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{{Infobox_gene}}
{{PBB_Controls
'''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 (human)|chromosome 16]].<ref name="pmid7809109">{{cite journal | vauthors = Gilberts EC, Greenstein AJ, Katsel P, Harpaz N, Greenstein RJ | title = Molecular evidence for two forms of Crohn disease | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 91 | issue = 26 | pages = 12721–4 | date = Dec 1994 | pmid = 7809109 | pmc = 45511 | doi = 10.1073/pnas.91.26.12721 }}</ref><ref name="pmid8587604">{{cite journal | vauthors = 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 | title = Mapping of a susceptibility locus for Crohn's disease on chromosome 16 | journal = Nature | volume = 379 | issue = 6568 | pages = 821–3 | date = Feb 1996 | pmid = 8587604 | doi = 10.1038/379821a0 }}</ref> NOD2 plays an important role in the [[immune system]]. It recognizes bacterial molecules ([[peptidoglycans]]) and stimulates an immune reaction.
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
NOD2 is an intracellular [[pattern recognition receptor]], which is similar in structure to [[resistant protein]]s of plants and recognizes molecules containing the specific structure called [[muramyl dipeptide]] (MDP) that is found in certain [[bacteria]].<ref name="pmid17057187">{{cite journal | vauthors = Kufer TA, Banks DJ, Philpott DJ | title = Innate immune sensing of microbes by Nod proteins | journal = Annals of the New York Academy of Sciences | volume = 1072 | issue =  | pages = 19–27 | date = Aug 2006 | pmid = 17057187 | doi = 10.1196/annals.1326.020 }}</ref>
{{GNF_Protein_box
| image = 
| image_source = 
| PDB =
| Name = Nucleotide-binding oligomerization domain containing 2
| HGNCid = 5331
| Symbol = NOD2
| AltSymbols =; CD; ACUG; BLAU; CARD15; CLR16.3; IBD1; NLRC2; NOD2B; PSORAS1
| OMIM = 605956
| ECnumber = 
| Homologene = 11156
| MGIid = 2429397
| GeneAtlas_image1 = PBB_GE_NOD2_220066_at_tn.png
| Function = {{GNF_GO|id=GO:0000166 |text = nucleotide binding}} {{GNF_GO|id=GO:0005524 |text = ATP binding}} {{GNF_GO|id=GO:0019899 |text = enzyme binding}} {{GNF_GO|id=GO:0019901 |text = protein kinase binding}} {{GNF_GO|id=GO:0042834 |text = peptidoglycan binding}} {{GNF_GO|id=GO:0050700 |text = CARD domain binding}}
| Component = {{GNF_GO|id=GO:0005622 |text = intracellular}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}} {{GNF_GO|id=GO:0005829 |text = cytosol}} {{GNF_GO|id=GO:0005886 |text = plasma membrane}} {{GNF_GO|id=GO:0031982 |text = vesicle}}
| Process = {{GNF_GO|id=GO:0001816 |text = cytokine production}} {{GNF_GO|id=GO:0007242 |text = intracellular signaling cascade}} {{GNF_GO|id=GO:0008063 |text = Toll signaling pathway}} {{GNF_GO|id=GO:0016045 |text = detection of bacterium}} {{GNF_GO|id=GO:0042742 |text = defense response to bacterium}} {{GNF_GO|id=GO:0042981 |text = regulation of apoptosis}} {{GNF_GO|id=GO:0043123 |text = positive regulation of I-kappaB kinase/NF-kappaB cascade}} {{GNF_GO|id=GO:0050718 |text = positive regulation of interleukin-1 beta secretion}} {{GNF_GO|id=GO:0051092 |text = activation of NF-kappaB transcription factor}} {{GNF_GO|id=GO:0051259 |text = protein oligomerization}}
  | Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 64127
    | Hs_Ensembl = ENSG00000167207
    | Hs_RefseqProtein = NP_071445
    | Hs_RefseqmRNA = NM_022162
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 16
    | Hs_GenLoc_start = 49288551
    | Hs_GenLoc_end = 49324488
    | Hs_Uniprot = Q9HC29
    | Mm_EntrezGene = 257632
    | Mm_Ensembl = ENSMUSG00000055994
    | Mm_RefseqmRNA = XM_989552
    | Mm_RefseqProtein = XP_994646
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 8
    | Mm_GenLoc_start = 91537452
    | Mm_GenLoc_end = 91578579
    | Mm_Uniprot = Q2PZA3
  }}
}}


'''NOD2''' ('''n'''ucleotide-binding '''o'''ligomerization '''d'''omain containing '''2''') is a [[protein]], also known as the [[CARD domain|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 protein]]s of plants and recognizes molecules containing the specific structure called [[muramyl dipeptide]] (MDP) that is found in certain [[bacteria]].<ref>{{cite journal |author=Kufer T, Banks D, Philpott D |title=Innate immune sensing of microbes by Nod proteins |journal=Ann. N. Y. Acad. Sci. |volume=1072 |issue= |pages=19-27 |year=2006 |pmid=17057187}}</ref>
== Structure ==
[[Image:Nod2 protein.png|thumbnail|left|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<ref name="pmid22319155">{{cite journal | vauthors = Nakagome S, Mano S, Kozlowski L, Bujnicki JM, Shibata H, Fukumaki Y, Kidd JR, Kidd KK, Kawamura S, Oota H | title = Crohn's disease risk alleles on the NOD2 locus have been maintained by natural selection on standing variation | journal = Molecular Biology and Evolution | volume = 29 | issue = 6 | pages = 1569–85 | date = Jun 2012 | pmid = 22319155 | pmc = 3697811 | doi = 10.1093/molbev/mss006 }}</ref>]]


The ''NOD2'' gene is linked to inflammatory diseases such as [[inflammatory bowel disease]]/[[Crohn's Disease]] and [[Blau syndrome]].<ref>{{cite journal |author=Radford-Smith G, Pandeya N |title=Associations between NOD2/CARD15 genotype and phenotype in Crohn's disease--Are we there yet? |journal=World J. Gastroenterol. |volume=12 |issue=44 |pages=7097-103 |year=2006 |pmid=17131470}}</ref><ref>{{cite journal |author=Kim T, Payne U, Zhang X, Iwanaga Y, Davey M, Rosenbaum J, Inman R |title=Altered host:pathogen interactions conferred by the Blau syndrome mutation of NOD2 |journal=Rheumatol. Int. |volume=27 |issue=3 |pages=257-62 |year=2007 |pmid=17096091}}</ref>
The [[C-terminus|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-like receptor|NOD domain]] involved in protein self-oligomerization. The [[N-terminus|N-terminal]] portion contains two [[CARD domain]]s known to play a role in [[apoptosis]] and [[NF-κB]] activation pathways.<ref name="pmid11087742">{{cite journal | vauthors = Ogura Y, Inohara N, Benito A, Chen FF, Yamaoka S, Nunez G | title = Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-kappaB | journal = The Journal of Biological Chemistry | volume = 276 | issue = 7 | pages = 4812–8 | date = Feb 2001 | pmid = 11087742 | doi = 10.1074/jbc.M008072200 }}</ref>
It is located on [[chromosome 16 (human)|chromosome 16]] in humans.


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{PBB_Summary
| section_title =  
| summary_text = This gene is a member of the Nod1/Apaf-1 family and encodes a protein with two caspase recruitment (CARD) domains and six leucine-rich repeats (LRRs). The protein is primarily expressed in the peripheral blood leukocytes. It plays a role in the immune response to intracellular bacterial lipopolysaccharides (LPS) by recognizing the muramyl dipeptide (MDP) derived from them and activating the NFKB protein. Mutations in this gene have been associated with Crohn disease and Blau syndrome.<ref>{{cite web | title = Entrez Gene: NOD2 nucleotide-binding oligomerization domain containing 2| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=64127| accessdate = }}</ref>
}}


==References==
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 domain]]s (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.<ref name = "entrez">{{cite web | title = Entrez Gene: NOD2 nucleotide-binding oligomerization domain containing 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=64127| accessdate = }}</ref>
{{reflist|2}}


==Further reading==
== Clinical significance ==
{{refbegin | 2}}
 
{{PBB_Further_reading
Mutations in this gene have been associated with [[Crohn's disease]],<ref name="pmid22319155"/> [[Blau syndrome]], severe pulmonary [[sarcoidosis]] <ref>{{cite journal | vauthors = Sato H, Williams HR, Spagnolo P, Abdallah A, Ahmad T, Orchard TR, Copley SJ, Desai SR, Wells AU, du Bois RM, Welsh KI | title = CARD15/NOD2 polymorphisms are associated with severe pulmonary sarcoidosis.| journal = Eur Respir J | volume = 35 | issue = 2 | pages = 324–30 | date = Feb 2010 | pmid = 19679608 | doi = 10.1183/09031936.00010209}}</ref> and [[Graft-versus-host disease]].<ref>{{cite journal | vauthors = Zhao H, Jia M, Wang Z, Cheng Y, Luo Z, Chen Y, Xu X, Yang S, Tang Y | title = Association between NOD2 single nucleotide polymorphisms and Grade III-IV acute graft-versus-host disease: A meta-analysis | journal = Hematology | volume = 20 | issue = 5 | pages = 254–62 | date = Jun 2015 | pmid = 25248089 | doi = 10.1179/1607845414Y.0000000202 }}</ref>
| citations =  
 
*{{cite journal | author=Punchard NA |title=Overview: Nod2, cause of, or contributor to, Crohn's disease. |journal=Current opinion in investigational drugs (London, England : 2000) |volume=2 |issue= 10 |pages= 1378-81 |year= 2002 |pmid= 11890351 |doi=  }}
The NOD2 gene is linked to inflammatory diseases such as [[Inflammatory bowel disease]]/[[Crohn's Disease]] and [[Blau syndrome]].<ref name="pmid17131470">{{cite journal | vauthors = Radford-Smith G, Pandeya N | title = Associations between NOD2/CARD15 genotype and phenotype in Crohn's disease--Are we there yet? | journal = World Journal of Gastroenterology | volume = 12 | issue = 44 | pages = 7097–103 | date = Nov 2006 | pmid = 17131470 | doi = 10.3748/wjg.v12.i44.7097 }}</ref><ref name="pmid17096091">{{cite journal | vauthors = Kim TH, Payne U, Zhang X, Iwanaga Y, Davey MP, Rosenbaum JT, Inman RD | title = Altered host:pathogen interactions conferred by the Blau syndrome mutation of NOD2 | journal = Rheumatology International | volume = 27 | issue = 3 | pages = 257–62 | date = Jan 2007 | pmid = 17096091 | doi = 10.1007/s00296-006-0250-0 }}</ref>
*{{cite journal | author=Satsangi J, Morecroft J, Shah NB, Nimmo E |title=Genetics of inflammatory bowel disease: scientific and clinical implications. |journal=Best practice & research. Clinical gastroenterology |volume=17 |issue= 1 |pages= 3-18 |year= 2003 |pmid= 12617879 |doi= }}
 
*{{cite journal | author=Rosenbaum JT, Planck SR, Davey MP, ''et al.'' |title=With a mere nod, uveitis enters a new era. |journal=Am. J. Ophthalmol. |volume=136 |issue= 4 |pages= 729-32 |year= 2003 |pmid= 14516815 |doi= }}
== Interactions ==
*{{cite journal | author=Kurokawa T, Kikuchi T, Ohta K, ''et al.'' |title=Ocular manifestations in Blau syndrome associated with a CARD15/Nod2 mutation. |journal=Ophthalmology |volume=110 |issue= 10 |pages= 2040-4 |year= 2003 |pmid= 14522785 |doi= 10.1016/S0161-6420(03)00717-6 }}
 
*{{cite journal | author=Girardin SE, Hugot JP, Sansonetti PJ |title=Lessons from Nod2 studies: towards a link between Crohn's disease and bacterial sensing. |journal=Trends Immunol. |volume=24 |issue= 12 |pages= 652-8 |year= 2004 |pmid= 14644139 |doi= }}
NOD2 has been shown to [[Protein–protein interaction|interact]] with [[NLRC4]].<ref name="pmid15107016">{{cite journal | vauthors = Damiano JS, Oliveira V, Welsh K, Reed JC | title = Heterotypic interactions among NACHT domains: implications for regulation of innate immune responses | journal = The Biochemical Journal | volume = 381 | issue = Pt 1 | pages = 213–9 | date = Jul 2004 | pmid = 15107016 | pmc = 1133779 | doi = 10.1042/BJ20031506 }}</ref><ref name="pmid11472070">{{cite journal | vauthors = Damiano JS, Stehlik C, Pio F, Godzik A, Reed JC | title = CLAN, a novel human CED-4-like gene | journal = Genomics | volume = 75 | issue = 1-3 | pages = 77–83 | date = Jul 2001 | pmid = 11472070 | doi = 10.1006/geno.2001.6579 }}</ref>
*{{cite journal | author=Newman B, Siminovitch K |title=Inflammatory bowel disease: Crohn's disease and the success of NODern genetics. |journal=Clinical and investigative medicine. Médecine clinique et experimentale |volume=26 |issue= 6 |pages= 303-14 |year= 2004 |pmid= 14690304 |doi=  }}
 
*{{cite journal | author=Oostenbrug LE, van Dullemen HM, te Meerman GJ, Jansen PL |title=IBD and genetics: new developments. |journal=Scand. J. Gastroenterol. Suppl. |volume= |issue= 239 |pages= 63-8 |year= 2004 |pmid= 14743885 |doi=  }}
NOD2 has also been shown to bind to [[VISA (gene)|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.<ref>{{cite journal | vauthors = Sabbah A, Chang TH, Harnack R, Frohlich V, Tominaga K, Dube PH, Xiang Y, Bose S | title = Activation of innate immune antiviral responses by Nod2 | journal = Nature Immunology | volume = 10 | issue = 10 | pages = 1073–80 | date = Oct 2009 | pmid = 19701189 | pmc = 2752345 | doi = 10.1038/ni.1782 }}</ref>
*{{cite journal | author=Kambe N, Nishikomori R, Kanazawa N |title=The cytosolic pattern-recognition receptor Nod2 and inflammatory granulomatous disorders. |journal=J. Dermatol. Sci. |volume=39 |issue= 2 |pages= 71-80 |year= 2005 |pmid= 15927452 |doi= 10.1016/j.jdermsci.2005.04.001 }}
 
*{{cite journal | author=Newman B, Siminovitch KA |title=Recent advances in the genetics of inflammatory bowel disease. |journal=Curr. Opin. Gastroenterol. |volume=21 |issue= 4 |pages= 401-7 |year= 2005 |pmid= 15930978 |doi=  }}
== See also ==
*{{cite journal | author=Martinon F, Tschopp J |title=NLRs join TLRs as innate sensors of pathogens. |journal=Trends Immunol. |volume=26 |issue= 8 |pages= 447-54 |year= 2006 |pmid= 15967716 |doi= 10.1016/j.it.2005.06.004 }}
* [[Mifamurtide]], a NOD2 activator for the treatment of [[osteosarcoma]]
*{{cite journal | author=Strober W, Murray PJ, Kitani A, Watanabe T |title=Signalling pathways and molecular interactions of NOD1 and NOD2. |journal=Nat. Rev. Immunol. |volume=6 |issue= 1 |pages= 9-20 |year= 2006 |pmid= 16493424 |doi= 10.1038/nri1747 }}
 
*{{cite journal | author=Cavanaugh J |title=NOD2: ethnic and geographic differences. |journal=World J. Gastroenterol. |volume=12 |issue= 23 |pages= 3673-7 |year= 2006 |pmid= 16773683 |doi= }}
== References ==
*{{cite journal | author=Hugot JP |title=CARD15/NOD2 mutations in Crohn's disease. |journal=Ann. N. Y. Acad. Sci. |volume=1072 |issue= |pages= 9-18 |year= 2006 |pmid= 17057186 |doi= 10.1196/annals.1326.011 }}
{{Reflist|33em}}
*{{cite journal | author=Vignal C, Singer E, Peyrin-Biroulet L, ''et al.'' |title=How NOD2 mutations predispose to Crohn's disease? |journal=Microbes Infect. |volume=9 |issue= 5 |pages= 658-63 |year= 2007 |pmid= 17379562 |doi= 10.1016/j.micinf.2007.01.016 }}
 
*{{cite journal | author=Quaglietta L, te Velde A, Staiano A, ''et al.'' |title=Functional consequences of NOD2/CARD15 mutations in Crohn disease. |journal=J. Pediatr. Gastroenterol. Nutr. |volume=44 |issue= 5 |pages= 529-39 |year= 2007 |pmid= 17460484 |doi= 10.1097/MPG.0b013e31803815ee }}
== Further reading ==
*{{cite journal | author=van der Linde K, Boor PP, Houwing-Duistermaat JJ, ''et al.'' |title=CARD15 mutations in Dutch familial and sporadic inflammatory bowel disease and an overview of European studies. |journal=European journal of gastroenterology & hepatology |volume=19 |issue= 6 |pages= 449-59 |year= 2007 |pmid= 17489054 |doi= 10.1097/01.meg.0000236887.44214.6a }}
{{refbegin|33em}}
}}
* {{cite journal | vauthors = Punchard NA | title = Overview: Nod2, cause of, or contributor to, Crohn's disease | journal = Current Opinion in Investigational Drugs | volume = 2 | issue = 10 | pages = 1378–81 | date = Oct 2001 | pmid = 11890351 | doi =  }}
* {{cite journal | vauthors = Satsangi J, Morecroft J, Shah NB, Nimmo E | title = Genetics of inflammatory bowel disease: scientific and clinical implications | journal = Best Practice & Research. Clinical Gastroenterology | volume = 17 | issue = 1 | pages = 3–18 | date = Feb 2003 | pmid = 12617879 | doi = 10.1053/bega.2002.0349 }}
* {{cite journal | vauthors = Rosenbaum JT, Planck SR, Davey MP, Iwanaga Y, Kurz DE, Martin TM | title = With a mere nod, uveitis enters a new era | journal = American Journal of Ophthalmology | volume = 136 | issue = 4 | pages = 729–32 | date = Oct 2003 | pmid = 14516815 | doi = 10.1016/S0002-9394(03)00569-5 }}
* {{cite journal | vauthors = Kurokawa T, Kikuchi T, Ohta K, Imai H, Yoshimura N | title = Ocular manifestations in Blau syndrome associated with a CARD15/Nod2 mutation | journal = Ophthalmology | volume = 110 | issue = 10 | pages = 2040–4 | date = Oct 2003 | pmid = 14522785 | doi = 10.1016/S0161-6420(03)00717-6 }}
* {{cite journal | vauthors = Girardin SE, Hugot JP, Sansonetti PJ | title = Lessons from Nod2 studies: towards a link between Crohn's disease and bacterial sensing | journal = Trends in Immunology | volume = 24 | issue = 12 | pages = 652–8 | date = Dec 2003 | pmid = 14644139 | doi = 10.1016/j.it.2003.10.007 }}
* {{cite journal | vauthors = Newman B, Siminovitch K | title = Inflammatory bowel disease: Crohn's disease and the success of NODern genetics | journal = Clinical and Investigative Medicine. Médecine Clinique Et Experimentale | volume = 26 | issue = 6 | pages = 303–14 | date = Dec 2003 | pmid = 14690304 | doi =  }}
* {{cite journal | vauthors = Oostenbrug LE, van Dullemen HM, te Meerman GJ, Jansen PL | title = IBD and genetics: new developments | journal = Scandinavian Journal of Gastroenterology. Supplement | volume = 38| issue = 239 | pages = 63–8 | year = 2003 | pmid = 14743885 | doi =  10.1080/00855920310002717}}
* {{cite journal | vauthors = Kambe N, Nishikomori R, Kanazawa N | title = The cytosolic pattern-recognition receptor Nod2 and inflammatory granulomatous disorders | journal = Journal of Dermatological Science | volume = 39 | issue = 2 | pages = 71–80 | date = Aug 2005 | pmid = 15927452 | doi = 10.1016/j.jdermsci.2005.04.001 }}
* {{cite journal | vauthors = Newman B, Siminovitch KA | title = Recent advances in the genetics of inflammatory bowel disease | journal = Current Opinion in Gastroenterology | volume = 21 | issue = 4 | pages = 401–7 | date = Jul 2005 | pmid = 15930978 | doi =  }}
* {{cite journal | vauthors = Martinon F, Tschopp J | title = NLRs join TLRs as innate sensors of pathogens | journal = Trends in Immunology | volume = 26 | issue = 8 | pages = 447–54 | date = Aug 2005 | pmid = 15967716 | doi = 10.1016/j.it.2005.06.004 }}
* {{cite journal | vauthors = Strober W, Murray PJ, Kitani A, Watanabe T | title = Signalling pathways and molecular interactions of NOD1 and NOD2 | journal = Nature Reviews. Immunology | volume = 6 | issue = 1 | pages = 9–20 | date = Jan 2006 | pmid = 16493424 | doi = 10.1038/nri1747 }}
* {{cite journal | vauthors = Cavanaugh J | title = NOD2: ethnic and geographic differences | journal = World Journal of Gastroenterology | volume = 12 | issue = 23 | pages = 3673–7 | date = Jun 2006 | pmid = 16773683 | doi = 10.3748/wjg.v12.i23.3673 }}
* {{cite journal | vauthors = Hugot JP | title = CARD15/NOD2 mutations in Crohn's disease | journal = Annals of the New York Academy of Sciences | volume = 1072 | issue = 1 | pages = 9–18 | date = Aug 2006 | pmid = 17057186 | doi = 10.1196/annals.1326.011 }}
* {{cite journal | vauthors = Vignal C, Singer E, Peyrin-Biroulet L, Desreumaux P, Chamaillard M | title = How NOD2 mutations predispose to Crohn's disease? | journal = Microbes and Infection / Institut Pasteur | volume = 9 | issue = 5 | pages = 658–63 | date = Apr 2007 | pmid = 17379562 | doi = 10.1016/j.micinf.2007.01.016 }}
* {{cite journal | vauthors = Quaglietta L, te Velde A, Staiano A, Troncone R, Hommes DW | title = Functional consequences of NOD2/CARD15 mutations in Crohn disease | journal = Journal of Pediatric Gastroenterology and Nutrition | volume = 44 | issue = 5 | pages = 529–39 | date = May 2007 | pmid = 17460484 | doi = 10.1097/MPG.0b013e31803815ee }}
* {{cite journal | vauthors = van der Linde K, Boor PP, Houwing-Duistermaat JJ, Crusius BJ, Wilson PJ, Kuipers EJ, de Rooij FW | title = CARD15 mutations in Dutch familial and sporadic inflammatory bowel disease and an overview of European studies | journal = European Journal of Gastroenterology & Hepatology | volume = 19 | issue = 6 | pages = 449–59 | date = Jun 2007 | pmid = 17489054 | doi = 10.1097/01.meg.0000236887.44214.6a }}
{{refend}}
{{refend}}


==External links==
{{NOD-like receptors}}
http://www.genecards.org/cgi-bin/carddisp.pl?gene=CARD15&search=nod2


[[Category:Genes]]
[[Category:Human genes]]
[[Category:LRR proteins]]
[[Category:LRR proteins]]
 
[[Category:NOD-like receptors]]
[[es:NOD2]]
{{WikiDoc Sources}}

Revision as of 18:35, 4 December 2017

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Identifiers
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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
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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

File:Nod2 protein.png
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]

See also

References

  1. ↑ 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.
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ 4.0 4.1 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.
  5. ↑ 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.
  6. ↑ "Entrez Gene: NOD2 nucleotide-binding oligomerization domain containing 2".
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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. doi:10.3748/wjg.v12.i44.7097. PMID 17131470.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.

Further reading

  • 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. doi:10.3748/wjg.v12.i23.3673. 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.
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