Homo sapiens Protein: NOD2
InnateDB Protein IDBP-30656.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol NOD2
Protein Name nucleotide-binding oligomerization domain containing 2
Species Homo sapiens
Ensembl Protein ENSP00000300589
InnateDB Gene IDBG-30654 (NOD2)
Protein Structure
UniProt Annotation
Function Recognizes muramyl dipeptide (MDP) constituents of bacterial peptidoglycans and plays a key role in gastrointestinal immunity: upon stimulation, binds the proximal adapter receptor- interacting RIPK2, which recruits ubiquitin ligases as XIAP, BIRC2, BIRC3 and the LUBAC complex, triggering activation of MAP kinases and activation of NF-kappa-B signaling, leading to activate the transcription of hundreds of genes involved in immune response. {ECO:0000269PubMed:23806334}.
Subcellular Localization Cytoplasm.
Disease Associations Blau syndrome (BS) [MIM:186580]: Rare autosomal dominant disorder characterized by early-onset granulomatous arthritis, uveitis and skin rash. {ECO:0000269PubMed:11528384, ECO:0000269PubMed:15812565, ECO:0000269PubMed:19169908, ECO:0000269PubMed:20199415}. Note=The disease is caused by mutations affecting the gene represented in this entry.Inflammatory bowel disease 1 (IBD1) [MIM:266600]: A chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology. It is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may affect any part of the gastrointestinal tract from the mouth to the anus, but most frequently it involves the terminal ileum and colon. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints. {ECO:0000269PubMed:11385576}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.Sarcoidosis early-onset (EOS) [MIM:609464]: A form of sarcoidosis manifesting in children younger than 4 years of age. Sarcoidosis is an idiopathic, systemic, inflammatory disease characterized by the formation of immune granulomas in involved organs. Granulomas predominantly invade the lungs and the lymphatic system, but also skin, liver, spleen, eyes and other organs may be involved. Early-onset sarcoidosis is quite rare and has a distinct triad of skin, joint and eye disorders, without apparent pulmonary involvement. Compared with an asymptomatic and sometimes naturally disappearing course of the disease in older children, early-onset sarcoidosis is progressive and in many cases causes severe complications, such as blindness, joint destruction and visceral involvement. {ECO:0000269PubMed:15459013}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Tissue Specificity Monocytes-specific.
Number of Interactions This gene and/or its encoded proteins are associated with 86 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.
Experimentally validated
Total 86 [view]
Protein-Protein 83 [view]
Protein-DNA 3 [view]
Protein-RNA 0
Predicted by orthology
Total 5 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0019899 enzyme binding
GO:0019901 protein kinase binding
GO:0032500 muramyl dipeptide binding
GO:0042834 peptidoglycan binding
GO:0050700 CARD domain binding
Biological Process
GO:0000187 activation of MAPK activity
GO:0002224 toll-like receptor signaling pathway
GO:0002227 innate immune response in mucosa
GO:0002253 activation of immune response
GO:0002367 cytokine production involved in immune response
GO:0002381 immunoglobulin production involved in immunoglobulin mediated immune response
GO:0002606 positive regulation of dendritic cell antigen processing and presentation
GO:0002710 negative regulation of T cell mediated immunity
GO:0002732 positive regulation of dendritic cell cytokine production
GO:0002755 MyD88-dependent toll-like receptor signaling pathway
GO:0002756 MyD88-independent toll-like receptor signaling pathway
GO:0002830 positive regulation of type 2 immune response
GO:0002862 negative regulation of inflammatory response to antigenic stimulus
GO:0002925 positive regulation of humoral immune response mediated by circulating immunoglobulin
GO:0006952 defense response
GO:0006963 positive regulation of antibacterial peptide biosynthetic process
GO:0006965 positive regulation of biosynthetic process of antibacterial peptides active against Gram-positive bacteria
GO:0007254 JNK cascade
GO:0007584 response to nutrient
GO:0008284 positive regulation of cell proliferation
GO:0009595 detection of biotic stimulus
GO:0016045 detection of bacterium
GO:0030277 maintenance of gastrointestinal epithelium
GO:0031398 positive regulation of protein ubiquitination
GO:0032088 negative regulation of NF-kappaB transcription factor activity
GO:0032494 response to peptidoglycan
GO:0032495 response to muramyl dipeptide
GO:0032496 response to lipopolysaccharide
GO:0032498 detection of muramyl dipeptide
GO:0032689 negative regulation of interferon-gamma production
GO:0032695 negative regulation of interleukin-12 production
GO:0032701 negative regulation of interleukin-18 production
GO:0032703 negative regulation of interleukin-2 production
GO:0032720 negative regulation of tumor necrosis factor production
GO:0032731 positive regulation of interleukin-1 beta production
GO:0032733 positive regulation of interleukin-10 production
GO:0032735 positive regulation of interleukin-12 production
GO:0032740 positive regulation of interleukin-17 production
GO:0032755 positive regulation of interleukin-6 production
GO:0032760 positive regulation of tumor necrosis factor production
GO:0032874 positive regulation of stress-activated MAPK cascade
GO:0034134 toll-like receptor 2 signaling pathway
GO:0034136 negative regulation of toll-like receptor 2 signaling pathway
GO:0034138 toll-like receptor 3 signaling pathway
GO:0034142 toll-like receptor 4 signaling pathway
GO:0034146 toll-like receptor 5 signaling pathway
GO:0034162 toll-like receptor 9 signaling pathway
GO:0034166 toll-like receptor 10 signaling pathway
GO:0035419 activation of MAPK activity involved in innate immune response
GO:0035556 intracellular signal transduction
GO:0035666 TRIF-dependent toll-like receptor signaling pathway
GO:0035872 nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
GO:0038123 toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124 toll-like receptor TLR6:TLR2 signaling pathway
GO:0042742 defense response to bacterium
GO:0042981 regulation of apoptotic process
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043330 response to exogenous dsRNA
GO:0043410 positive regulation of MAPK cascade
GO:0043552 positive regulation of phosphatidylinositol 3-kinase activity
GO:0044130 negative regulation of growth of symbiont in host
GO:0045087 innate immune response (InnateDB)
GO:0045089 positive regulation of innate immune response
GO:0045747 positive regulation of Notch signaling pathway
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0046330 positive regulation of JNK cascade
GO:0046645 positive regulation of gamma-delta T cell activation
GO:0050679 positive regulation of epithelial cell proliferation
GO:0050718 positive regulation of interleukin-1 beta secretion
GO:0050727 regulation of inflammatory response
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
GO:0050766 positive regulation of phagocytosis
GO:0050830 defense response to Gram-positive bacterium
GO:0050871 positive regulation of B cell activation
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051259 protein oligomerization
GO:0051353 positive regulation of oxidoreductase activity
GO:0051403 stress-activated MAPK cascade
GO:0051770 positive regulation of nitric-oxide synthase biosynthetic process
GO:0060585 positive regulation of prostaglandin-endoperoxide synthase activity
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0070423 nucleotide-binding oligomerization domain containing signaling pathway
GO:0070431 nucleotide-binding oligomerization domain containing 2 signaling pathway
GO:0071224 cellular response to peptidoglycan
GO:0071225 cellular response to muramyl dipeptide
GO:0071407 cellular response to organic cyclic compound
GO:0071608 macrophage inflammatory protein-1 alpha production
GO:0090022 regulation of neutrophil chemotaxis
GO:2000110 negative regulation of macrophage apoptotic process
GO:2000363 positive regulation of prostaglandin-E synthase activity
Cellular Component
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0005886 plasma membrane
GO:0008180 COP9 signalosome
GO:0009986 cell surface
GO:0031982 vesicle
GO:0043234 protein complex
Protein Structure and Domains
InterPro IPR001315 CARD domain
IPR003590 Leucine-rich repeat, ribonuclease inhibitor subtype
IPR007111 NACHT nucleoside triphosphatase
IPR011029 Death-like domain
IPR027417 P-loop containing nucleoside triphosphate hydrolase
PFAM PF00619
Post-translational Modifications
SwissProt Q9HC29
PhosphoSite PhosphoSite-Q9HC29
UniProt Splice Variant
Entrez Gene 64127
UniGene Hs.592072
RefSeq NP_071445
OMIM 605956
HPRD 05810
EMBL AB542700 AB542701 AC007608 AC007728 AF178930 AF385085 AF385087 AF385089 AF385090 AJ303140 AY423901 DQ868973 DQ869189 EF364441 EF624393 EF624394 EU817180 EU888272 EU888273 EU888274 EU888275 FN651786 HQ204571
GenPept AAG33677 AAK70863 AAK70865 AAK70867 AAK70868 AAQ93806 ABI96990 ABJ16061 ABN42698 ABS17611 ABS17612 ACF33179 ACF95817 ACF95818 ACF95819 ACF95820 ADN95581 BAJ13469 BAJ13470 CAC42117 CBJ18719