NOD2

NOD2
Identifiers
Aliases	NOD2, ACUG, BLAU, CARD15, CD, CLR16.3, IBD1, NLRC2, NOD2B, PSORAS1, nucleotide binding oligomerization domain containing 2, BLAUS, YAOS
External IDs	OMIM: 605956; MGI: 2429397; GeneCards: NOD2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 5IRL, 5IRM, 5IRN
Gene location (Human) Chr. Chromosome 16 (human) Band 16q12.1 Start 50,693,588 bp End 50,734,041 bp
Gene location (Mouse) Chr. Chromosome 8 (mouse) Band 8|8 C3 Start 89,373,943 bp End 89,415,102 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte granulocyte blood skin of leg skin of abdomen vulva human penis cartilage tissue bone marrow cell vagina Top expressed in granulocyte secondary oocyte primary oocyte zygote embryo esophagus zone of skin lip quadriceps femoris muscle duodenum More reference expression data BioGPS More reference expression data
Gene ontology Molecular function Hsp90 protein binding nucleotide binding Hsp70 protein binding protein binding peptidoglycan binding enzyme binding actin binding CARD domain binding ATP binding protein kinase binding muramyl dipeptide binding protein-containing complex binding Cellular component cytoplasm cytosol vesicle membrane plasma membrane cell surface basolateral plasma membrane COP9 signalosome cytoskeleton Golgi apparatus mitochondrion protein-containing complex Biological process positive regulation of prostaglandin-endoperoxide synthase activity regulation of apoptotic process defense response detection of biotic stimulus cytokine production involved in immune response positive regulation of cytokine production involved in inflammatory response intracellular signal transduction detection of muramyl dipeptide positive regulation of interleukin-10 production positive regulation of epithelial cell proliferation immune system process positive regulation of oxidoreductase activity response to muramyl dipeptide positive regulation of prostaglandin-E synthase activity positive regulation of JNK cascade positive regulation of nitric-oxide synthase biosynthetic process positive regulation of NIK/NF-kappaB signaling positive regulation of phosphatidylinositol 3-kinase activity positive regulation of gamma-delta T cell activation cellular response to muramyl dipeptide JNK cascade negative regulation of macrophage apoptotic process positive regulation of dendritic cell antigen processing and presentation nucleotide-binding oligomerization domain containing 2 signaling pathway maintenance of gastrointestinal epithelium defense response to bacterium positive regulation of NF-kappaB transcription factor activity positive regulation of interleukin-8 production detection of bacterium positive regulation of interleukin-1 beta production regulation of inflammatory response positive regulation of interleukin-6 production protein complex oligomerization positive regulation of tumor necrosis factor production positive regulation of ERK1 and ERK2 cascade positive regulation of I-kappaB kinase/NF-kappaB signaling positive regulation of B cell activation positive regulation of interleukin-17 production positive regulation of type 2 immune response nucleotide-binding oligomerization domain containing signaling pathway positive regulation of stress-activated MAPK cascade positive regulation of Notch signaling pathway positive regulation of transcription by RNA polymerase II cellular response to organic cyclic compound positive regulation of cell population proliferation innate immune response response to nutrient positive regulation of dendritic cell cytokine production positive regulation of protein K63-linked ubiquitination cellular response to peptidoglycan positive regulation of MAP kinase activity interleukin-1-mediated signaling pathway cellular response to lipopolysaccharide Sources:Amigo / QuickGO
Orthologs Databases NCBI: entry; OMA: entry Species Human Mouse 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 Mb Chr 8: 89.37 – 89.42 Mb PubMed search
Wikidata
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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. 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.

Structure

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.

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.

Clinical significance

Mutations in this gene have been associated with serious autoimmune diseases like Crohn's disease, Blau syndrome, pulmonary sarcoidosis and Graft-versus-host disease.

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

Interactions

NOD2 has been shown to interact with NLRC4.

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.

See also

• Mifamurtide, a NOD2 activator for the treatment of osteosarcoma

References

Further reading