Anti-CARD15/NOD2 antibody [EPR28206-156]

Target data

Pattern recognition receptor (PRR) that detects bacterial peptidoglycan fragments and other danger signals and plays an important role in gastrointestinal immunity (PubMed : 15692051, PubMed : 15692052, PubMed : 19805227, PubMed : 21715553). Specifically activated by muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan found in every bacterial peptidoglycan type (PubMed : 15692051, PubMed : 15692052, PubMed : 25429073). NOD2 specifically recognizes and binds 6-O-phospho-MDP, the phosphorylated form of MDP, which is generated by NAGK (PubMed : 36002575). 6-O-phospho-MDP-binding triggers oligomerization that facilitates the binding and subsequent activation of the proximal adapter receptor-interacting RIPK2 (PubMed : 15692051, PubMed : 15692052, PubMed : 22607974). Following recruitment, RIPK2 undergoes 'Met-1'- (linear) and 'Lys-63'-linked polyubiquitination by E3 ubiquitin-protein ligases XIAP, BIRC2, BIRC3 and the LUBAC complex, becoming a scaffolding protein for downstream effectors, triggering activation of the NF-kappa-B and MAP kinases signaling (PubMed : 15692051, PubMed : 15692052, PubMed : 22607974). This in turn leads to the transcriptional activation of hundreds of genes involved in immune response (PubMed : 22607974). Its ability to detect bacterial MDP plays a central role in maintaining the equilibrium between intestinal microbiota and host immune responses to control inflammation (PubMed : 19805227, PubMed : 21421666, PubMed : 23281400, PubMed : 24062413, PubMed : 24882705, PubMed : 25088769, PubMed : 25666722, PubMed : 28127403). An imbalance in this relationship results in dysbiosis, whereby pathogenic bacteria prevail on commensals, causing damage in the intestinal epithelial barrier as well as allowing bacterial invasion and inflammation (PubMed : 23281400, PubMed : 25088769). Acts as a regulator of appetite by sensing MDP in a subset of brain neurons : microbiota-derived MDP reach the brain, where they bind and activate NOD2 in inhibitory hypothalamic neurons, decreasing neuronal activity, thereby regulating satiety and body temperature (PubMed : 35420957). NOD2-dependent MDP-sensing of bacterial cell walls in the intestinal epithelial compartment contributes to sustained postnatal growth upon undernutrition (PubMed : 36821686). Also plays a role in antiviral response by acting as a sensor of single-stranded RNA (ssRNA) from viruses : upon ssRNA-binding, interacts with MAVS, leading to activation of interferon regulatory factor-3/IRF3 and expression of type I interferon (By similarity). Also acts as a regulator of autophagy in dendritic cells via its interaction with ATG16L1, possibly by recruiting ATG16L1 at the site of bacterial entry (PubMed : 19898471, PubMed : 19966812, PubMed : 27230380). NOD2 activation in the small intestine crypt also contributes to intestinal stem cells survival and function : acts by promoting mitophagy via its association with ATG16L1 (PubMed : 31919280). In addition to its main role in innate immunity, also regulates the adaptive immune system by acting as regulator of helper T-cell and regulatory T-cells (Tregs) (PubMed : 21856952, PubMed : 27230380). Besides recognizing pathogens, also involved in the endoplasmic reticulum stress response : acts by sensing and binding to the cytosolic metabolite sphingosine-1-phosphate generated in response to endoplasmic reticulum stress, initiating an inflammation process that leads to activation of the NF-kappa-B and MAP kinases signaling (PubMed : 27007849). May also be involved in NLRP1 activation following activation by MDP, leading to CASP1 activation and IL1B release in macrophages (PubMed : 18511561).