes to bone loss in estrogen deficiency by elevating ROS levels in OCs. ..
  7. Sales Marques C, Cardoso C, Alvarado Arnez L, Illaramendi X, Sales A, Hacker M, et al. Genetic polymorphisms of the IL6 and NOD2 genes are risk factors for inflammatory reactions in leprosy. PLoS Negl Trop Dis. 2017;11:e0005754 pubmed publisher
    ..NOD2 also has a clear functional pro-inflammatory link that is coherent with the exacerbated responses observed in these patients. ..
  8. Kasimsetty S, Shigeoka A, Scheinok A, Gavin A, Ulevitch R, McKay D. Lack of Both Nucleotide-Binding Oligomerization Domain-Containing Proteins 1 and 2 Primes T Cells for Activation-Induced Cell Death. J Immunol. 2017;199:1196-1205 pubmed publisher
  9. Ohlsson C, Nigro G, Boneca I, Backhed F, Sansonetti P, Sjögren K. Regulation of bone mass by the gut microbiota is dependent on NOD1 and NOD2 signaling. Cell Immunol. 2017;317:55-58 pubmed publisher

More Information


  1. Saxena A, Lopes F, Poon K, McKay D. Absence of the NOD2 protein renders epithelia more susceptible to barrier dysfunction due to mitochondrial dysfunction. Am J Physiol Gastrointest Liver Physiol. 2017;313:G26-G38 pubmed publisher
    ..Thus a significant barrier defect occurs with NOD2 deficiency in conjunction with metabolic stress that could contribute to inflammation. ..
  2. Williams H, Crompton R, Thomason H, Campbell L, Singh G, McBain A, et al. Cutaneous Nod2 Expression Regulates the Skin Microbiome and Wound Healing in a Murine Model. J Invest Dermatol. 2017;137:2427-2436 pubmed publisher
    ..Collectively, these studies show the importance of the microbial communities in skin wound healing outcome. ..
  3. Fekete T, Koncz G, Szabo B, Gregus A, Rajnavölgyi E. Interferon gamma boosts the nucleotide oligomerization domain 2-mediated signaling pathway in human dendritic cells in an X-linked inhibitor of apoptosis protein and mammalian target of rapamycin-dependent manner. Cell Mol Immunol. 2017;14:380-391 pubmed publisher
    ..Our results demonstrate, for the first time, that IFNγ positively affects NOD2-mediated signaling in human cDCs, in a manner considerably dependent on XIAP and partially dependent on mTOR. ..
  4. Kugelberg E. Pattern recognition receptors: curbing gut inflammation. Nat Rev Immunol. 2014;14:583 pubmed publisher
  5. Sudo T, Okada Y, Ozaki K, Urayama K, Kanai M, Kobayashi H, et al. Association of NOD2 Mutations with Aggressive Periodontitis. J Dent Res. 2017;96:1100-1105 pubmed publisher
    ..These results demonstrated NOD2 as a novel gene involved in AgP. ..
  6. Ikeda K, Kambe N, Takei S, Nakano T, Inoue Y, Tomiita M, et al. Ultrasonographic assessment reveals detailed distribution of synovial inflammation in Blau syndrome. Arthritis Res Ther. 2014;16:R89 pubmed publisher
    ..Our data also demonstrate that ultrasonography can be a potent tool in monitoring the activity of synovial inflammation and in investigating the pathophysiology of arthritis in this rare but archetypical autoinflammatory condition. ..
  7. Van Limbergen J, Geddes K, Henderson P, Russell R, Drummond H, Satsangi J, et al. Paneth cell marker CD24 in NOD2 knockout organoids and in inflammatory bowel disease (IBD). Gut. 2015;64:353-4 pubmed publisher
  8. Tamzaourte M, Errabih I, Krami H, Maha F, Maria L, Benzzoubeir N, et al. [NOD2 gene mutation in Moroccan patients with Crohn's disease: prevalence, genotypic study and correlation of NOD2 gene mutation with the phenotype of Crohn's disease]. Pan Afr Med J. 2017;27:116 pubmed publisher
    ..The prevalence of NOD2/ CARD15 mutation in our case series is low. This mutation is correlated with severe Crohn's disease. ..
  9. Aaby P, Benn C. Saving lives by training innate immunity with bacille Calmette-Guerin vaccine. Proc Natl Acad Sci U S A. 2012;109:17317-8 pubmed publisher
  10. Daley D, Mani V, Mohan N, Akkad N, Pandian G, Savadkar S, et al. NLRP3 signaling drives macrophage-induced adaptive immune suppression in pancreatic carcinoma. J Exp Med. 2017;214:1711-1724 pubmed publisher
    ..Similarly, transfer of PDA-entrained macrophages or T cells from NLRP3-/- hosts was protective. These data suggest that targeting NLRP3 holds the promise for the immunotherapy of PDA. ..
  11. Wong K. The Role of ESX-1 in Mycobacterium tuberculosis Pathogenesis. Microbiol Spectr. 2017;5: pubmed publisher
    ..Inhibitors that block the ESX-1 system or block host factors critical for ESX-1 toxicity have been identified and should represent attractive potential new antituberculosis drugs. ..
  12. Wang S, Yang J, Li X, Liu Z, Wu Y, Si G, et al. Discovery of 1,4-Benzodiazepine-2,5-dione (BZD) Derivatives as Dual Nucleotide Binding Oligomerization Domain Containing 1/2 (NOD1/NOD2) Antagonists Sensitizing Paclitaxel (PTX) To Suppress Lewis Lung Carcinoma (LLC) Growth in Vivo. J Med Chem. 2017;60:5162-5192 pubmed publisher
    ..This study establishes the possibility for using adjuvant treatment to combat cancer by antagonizing both NOD1 and NOD2 signaling. ..
  13. Park O, Kim J, Yang J, Yun C, Han S. Muramyl Dipeptide, a Shared Structural Motif of Peptidoglycans, Is a Novel Inducer of Bone Formation through Induction of Runx2. J Bone Miner Res. 2017;32:1455-1468 pubmed publisher
    ..In conclusion, we suggest that MDP is a novel inducer of bone formation that could potentially be a new therapeutic molecule to protect against osteoporosis. © 2017 American Society for Bone and Mineral Research. ..
  14. Yang B, Lyu H, Sun D, Wang J, Wu R. [Staphylococcus aureus promotes NOD2 expression in bovine mammary epithelial cells]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2017;33:741-745 pubmed
    ..Levels of NOD2 mRNA and protein expression were not significantly upregulated by the stimulation with heat-inactivated S. aureus. Conclusion S. aureus infection could induce the up-regulation of NOD2 expression in BMECs. ..
  15. Holden J, O Brien Simpson N, Lenzo J, Orth R, Mansell A, Reynolds E. Porphyromonas gulae Activates Unprimed and Gamma Interferon-Primed Macrophages via the Pattern Recognition Receptors Toll-Like Receptor 2 (TLR2), TLR4, and NOD2. Infect Immun. 2017;85: pubmed publisher
    ..In conclusion, P. gulae induces a strong TLR2-dependent inflammatory M1 macrophage response which may be important in establishing the chronic inflammation associated with periodontal disease in companion animals. ..
  16. Schaefer A, Wastyk H, Mohanan V, Hou C, Lauro M, Melnyk J, et al. Crohn's Disease Variants of Nod2 Are Stabilized by the Critical Contact Region of Hsp70. Biochemistry. 2017;56:4445-4448 pubmed publisher
    ..This work suggests that CD-associated Nod2 variants could be stabilized in vivo with a molecular chaperone. ..