NOD2

Nucleotide-binding oligomerization domain containing 2

Identifiers

NOD2 ; ACUG; BLAU; CARD15; CD; CLR16.3; IBD1; NLRC2; NOD2B; PSORAS1

External IDs

OMIM: 605956 MGI: 2429397 HomoloGene: 11156 ChEMBL: 1293266 GeneCards: NOD2 Gene

Gene ontology
Molecular function	• actin binding • protein binding • ATP binding • enzyme binding • protein kinase binding • Hsp70 protein binding • muramyl dipeptide binding • peptidoglycan binding • CARD domain binding • Hsp90 protein binding
Cellular component	• cytoplasm • cytosol • cytoskeleton • plasma membrane • COP9 signalosome • cell surface • basolateral plasma membrane • vesicle • protein complex
Biological process	• activation of MAPK activity • toll-like receptor signaling pathway • innate immune response in mucosa • cytokine production involved in immune response • cytokine secretion involved in immune response • immunoglobulin production involved in immunoglobulin mediated immune response • positive regulation of dendritic cell antigen processing and presentation • negative regulation of T cell mediated immunity • MyD88-dependent toll-like receptor signaling pathway • MyD88-independent toll-like receptor signaling pathway • positive regulation of type 2 immune response • negative regulation of inflammatory response to antigenic stimulus • positive regulation of humoral immune response mediated by circulating immunoglobulin • defense response • positive regulation of biosynthetic process of antibacterial peptides active against Gram-positive bacteria • JNK cascade • detection of biotic stimulus • detection of bacterium • maintenance of gastrointestinal epithelium • negative regulation of NF-kappaB transcription factor activity • response to muramyl dipeptide • response to lipopolysaccharide • detection of muramyl dipeptide • negative regulation of interferon-gamma production • negative regulation of interleukin-12 production • negative regulation of interleukin-18 production • negative regulation of interleukin-2 production • negative regulation of tumor necrosis factor production • positive regulation of interleukin-1 beta production • positive regulation of interleukin-10 production • positive regulation of interleukin-12 production • positive regulation of interleukin-17 production • positive regulation of interleukin-6 production • positive regulation of interleukin-8 production • positive regulation of tumor necrosis factor production • positive regulation of stress-activated MAPK cascade • toll-like receptor 2 signaling pathway • negative regulation of toll-like receptor 2 signaling pathway • toll-like receptor 3 signaling pathway • toll-like receptor 4 signaling pathway • toll-like receptor 5 signaling pathway • toll-like receptor 9 signaling pathway • toll-like receptor 10 signaling pathway • activation of MAPK activity involved in innate immune response • intracellular signal transduction • TRIF-dependent toll-like receptor signaling pathway • nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway • toll-like receptor TLR1:TLR2 signaling pathway • toll-like receptor TLR6:TLR2 signaling pathway • defense response to bacterium • positive regulation of I-kappaB kinase/NF-kappaB signaling • response to exogenous dsRNA • positive regulation of phosphatidylinositol 3-kinase activity • negative regulation of growth of symbiont in host • innate immune response • positive regulation of Notch signaling pathway • positive regulation of transcription from RNA polymerase II promoter • positive regulation of JNK cascade • positive regulation of gamma-delta T cell activation • positive regulation of epithelial cell proliferation • positive regulation of interleukin-1 beta secretion • regulation of inflammatory response • positive regulation of peptidyl-tyrosine phosphorylation • positive regulation of phagocytosis • defense response to Gram-positive bacterium • positive regulation of B cell activation • positive regulation of NF-kappaB transcription factor activity • protein oligomerization • positive regulation of oxidoreductase activity • stress-activated MAPK cascade • positive regulation of nitric-oxide synthase biosynthetic process • positive regulation of prostaglandin-endoperoxide synthase activity • positive regulation of ERK1 and ERK2 cascade • nucleotide-binding oligomerization domain containing signaling pathway • nucleotide-binding oligomerization domain containing 2 signaling pathway • cellular response to peptidoglycan • cellular response to muramyl dipeptide • macrophage inflammatory protein-1 alpha production • regulation of neutrophil chemotaxis • positive regulation of cytokine production involved in inflammatory response • positive regulation of NIK/NF-kappaB signaling • negative regulation of macrophage apoptotic process • positive regulation of prostaglandin-E synthase activity
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 16:
50.69 – 50.73 Mb

Chr 8:
88.65 – 88.69 Mb

PubMed search

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.

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.^[3]

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^[4]

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.^[5]

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.^[6]

Clinical significance

Mutations in this gene have been associated with Crohn's disease,^[4] Blau syndrome, severe pulmonary sarcoidosis ^[7] and Graft-versus-host disease.^[8]

The NOD2 gene is linked to inflammatory diseases such as Inflammatory bowel disease/Crohn's Disease and Blau syndrome.^[9]^[10]

Interactions

NOD2 has been shown to interact with NLRC4.^[11]^[12]

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.^[13]

References

↑ Gilberts EC, Greenstein AJ, Katsel P, Harpaz N, Greenstein RJ (Dec 1994). "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. doi:10.1073/pnas.91.26.12721. PMC 45511. PMID 7809109.
↑ Hugot JP, Laurent-Puig P, Gower-Rousseau C, Olson JM, Lee JC, Beaugerie L, Naom I, Dupas JL, Van Gossum A, Orholm M, Bonaiti-Pellie C, Weissenbach J, Mathew CG, Lennard-Jones JE, Cortot A, Colombel JF, Thomas G (Feb 1996). "Mapping of a susceptibility locus for Crohn's disease on chromosome 16". Nature 379 (6568): 821–3. doi:10.1038/379821a0. PMID 8587604.
↑ Kufer TA, Banks DJ, Philpott DJ (Aug 2006). "Innate immune sensing of microbes by Nod proteins". Annals of the New York Academy of Sciences 1072: 19–27. doi:10.1196/annals.1326.020. PMID 17057187.
1 2 Nakagome S, Mano S, Kozlowski L, Bujnicki JM, Shibata H, Fukumaki Y, Kidd JR, Kidd KK, Kawamura S, Oota H (Jun 2012). "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. doi:10.1093/molbev/mss006. PMC 3697811. PMID 22319155.
↑ Ogura Y, Inohara N, Benito A, Chen FF, Yamaoka S, Nunez G (Feb 2001). "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. doi:10.1074/jbc.M008072200. PMID 11087742.
↑ "Entrez Gene: NOD2 nucleotide-binding oligomerization domain containing 2".
↑ Sato H, Williams HR, Spagnolo P, Abdallah A, Ahmad T, Orchard TR, Copley SJ, Desai SR, Wells AU, du Bois RM, Welsh KI (Feb 2010). "CARD15/NOD2 polymorphisms are associated with severe pulmonary sarcoidosis.". Eur Respir J 35 (2): 324–30. doi:10.1183/09031936.00010209. PMID 19679608.
↑ Zhao H, Jia M, Wang Z, Cheng Y, Luo Z, Chen Y, Xu X, Yang S, Tang Y (Jun 2015). "Association between NOD2 single nucleotide polymorphisms and Grade III-IV acute graft-versus-host disease: A meta-analysis". Hematology 20 (5): 254–62. doi:10.1179/1607845414Y.0000000202. PMID 25248089.
↑ Radford-Smith G, Pandeya N (Nov 2006). "Associations between NOD2/CARD15 genotype and phenotype in Crohn's disease--Are we there yet?". World Journal of Gastroenterology 12 (44): 7097–103. PMID 17131470.
↑ Kim TH, Payne U, Zhang X, Iwanaga Y, Davey MP, Rosenbaum JT, Inman RD (Jan 2007). "Altered host:pathogen interactions conferred by the Blau syndrome mutation of NOD2". Rheumatology International 27 (3): 257–62. doi:10.1007/s00296-006-0250-0. PMID 17096091.
↑ Damiano JS, Oliveira V, Welsh K, Reed JC (Jul 2004). "Heterotypic interactions among NACHT domains: implications for regulation of innate immune responses". The Biochemical Journal 381 (Pt 1): 213–9. doi:10.1042/BJ20031506. PMC 1133779. PMID 15107016.
↑ Damiano JS, Stehlik C, Pio F, Godzik A, Reed JC (Jul 2001). "CLAN, a novel human CED-4-like gene". Genomics 75 (1-3): 77–83. doi:10.1006/geno.2001.6579. PMID 11472070.
↑ Sabbah A, Chang TH, Harnack R, Frohlich V, Tominaga K, Dube PH, Xiang Y, Bose S (Oct 2009). "Activation of innate immune antiviral responses by Nod2". Nature Immunology 10 (10): 1073–80. doi:10.1038/ni.1782. PMC 2752345. PMID 19701189.

Punchard NA (Oct 2001). "Overview: Nod2, cause of, or contributor to, Crohn's disease". Current Opinion in Investigational Drugs 2 (10): 1378–81. PMID 11890351.
Satsangi J, Morecroft J, Shah NB, Nimmo E (Feb 2003). "Genetics of inflammatory bowel disease: scientific and clinical implications". Best Practice & Research. Clinical Gastroenterology 17 (1): 3–18. doi:10.1053/bega.2002.0349. PMID 12617879.
Rosenbaum JT, Planck SR, Davey MP, Iwanaga Y, Kurz DE, Martin TM (Oct 2003). "With a mere nod, uveitis enters a new era". American Journal of Ophthalmology 136 (4): 729–32. doi:10.1016/S0002-9394(03)00569-5. PMID 14516815.
Kurokawa T, Kikuchi T, Ohta K, Imai H, Yoshimura N (Oct 2003). "Ocular manifestations in Blau syndrome associated with a CARD15/Nod2 mutation". Ophthalmology 110 (10): 2040–4. doi:10.1016/S0161-6420(03)00717-6. PMID 14522785.
Girardin SE, Hugot JP, Sansonetti PJ (Dec 2003). "Lessons from Nod2 studies: towards a link between Crohn's disease and bacterial sensing". Trends in Immunology 24 (12): 652–8. doi:10.1016/j.it.2003.10.007. PMID 14644139.
Newman B, Siminovitch K (Dec 2003). "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 (2003). "IBD and genetics: new developments". Scandinavian Journal of Gastroenterology. Supplement 38 (239): 63–8. doi:10.1080/00855920310002717. PMID 14743885.
Kambe N, Nishikomori R, Kanazawa N (Aug 2005). "The cytosolic pattern-recognition receptor Nod2 and inflammatory granulomatous disorders". Journal of Dermatological Science 39 (2): 71–80. doi:10.1016/j.jdermsci.2005.04.001. PMID 15927452.
Newman B, Siminovitch KA (Jul 2005). "Recent advances in the genetics of inflammatory bowel disease". Current Opinion in Gastroenterology 21 (4): 401–7. PMID 15930978.
Martinon F, Tschopp J (Aug 2005). "NLRs join TLRs as innate sensors of pathogens". Trends in Immunology 26 (8): 447–54. doi:10.1016/j.it.2005.06.004. PMID 15967716.
Strober W, Murray PJ, Kitani A, Watanabe T (Jan 2006). "Signalling pathways and molecular interactions of NOD1 and NOD2". Nature Reviews. Immunology 6 (1): 9–20. doi:10.1038/nri1747. PMID 16493424.
Cavanaugh J (Jun 2006). "NOD2: ethnic and geographic differences". World Journal of Gastroenterology 12 (23): 3673–7. PMID 16773683.
Hugot JP (Aug 2006). "CARD15/NOD2 mutations in Crohn's disease". Annals of the New York Academy of Sciences 1072 (1): 9–18. doi:10.1196/annals.1326.011. PMID 17057186.
Vignal C, Singer E, Peyrin-Biroulet L, Desreumaux P, Chamaillard M (Apr 2007). "How NOD2 mutations predispose to Crohn's disease?". Microbes and Infection / Institut Pasteur 9 (5): 658–63. doi:10.1016/j.micinf.2007.01.016. PMID 17379562.
Quaglietta L, te Velde A, Staiano A, Troncone R, Hommes DW (May 2007). "Functional consequences of NOD2/CARD15 mutations in Crohn disease". Journal of Pediatric Gastroenterology and Nutrition 44 (5): 529–39. doi:10.1097/MPG.0b013e31803815ee. PMID 17460484.
van der Linde K, Boor PP, Houwing-Duistermaat JJ, Crusius BJ, Wilson PJ, Kuipers EJ, de Rooij FW (Jun 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:10.1097/01.meg.0000236887.44214.6a. PMID 17489054.

NOD-like receptor family

CARD domain containing	NOD1/NLRC1 NOD2/NLRC2 NLRC3 NLRC4 NLRC5

Pyrin domain containing	NLRP1 NLRP2 NLRP3 NLRP4 NLRP5 NLRP6 NLRP7 NLRP8 NLRP9 NLRP10 NLRP11 NLRP12 NLRP13 NLRP14

Apoptosis inhibitory protein	NAIP

Family member X1	NLRX1

This article is issued from Wikipedia - version of the Wednesday, January 20, 2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.