Biology:NOD2

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A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Nucleotide-binding oligomerization domain-containing protein 2 (NOD2), also known as caspase recruitment domain-containing protein 15 (CARD15) or inflammatory bowel disease protein 1 (IBD1), is a protein that in humans is encoded by the NOD2 gene located on chromosome 16.[1][2] NOD2 plays an important role in the immune system. It recognizes bacterial molecules (peptidoglycans) and stimulates an immune reaction [3].

NOD2 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.[4]

Structure

NOD2 protein model consisting two N-terminal CARD domains (red) connected via helical linker (blue) with central NOD domain (green). At C-terminus LRR domain (cyan) is located[5]

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 domain involved in protein self-oligomerization. The N-terminal portion contains two CARD domains known to play a role in apoptosis and NF-κB activation pathways.[6]

Function

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.[7]

Clinical significance

Mutations in this gene have been associated with Crohn's disease,[5] Blau syndrome, severe pulmonary sarcoidosis [8] and Graft-versus-host disease.[9]

The NOD2 gene is linked to inflammatory diseases such as Inflammatory bowel disease/Crohn's disease and Blau syndrome.[10][11]

Interactions

NOD2 has been shown to interact with NLRC4.[12][13]

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.[14]

See also

References

  1. ↑ "Molecular evidence for two forms of Crohn disease". Proceedings of the National Academy of Sciences of the United States of America 91 (26): 12721–4. Dec 1994. doi:10.1073/pnas.91.26.12721. PMID 7809109. 
  2. ↑ "Mapping of a susceptibility locus for Crohn's disease on chromosome 16". Nature 379 (6568): 821–3. Feb 1996. doi:10.1038/379821a0. PMID 8587604. 
  3. ↑ "Sweeten PAMPs: Role of Sugar Complexed PAMPs in Innate Immunity and Vaccine Biology". Frontiers in Immunology 4: 248. September 2013. doi:10.3389/fimmu.2013.00248. PMID 24032031. 
  4. ↑ "Innate immune sensing of microbes by Nod proteins". Annals of the New York Academy of Sciences 1072: 19–27. Aug 2006. doi:10.1196/annals.1326.020. PMID 17057187. 
  5. ↑ 5.0 5.1 "Crohn's disease risk alleles on the NOD2 locus have been maintained by natural selection on standing variation". Molecular Biology and Evolution 29 (6): 1569–85. Jun 2012. doi:10.1093/molbev/mss006. PMID 22319155. 
  6. ↑ "Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-kappaB". The Journal of Biological Chemistry 276 (7): 4812–8. Feb 2001. doi:10.1074/jbc.M008072200. PMID 11087742. 
  7. ↑ "Entrez Gene: NOD2 nucleotide-binding oligomerization domain containing 2". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=64127. 
  8. ↑ "CARD15/NOD2 polymorphisms are associated with severe pulmonary sarcoidosis.". Eur Respir J 35 (2): 324–30. Feb 2010. doi:10.1183/09031936.00010209. PMID 19679608. 
  9. ↑ "Association between NOD2 single nucleotide polymorphisms and Grade III-IV acute graft-versus-host disease: A meta-analysis". Hematology 20 (5): 254–62. Jun 2015. doi:10.1179/1607845414Y.0000000202. PMID 25248089. 
  10. ↑ "Associations between NOD2/CARD15 genotype and phenotype in Crohn's disease--Are we there yet?". World Journal of Gastroenterology 12 (44): 7097–103. Nov 2006. doi:10.3748/wjg.v12.i44.7097. PMID 17131470. 
  11. ↑ "Altered host:pathogen interactions conferred by the Blau syndrome mutation of NOD2". Rheumatology International 27 (3): 257–62. Jan 2007. doi:10.1007/s00296-006-0250-0. PMID 17096091. 
  12. ↑ "Heterotypic interactions among NACHT domains: implications for regulation of innate immune responses". The Biochemical Journal 381 (Pt 1): 213–9. Jul 2004. doi:10.1042/BJ20031506. PMID 15107016. 
  13. ↑ "CLAN, a novel human CED-4-like gene". Genomics 75 (1-3): 77–83. Jul 2001. doi:10.1006/geno.2001.6579. PMID 11472070. 
  14. ↑ "Activation of innate immune antiviral responses by Nod2". Nature Immunology 10 (10): 1073–80. Oct 2009. doi:10.1038/ni.1782. PMID 19701189. 

Further reading

  • "Overview: Nod2, cause of, or contributor to, Crohn's disease". Current Opinion in Investigational Drugs 2 (10): 1378–81. Oct 2001. PMID 11890351. 
  • "Genetics of inflammatory bowel disease: scientific and clinical implications". Best Practice & Research. Clinical Gastroenterology 17 (1): 3–18. Feb 2003. doi:10.1053/bega.2002.0349. PMID 12617879. 
  • "With a mere nod, uveitis enters a new era". American Journal of Ophthalmology 136 (4): 729–32. Oct 2003. doi:10.1016/S0002-9394(03)00569-5. PMID 14516815. 
  • "Ocular manifestations in Blau syndrome associated with a CARD15/Nod2 mutation". Ophthalmology 110 (10): 2040–4. Oct 2003. doi:10.1016/S0161-6420(03)00717-6. PMID 14522785. 
  • "Lessons from Nod2 studies: towards a link between Crohn's disease and bacterial sensing". Trends in Immunology 24 (12): 652–8. Dec 2003. doi:10.1016/j.it.2003.10.007. PMID 14644139. 
  • "Inflammatory bowel disease: Crohn's disease and the success of NODern genetics". Clinical and Investigative Medicine. Médecine Clinique Et Experimentale 26 (6): 303–14. Dec 2003. PMID 14690304. 
  • "IBD and genetics: new developments". Scandinavian Journal of Gastroenterology. Supplement 38 (239): 63–8. 2003. doi:10.1080/00855920310002717. PMID 14743885. 
  • "The cytosolic pattern-recognition receptor Nod2 and inflammatory granulomatous disorders". Journal of Dermatological Science 39 (2): 71–80. Aug 2005. doi:10.1016/j.jdermsci.2005.04.001. PMID 15927452. 
  • "Recent advances in the genetics of inflammatory bowel disease". Current Opinion in Gastroenterology 21 (4): 401–7. Jul 2005. PMID 15930978. 
  • "NLRs join TLRs as innate sensors of pathogens". Trends in Immunology 26 (8): 447–54. Aug 2005. doi:10.1016/j.it.2005.06.004. PMID 15967716. 
  • "Signalling pathways and molecular interactions of NOD1 and NOD2". Nature Reviews. Immunology 6 (1): 9–20. Jan 2006. doi:10.1038/nri1747. PMID 16493424. 
  • "NOD2: ethnic and geographic differences". World Journal of Gastroenterology 12 (23): 3673–7. Jun 2006. doi:10.3748/wjg.v12.i23.3673. PMID 16773683. 
  • "CARD15/NOD2 mutations in Crohn's disease". Annals of the New York Academy of Sciences 1072 (1): 9–18. Aug 2006. doi:10.1196/annals.1326.011. PMID 17057186. 
  • "How NOD2 mutations predispose to Crohn's disease?". Microbes and Infection / Institut Pasteur 9 (5): 658–63. Apr 2007. doi:10.1016/j.micinf.2007.01.016. PMID 17379562. 
  • "Functional consequences of NOD2/CARD15 mutations in Crohn disease". Journal of Pediatric Gastroenterology and Nutrition 44 (5): 529–39. May 2007. doi:10.1097/MPG.0b013e31803815ee. PMID 17460484. 
  • "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. Jun 2007. doi:10.1097/01.meg.0000236887.44214.6a. PMID 17489054. 





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