Wikipedia

NOD2

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.[5][6] NOD2 plays an important role in the immune system. It recognizes bacterial molecules (peptidoglycans) and stimulates an immune reaction.[7]

NOD2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesNOD2, ACUG, BLAU, CARD15, CD, CLR16.3, IBD1, NLRC2, NOD2B, PSORAS1, nucleotide binding oligomerization domain containing 2, BLAUS, YAOS
External IDsOMIM: 605956; MGI: 2429397; HomoloGene: 11156; GeneCards: NOD2; OMA:NOD2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

64127

257632

Ensembl

ENSG00000167207

ENSMUSG00000055994

UniProt

Q9HC29

Q80SY9

RefSeq (mRNA)

NM_001293557
NM_022162
NM_001370466

NM_145857

RefSeq (protein)

NP_001280486
NP_071445
NP_001357395

NP_665856

Location (UCSC)Chr 16: 50.69 – 50.73 MbChr 8: 89.37 – 89.42 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[8]

Structure

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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[9]

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.[10]

Function

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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.[11]

Clinical significance

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Mutations in this gene have been associated with serious autoimmune diseases like Crohn's disease,[9] Blau syndrome, pulmonary sarcoidosis[12] and Graft-versus-host disease.[13][14][15]

Loss of function mutations of NOD2 have been associated with better response to cancer therapy with PD-1/PD-L1 immune checkpoint blockade.[16]

Interactions

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NOD2 has been shown to interact with NLRC4.[17][18]

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.[19]

See also

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References

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  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000167207 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000055994 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Gilberts EC, Greenstein AJ, Katsel P, Harpaz N, Greenstein RJ (December 1994). "Molecular evidence for two forms of Crohn disease". Proceedings of the National Academy of Sciences of the United States of America. 91 (26): 12721–12724. Bibcode:1994PNAS...9112721G. doi:10.1073/pnas.91.26.12721. PMC 45511. PMID 7809109.
  6. ↑ Hugot JP, Laurent-Puig P, Gower-Rousseau C, Olson JM, Lee JC, Beaugerie L, et al. (February 1996). "Mapping of a susceptibility locus for Crohn's disease on chromosome 16". Nature. 379 (6568): 821–823. Bibcode:1996Natur.379..821H. doi:10.1038/379821a0. PMID 8587604. S2CID 4311407.
  7. ↑ Mahla RS, Reddy MC, Prasad DV, Kumar H (September 2013). "Sweeten PAMPs: Role of Sugar Complexed PAMPs in Innate Immunity and Vaccine Biology". Frontiers in Immunology. 4: 248. doi:10.3389/fimmu.2013.00248. PMC 3759294. PMID 24032031.
  8. ↑ Kufer TA, Banks DJ, Philpott DJ (August 2006). "Innate immune sensing of microbes by Nod proteins". Annals of the New York Academy of Sciences. 1072 (1): 19–27. Bibcode:2006NYASA1072...19K. doi:10.1196/annals.1326.020. PMID 17057187. S2CID 20217610.
  9. 1 2 Nakagome S, Mano S, Kozlowski L, Bujnicki JM, Shibata H, Fukumaki Y, et al. (June 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): 1569–1585. doi:10.1093/molbev/mss006. PMC 3697811. PMID 22319155.
  10. ↑ Ogura Y, Inohara N, Benito A, Chen FF, Yamaoka S, Nunez G (February 2001). "Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-kappaB". The Journal of Biological Chemistry. 276 (7): 4812–4818. doi:10.1074/jbc.M008072200. PMID 11087742.
  11. ↑ "Entrez Gene: NOD2 nucleotide-binding oligomerization domain containing 2".
  12. ↑ Sato H, Williams HR, Spagnolo P, Abdallah A, Ahmad T, Orchard TR, et al. (February 2010). "CARD15/NOD2 polymorphisms are associated with severe pulmonary sarcoidosis". The European Respiratory Journal. 35 (2): 324–330. doi:10.1183/09031936.00010209. hdl:11380/983383. PMID 19679608.
  13. ↑ Zhao H, Jia M, Wang Z, Cheng Y, Luo Z, Chen Y, et al. (June 2015). "Association between NOD2 single nucleotide polymorphisms and Grade III-IV acute graft-versus-host disease: A meta-analysis". Hematology. 20 (5): 254–262. doi:10.1179/1607845414Y.0000000202. PMID 25248089. S2CID 206850232.
  14. ↑ Radford-Smith G, Pandeya N (November 2006). "Associations between NOD2/CARD15 genotype and phenotype in Crohn's disease--Are we there yet?". World Journal of Gastroenterology. 12 (44): 7097–7103. doi:10.3748/wjg.v12.i44.7097. PMC 4087769. PMID 17131470.
  15. ↑ Kim TH, Payne U, Zhang X, Iwanaga Y, Davey MP, Rosenbaum JT, et al. (January 2007). "Altered host:pathogen interactions conferred by the Blau syndrome mutation of NOD2". Rheumatology International. 27 (3): 257–262. doi:10.1007/s00296-006-0250-0. PMID 17096091. S2CID 23739992.
  16. ↑ Barnet MB, Jackson KJ, Masle-Farquhar E, Russell A, Burnett DL, Chye A, et al. (July 2025). "Common inherited loss-of-function mutations in the innate sensor NOD2 contribute to exceptional immune response to cancer immunotherapy". Proceedings of the National Academy of Sciences of the United States of America. 122 (28) e2314258122. doi:10.1073/pnas.2314258122. PMC 12280981. PMID 40623177.
  17. ↑ Damiano JS, Oliveira V, Welsh K, Reed JC (July 2004). "Heterotypic interactions among NACHT domains: implications for regulation of innate immune responses". The Biochemical Journal. 381 (Pt 1): 213–219. doi:10.1042/BJ20031506. PMC 1133779. PMID 15107016.
  18. ↑ Damiano JS, Stehlik C, Pio F, Godzik A, Reed JC (July 2001). "CLAN, a novel human CED-4-like gene". Genomics. 75 (1–3): 77–83. doi:10.1006/geno.2001.6579. PMID 11472070.
  19. ↑ Sabbah A, Chang TH, Harnack R, Frohlich V, Tominaga K, Dube PH, et al. (October 2009). "Activation of innate immune antiviral responses by Nod2". Nature Immunology. 10 (10): 1073–1080. doi:10.1038/ni.1782. PMC 2752345. PMID 19701189.

Further reading

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