NOD2

NOD2 protein
other names	Nod2b, CARD15
Properties of human protein
Mass / length primary structure	1,040 amino acids , 115,283 Da
Identifier
Gene name	NOD2
External IDs	GeneCards :  NOD2 OMIM :  605956 UniProt :  Q9HC29
Orthologue
	human	mouse
Entrez	64127	257632
Ensemble	ENSG00000167207
UniProt	D6CHF9	Q8K3Z0
Refseq (mRNA)	NM_001293557.1
Refseq (protein)	NP_001280486.1
Gene locus
PubMed search	64127	257632

The protein NOD2 is a receptor for foreign substances in the innate immune system of mammals , a so-called pattern recognition receptor . NOD2 is mainly of monocytes produced dendritic cells, and intestinal epithelial cells, recognizes in particular the bacterial muramyl dipeptide and starts after detecting the foreign substances on RICK and IKK-gamma the NF-kappa B - signal . Mutations in NOD2 - gene are responsible for the rare hereditary Blau syndrome and early onset sarcoidosis (EOS) responsible for increased risk of developing as well as ulcerative colitis or Crohn's disease cancer. Furthermore, the presence of mutations in the NOD2 gene doubles the risk of developing an intestinal graft versus host reaction after a bone marrow or blood stem cell transplant . If both the bone marrow donor and the bone marrow recipient carry mutations in the NOD2 gene, the risk adds up.

Recent findings indicate that NOD2 recognizes not only bacterial but also viral patterns and, as a result, activates the viral immune response via MAVS and IRF3. Together with NOD1, NOD2 is a central component of the innate immune system.

literature

• Y. Ogura, N. Inohara et al: Nod2, a Nod1 / Apaf-1 family member that is restricted to monocytes and activates NF-kappaB. In: The Journal of biological chemistry . Volume 276, Number 7, February 2001, pp. 4812-4818, ISSN  0021-9258 . doi: 10.1074 / jbc.M008072200 . PMID 11087742 .
• O. Gutierrez, C. Pipaon, N. Inohara et al .: Induction of Nod2 in myelomonocytic and intestinal epithelial cells via nuclear factor-kappa B activation. In: The Journal of Biological Chemistry. 277 (44), November 2002, pp. 41701-41705. ISSN  0021-9258 . PMID 12194982 .
• J. Hampe, A. Cuthbert, PJ Croucher, MM Mirza, S. Mascheretti, S. Fisher, H. Frenzel, K. King, A. Hasselmeyer, AJ MacPherson, S. Bridger, S. van Deventer, A. Forbes, S. Nikolaus, JE Lennard-Jones, UR Foelsch, M. Krawczak, C. Lewis, S. Scheiber, CG Mathew: Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populations. In: Lancet. 357 (9272), Jun 16, 2001, pp. 1925-1928. PMID 11425413 .
• P. Rosenstiel, M. Fantini, K. Bräutigam et al: TNF-alpha and IFN-gamma regulate the expression of NOD2 (CARD15) gene in human intestinal epithelial cells. In: Gastroenterology. 124, 2003, pp. 1001-1009. ISSN  0016-5085 . PMID 12671897 .
• AG Kutikhin: Role of NOD1 / CARD4 and NOD2 / CARD15 gene polymorphisms in cancer etiology. In: Human immunology. Volume 72, Number 10, October 2011, pp. 955-968, ISSN  1879-1166 . doi: 10.1016 / j.humimm.2011.06.003 . PMID 21745515 . (Review).
• L. Le Bourhis, S. Benko, SE Girardin: Nod1 and Nod2 in innate immunity and human inflammatory disorders. In: Biochemical Society transactions . Volume 35, Pt 6, December 2007, pp. 1479-1484, ISSN  0300-5127 . doi: 10.1042 / BST0351479 . PMID 18031249 . (Review).
• P. Rosenstiel, S. Schreiber: NOD-like receptors-pivotal guardians of the immunological integrity of barrier organs. In: Advances in Experimental Medicine and Biology . Volume 653, 2009, pp. 35-47, ISSN  0065-2598 . PMID 19799110 . (Review).
• TD Kanneganti, M. Lamkanfi, G. Núñez: Intracellular NOD-like receptors in host defense and disease. In: Immunity. Volume 27, Number 4, October 2007, pp. 549-559, ISSN  1074-7613 . doi: 10.1016 / j.immuni.2007.10.002 . PMID 17967410 . (Review).
• K. Geddes, JG Magalhães, SE Girardin: Unleashing the therapeutic potential of NOD-like receptors. In: Nature Reviews Drug Discovery . Volume 8, Number 6, June 2009, pp. 465-479, ISSN  1474-1784 . doi: 10.1038 / nrd2783 . PMID 19483708 . (Review).

Individual evidence

1. ↑ Y. Ogura, N. Inohara, A. Benito, FF Chen, S. Yamaoka, G. Nunez: Nod2, a Nod1 / Apaf-1 family member did is restricted to monocytes and the activates NF-kappaB. In: The Journal of biological chemistry. Volume 276, Number 7, February 2001, ISSN  0021-9258 , pp. 4812-4818, doi: 10.1074 / jbc.M008072200 . PMID 11087742 .
2. ↑ O. Gutierrez, C. Pipaon, N. Inohara, A. Fontalba, Y. Ogura, F. Prosper, G. Nunez, JL Fernandez-Luna: Induction of Nod2 in myelomonocytic and intestinal epithelial cells via nuclear factor-kappa B activation . In: The Journal of biological chemistry. Volume 277, Number 44, November 2002, ISSN  0021-9258 , pp. 41701-41705, doi: 10.1074 / jbc.M206473200 . PMID 12194982 .
3. ^ P. Rosenstiel, M. Fantini, K. Bräutigam, T. Kühbacher, GH Waetzig, D. Seegert, S. Schreiber: TNF-alpha and IFN-gamma regulate the expression of the NOD2 (CARD15) gene in human intestinal epithelial cells . In: Gastroenterology. Volume 124, Number 4, April 2003, ISSN  0016-5085 , pp. 1001-1009, doi: 10.1053 / gast.2003.50157 . PMID 12671897 .
4. ↑ UniProt Q9HC29
5. ^ E. Holler, G. Rogler, H. Herfarth, J. Brenmoehl, PJ Wild, J. Hahn, G. Eissner, J. Schoelmerich, R. Andreesen: Both donor and recipient NOD2 / CARD15 mutations associate with transplant-related mortality and GvHD following allogeneic stem cell transplantation. In: Blood. Volume 104, number 3, 2004, pp. 889-894, doi: 10.1182 / blood-2003-10-3543 .
6. ↑ K. Landfried, F. Bataille, G. Rogler, J. Brenmoehl, K. Kosovac, D. Wolff, I. Hilgendorf, J. Hahn, M. Edinger, P. Hoffmann, F. Obermeier, J. Schoelmerich, R Andreesen, E. Holler: Recipient NOD2 / CARD15 status affects cellular infiltrates in human intestinal graft-versus-host disease. In: Clinical and Experimental Immunology. Volume 159, number 1, 2010, pp. 87-92, doi: 10.1111 / j.1365-2249.2009.04049.x .
7. ↑ A. Sabbah, TH Chang et al: Activation of innate immune antiviral responses by Nod2. In: Nature Immunology . Volume 10, Number 10, October 2009, pp. 1073-1080, ISSN  1529-2916 . doi: 10.1038 / ni.1782 . PMID 19701189 . PMC 2752345 (free full text).