NOD2

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. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

Nucleotide Binding Oligomerization Domain Containing 2

Pattern recognition receptor (PRR) that detects bacterial peptidoglycan fragments and other danger signals and plays an important role in gastrointestinal immunity (PubMed:12527755).
Upon stimulation by muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, binds the proximal adapter receptor-interacting RIPK2, which recruits ubiquitin ligases as XIAP, BIRC2, BIRC3, INAVA and the LUBAC complex, triggering activation of MAP kinases and activation of NF-kappa-B signaling (PubMed:11087742, PubMed:21887730).
This in turn leads to the transcriptional activation of hundreds of genes involved in immune response. Required for MDP-induced NLRP1-dependent CASP1 activation and IL1B release in macrophages (PubMed:18511561).
Component of an autophagy-mediated antibacterial pathway together with ATG16L1 (PubMed:20637199).
Plays also a role in sensing single-stranded RNA (ssRNA) from viruses. Interacts with mitochondrial antiviral signaling/MAVS, leading to activation of interferon regulatory factor-3/IRF3 and expression of type I interferon (PubMed:19701189).
Besides recognizing pathogens, participates in surveillance of cellular homeostasis through sensing and binding to the cytosolic metabolite sphingosine-1-phosphate and then initating inflammation process (PubMed:33942347).

Activation of immune responseIEA:Ensembl
Cellular response to lipopolysaccharideManual Assertion Based On ExperimentIMP:UniProtKB
Cellular response to muramyl dipeptideManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to organic cyclic compoundIEA:Ensembl
Cellular response to peptidoglycanIEA:Ensembl
Defense responseManual Assertion Based On ExperimentTAS:HGNC-UCL
Defense response to bacteriumManual Assertion Based On ExperimentIDA:HGNC-UCL
Defense response to Gram-positive bacteriumIEA:Ensembl
Detection of bacteriumManual Assertion Based On ExperimentIDA:HGNC-UCL
Detection of biotic stimulusManual Assertion Based On ExperimentTAS:HGNC-UCL
Detection of muramyl dipeptideManual Assertion Based On ExperimentIDA:HGNC-UCL
Innate immune responseManual Assertion Based On ExperimentIDA:UniProtKB
Innate immune response in mucosaIEA:Ensembl
Intracellular signal transductionManual Assertion Based On ExperimentIDA:HGNC-UCL
Maintenance of gastrointestinal epitheliumManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of inflammatory response to antigenic stimulusIEA:Ensembl
Negative regulation of interferon-gamma productionIEA:Ensembl
Negative regulation of interleukin-12 productionIEA:Ensembl
Negative regulation of interleukin-18 productionIEA:Ensembl
Negative regulation of interleukin-2 productionIEA:Ensembl
Negative regulation of macrophage apoptotic processISS:BHF-UCL
Negative regulation of NF-kappaB transcription factor activityIEA:Ensembl
Negative regulation of T cell mediated immunityIEA:Ensembl
Negative regulation of toll-like receptor 2 signaling pathwayIEA:Ensembl
Negative regulation of tumor necrosis factor productionIEA:Ensembl
Nucleotide-binding oligomerization domain containing 2 signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Pattern recognition receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of B cell activationManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of biosynthetic process of antibacterial peptides active against Gram-positive bacteriaIEA:Ensembl
Positive regulation of cytokine production involved in immune responseManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of cytokine production involved in inflammatory responseManual Assertion Based On ExperimentIDA:CACAO
Positive regulation of dendritic cell antigen processing and presentationISS:BHF-UCL
Positive regulation of dendritic cell cytokine productionIEA:Ensembl
Positive regulation of epithelial cell proliferationISS:BHF-UCL
Positive regulation of ERK1 and ERK2 cascadeISS:BHF-UCL
Positive regulation of gamma-delta T cell activationISS:BHF-UCL
Positive regulation of humoral immune response mediated by circulating immunoglobulinIEA:Ensembl
Positive regulation of I-kappaB kinase/NF-kappaB signalingManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of innate immune responseIEA:Ensembl
Positive regulation of interleukin-1 beta productionManual Assertion Based On ExperimentIDA:HGNC-UCL
Positive regulation of interleukin-10 productionISS:BHF-UCL
Positive regulation of interleukin-12 productionIEA:Ensembl
Positive regulation of interleukin-17 productionManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of interleukin-6 productionManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of interleukin-8 productionManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of JNK cascadeManual Assertion Based On ExperimentIDA:MGI
Positive regulation of MAP kinase activityISS:BHF-UCL
Positive regulation of monocyte chemotactic protein-1 productionIEA:Ensembl
Positive regulation of NF-kappaB transcription factor activityManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of NIK/NF-kappaB signalingManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of nitric-oxide synthase biosynthetic processISS:BHF-UCL
Positive regulation of Notch signaling pathwayISS:BHF-UCL
Positive regulation of oxidoreductase activityISS:BHF-UCL
Positive regulation of peptidyl-tyrosine phosphorylationIEA:Ensembl
Positive regulation of phagocytosisIEA:Ensembl
Positive regulation of phosphatidylinositol 3-kinase activityISS:BHF-UCL
Positive regulation of prostaglandin-E synthase activityISS:BHF-UCL
Positive regulation of prostaglandin-endoperoxide synthase activityISS:BHF-UCL
Positive regulation of protein K63-linked ubiquitinationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of stress-activated MAPK cascadeManual Assertion Based On ExperimentIDA:MGI
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of tumor necrosis factor productionManual Assertion Based On ExperimentIDA:MGI
Positive regulation of type 2 immune responseManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of xenophagyIEA:Ensembl
Regulation of inflammatory response1 PublicationIC:BHF-UCL
Regulation of neutrophil chemotaxisIEA:Ensembl
Response to exogenous dsRNAIEA:Ensembl
Response to muramyl dipeptideManual Assertion Based On ExperimentIDA:HGNC-UCL
Response to nutrientIEA:Ensembl

Cell membrane
Cytoplasm
Membrane
Mitochondrion
Basolateral cell membrane

Blau syndrome (BLAUS):
An autosomal dominant inflammatory disorder characterized by the formation of immune granulomas invading the skin, joints and eye. Other organs may be involved. Clinical manifestations are variable and include early-onset granulomatous arthritis, uveitis and skin rash. Blindness, joint destruction and visceral involvement have been reported in severe cases.
Inflammatory bowel disease 1 (IBD1):
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.
Yao syndrome (YAOS):
An autoinflammatory disease characterized by periodic fever, dermatitis, polyarthritis, leg swelling, and gastrointestinal and sicca-like symptoms. YAOS is a complex disease with multifactorial inheritance.

Palmitoylated. Palmitoylation is required for proper recruitment to the bacterial entry site and hence for proper signaling upon cognate peptidoglycan detection.
Polyubiquitinated following MDP stimulation, leading to proteasome-mediated degradation (PubMed:23019338).