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NOD2 (nucleotide-binding oligomerization domain containing 2) is a protein, also known as the caspase recruitment domain family, member 15 (CARD15), which plays an important role in the immune system. It is an intracellular pattern recognition receptor, which is similar in structure to resistant proteins of plants and recognizes molecules containing the specific structure called muramyl dipeptide (MDP) that is found in certain bacteria.[1]
The C-terminal portion of the protein contains a leucine-rich repeat domain that is known to play a role in protein-protein interactions. The middle part of the protein is characterized by a NOD involved in protein self-oligomerization. The N-terminal portion contains two CARDs known to play a role in apoptosis and NF-kappa B activation pathways.[2]
The NOD2 gene is linked to inflammatory diseases such as inflammatory bowel disease/Crohn's Disease and Blau syndrome.[3][4] It is located on chromosome 16 in humans.
This gene is a member of the Nod1/Apaf-1 family (also known as Nod-like receptor family) and encodes a protein with two caspase recruitment domains (CARDs) and eleven leucine-rich repeats (LRRs). The protein is primarily expressed in the peripheral blood leukocytes. It plays a role in the immune response by recognizing the bacterial molecules which possess the muramyl dipeptide (MDP) moiety and activating the NF-κB protein. Mutations in this gene have been associated with Crohn's disease, Blau syndrome.[5] and graft-versus-host disease.
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Interactions
NOD2 has been shown to interact with NLRC4.[6][7]
NOD2 has also been shown to bind to MAVS in response to ssRNA or viral RNA treatment and activate the IFN response. This is the first report of NOD2 acting as a pattern-recognition receptor for viruses.[8]
See also
- Mifamurtide, a NOD2 activator for the treatment of osteosarcoma
References
- ^ Kufer T, Banks D, Philpott D (2006). "Innate immune sensing of microbes by Nod proteins". Ann. N. Y. Acad. Sci. 1072: 19–27. doi:. PMID 17057187.
- ^ Ogura Y, Inohara N, Benito A et al. (2001). "Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF kappaB". Biol Chem 276: 4812–8.
- ^ Radford-Smith G, Pandeya N (2006). "Associations between NOD2/CARD15 genotype and phenotype in Crohn's disease--Are we there yet?". World J. Gastroenterol. 12 (44): 7097–103. PMID 17131470.
- ^ Kim T, Payne U, Zhang X, Iwanaga Y, Davey M, Rosenbaum J, Inman R (2007). "Altered host:pathogen interactions conferred by the Blau syndrome mutation of NOD2". Rheumatol. Int. 27 (3): 257–62. doi:. PMID 17096091.
- ^ "Entrez Gene: NOD2 nucleotide-binding oligomerization domain containing 2". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=64127.
- ^ Damiano, Jason S; Oliveira Vasco, Welsh Kate, Reed John C (Jul. 2004). "Heterotypic interactions among NACHT domains: implications for regulation of innate immune responses". Biochem. J. (England) 381 (Pt 1): 213–9. doi:. PMID 15107016.
- ^ Damiano, J S; Stehlik C, Pio F, Godzik A, Reed J C (Jul. 2001). "CLAN, a novel human CED-4-like gene". Genomics (United States) 75 (1-3): 77–83. doi:. ISSN 0888-7543. PMID 11472070.
- ^ Sabbah A, Chang TH, Harnack R, Frohlich V, Tominaga K, Dube PH, Xiang Y, Bose S (August 2009). "Activation of innate immune antiviral responses by Nod2". Nat. Immunol.. doi:. PMID 19701189.
Further reading
- Punchard NA (2002). "Overview: Nod2, cause of, or contributor to, Crohn's disease.". Current opinion in investigational drugs (London, England : 2000) 2 (10): 1378–81. PMID 11890351.
- Satsangi J, Morecroft J, Shah NB, Nimmo E (2003). "Genetics of inflammatory bowel disease: scientific and clinical implications.". Best practice & research. Clinical gastroenterology 17 (1): 3–18. doi:. PMID 12617879.
- Rosenbaum JT, Planck SR, Davey MP, et al. (2003). "With a mere nod, uveitis enters a new era.". Am. J. Ophthalmol. 136 (4): 729–32. doi:. PMID 14516815.
- Kurokawa T, Kikuchi T, Ohta K, et al. (2003). "Ocular manifestations in Blau syndrome associated with a CARD15/Nod2 mutation.". Ophthalmology 110 (10): 2040–4. doi:. PMID 14522785.
- Girardin SE, Hugot JP, Sansonetti PJ (2004). "Lessons from Nod2 studies: towards a link between Crohn's disease and bacterial sensing.". Trends Immunol. 24 (12): 652–8. doi:. PMID 14644139.
- Newman B, Siminovitch K (2004). "Inflammatory bowel disease: Crohn's disease and the success of NODern genetics.". Clinical and investigative medicine. Médecine clinique et experimentale 26 (6): 303–14. PMID 14690304.
- Oostenbrug LE, van Dullemen HM, te Meerman GJ, Jansen PL (2004). "IBD and genetics: new developments.". Scand. J. Gastroenterol. Suppl. (239): 63–8. PMID 14743885.
- Kambe N, Nishikomori R, Kanazawa N (2005). "The cytosolic pattern-recognition receptor Nod2 and inflammatory granulomatous disorders.". J. Dermatol. Sci. 39 (2): 71–80. doi:. PMID 15927452.
- Newman B, Siminovitch KA (2005). "Recent advances in the genetics of inflammatory bowel disease.". Curr. Opin. Gastroenterol. 21 (4): 401–7. PMID 15930978.
- Martinon F, Tschopp J (2006). "NLRs join TLRs as innate sensors of pathogens.". Trends Immunol. 26 (8): 447–54. doi:. PMID 15967716.
- Strober W, Murray PJ, Kitani A, Watanabe T (2006). "Signalling pathways and molecular interactions of NOD1 and NOD2.". Nat. Rev. Immunol. 6 (1): 9–20. doi:. PMID 16493424.
- Cavanaugh J (2006). "NOD2: ethnic and geographic differences.". World J. Gastroenterol. 12 (23): 3673–7. PMID 16773683.
- Hugot JP (2006). "CARD15/NOD2 mutations in Crohn's disease.". Ann. N. Y. Acad. Sci. 1072: 9–18. doi:. PMID 17057186.
- Vignal C, Singer E, Peyrin-Biroulet L, et al. (2007). "How NOD2 mutations predispose to Crohn's disease?". Microbes Infect. 9 (5): 658–63. doi:. PMID 17379562.
- Quaglietta L, te Velde A, Staiano A, et al. (2007). "Functional consequences of NOD2/CARD15 mutations in Crohn disease.". J. Pediatr. Gastroenterol. Nutr. 44 (5): 529–39. doi:. PMID 17460484.
- van der Linde K, Boor PP, Houwing-Duistermaat JJ, et al. (2007). "CARD15 mutations in Dutch familial and sporadic inflammatory bowel disease and an overview of European studies.". European journal of gastroenterology & hepatology 19 (6): 449–59. doi:. PMID 17489054.
External links
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