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用途:
For Research Use Only. Not for use in diagnostic or therapeutic procedures.
Involved in gastrointestinal immunity. 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. 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. Component of an autophagy-mediated antibacterial pathway together with ATG16L1. 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.
基因功能參考文獻(xiàn):
NOD2 is a target gene of miR-320 and is regulated by XIST. PMID: 29902461
The CTLA-4 gene +49 A/G polymorphism and the NOD2/CARD15 gene N852S polymorphism were not associated with CD or UC in a Turkish population PMID: 30213296
genetic deficiency of NOD2 plays a protective role during Aspergillus infection. PMID: 29980664
Results show that homozygotes carrying 3020insC gene mutations in NOD2 represent a high risk group for Crohn Disease. PMID: 29358789
Combination of polymorphisms in the NOD2, IL17RA, EPHA2 and KALRN genes could play a significant role in the development of sarcoidosis by maintaining a chronic pro-inflammatory status in macrophages PMID: 29554915
NOD2 mutation is associated with inflammatory bowel disease. PMID: 30167848
Overexpression of either NOD1 or NOD2 reduces cell proliferation and increases clonogenic potential in vitro in breast cancer cell lines. PMID: 29615116
To expand the computational strategy designed when studying XIAP, we have applied the molecular modeling tools to a list of 140 variants seen in CFTR associated with cystic fibrosis, and a list of undiagnosed variants in 17 different genes. Graphical abstract XIAP in Caspase 3 and NOD2 signaling pathways. PMID: 28204942
DNA sequencing revealed a previously unreported heterozygous mutation consisting of a G>A transition in exon 4 of the NOD2 gene. This resulted in a glutamic acid to lysine substitution in helical domain 2 of the nucleotide binding and oligomerization (NACHT) region, possibly reducing efficiency of auto-inhibition in NOD2 signaling. PMID: 27625029
The E600A mutation in the NOD2 gene may confer a higher penetrance of uveitis but a later onset of milder forms of non-ocular involvement. PMID: 27419275
the rarity and lack of association between common NOD2 mutations with IBD in our study seem to reveal a genetic characteristic of the population in our region. PMID: 29055077
novel mechanisms allowing Leptospira interrogans to escape recognition by the NOD1 and NOD2 receptors may be important in circumventing innate host responses PMID: 29211798
Studies results provide evidence that Crohn's disease patients have an impairment in mannose-binding lectin-mannose-associated serine protease functional activity and that this defect is associated with mannose-binding lectin 2 and NOD2 variants. PMID: 27404661
blockage of RhoA/ROCK repressed the TAK1/NOD2-mediated NF-kappaB pathway in HaCaT cells exposed to UVB. PMID: 28608226
this study reports the phenotype of a kindred with Blau syndrome caused by a novel NOD2 mutation PMID: 28836875
Results demonstrate that NOD2 contributes to the regulation of blood monocytes. PMID: 28834747
The interplay between NOD2 signaling, proinflammatory cytokines, CHIT1 activity, heightened oxidative stress and DNA damage orchestrates allergic airway inflammation and thus contributing to the pathogenesis of atopic asthma. PMID: 29572197
The changes in the nucleotide-binding oligomerization domain-like receptors (NLRs) in human corneas with disease expression may reflect different susceptibility to infectious and non-infectious injuries in corneas with various diseases. PMID: 26902715
The negative NOD2-smoking interaction in Crohn's disease is specific to the 1007fs variant. However, opposing rates of this variant and smoking across age at diagnosis may explain this negative interaction. PMID: 28668336
NOD2 up-regulates TLR2-mediated IL-23p19 expression via increasing c-Rel activation in Paneth cell-like cells PMID: 27563808
Results demonstrate the leucine-rich repeat (LRR) domain of Nod2 is sufficient to bind to bacterial peptidoglycan fragments and defined critical residues on Nod2 responsible for recognition. PMID: 27748583
Our findings suggest that genetic variants in NOD2 are only associated with OFG in patients with concurrent intestinal disease. PMID: 27306066
skin rash with granuloma formation and specific NOD2 mutations may represent early diagnostic hallmarks of EOS in infants with persistent inflammation. PMID: 28130683
The results confirmed that polymorphisms in NOD2 (Leu1007insC) and IRGM genes are associated with increased risk of Crohn's disease; whereas the ORMDL3 variant is associated with susceptibility to ulcerative colitis in the Lithuanian early-onset inflammatory bowel disease population. PMID: 27932194
We found that D299G and T399I SNPs were associated with Crohn's Disease susceptibility in patients carrying NOD2 variants. The patients carrying any mutant TLR4 variant were predisposed to develop a stricturing disease, especially in the presence of NOD2 mutation. PMID: 27290609
Homology modeling shows how the R702W mutation in NOD2 found in Crohn's disease, lowers the muramyl dipeptide-dependent activity of NOD2, and suggests that the residue is involved in autoregulation through direct interaction with the leucine rich domain. PMID: 27791288
wild type NOD2 is involved in preserving intestinal barrier integrity and immune homeostasis, properly functioning autophagy and balancing the gut microbiota composition; there is a high prevalence and effect size of NOD2 risk alleles in patients with Crohn's disease PMID: 29096557
NOD2 is an important mediator in the viral uptake and inflammatory response during the pathogenesis of CVB3 myocarditis. PMID: 28912259
We identified 2 missense mutations at 16q12 in NOD2 (p.Ala110Thr and p.Arg311Trp), which encodes nucleotide-binding oligomerization domain protein 2. We further examined 94 genetically unrelated AgP patients by targeted sequencing of NOD2 and found that 2 patients among them also carried the p.Arg311Trp variant. Furthermore, we found 3 additional missense mutations in this gene (p.His370Tyr, p.Arg459Cys, and p.Ala868Thr) PMID: 28682159
Performed genetic analysis in patients with Crohn's disease (CD) to determine effect of NOD2/CARD15 polymorphisms on treatment response to adalimumab and infliximab. PMID: 27533749
The study of the correlation between genotype and phenotypic expression showed that CARD15 mutation is associated with ileocecal Crohn's disease, with fistulizing and stenosing behavior in Crohn's disease as well as with severe evolution PMID: 28819537
Ligand-driven triggering of TLR-3, -4, NOD2, and DC-SIGN, despite reducing viral replication, markedly increased the capacity of infected dendritic cells to stimulate HIV-specific cytotoxic T-cells. PMID: 28266028
This work suggests that Crohn's Disease-associated Nod2 variants could be stabilized in vivo with a molecular chaperone. PMID: 28792733
From the results, the authors conclude that SNPs at the NOD2 and IL6 genes are associated with leprosy reactions as an outcome. PMID: 28715406
Based on molecular docking studies using PG ligands, we propose few residues - G825, D826 and N850 in hNOD1-LRR and L904, G905, W931, L932 and S933 in hNOD2-LRR, evolutionarily conserved across different host species, which may play a major role in ligand recognition. PMID: 28673961
NOD2 rs3135500 and IL12B rs1368439 SNPs were not genetic risk factors for colorectal cancer in the studied Iranian population. PMID: 27426943
Variants of NOD2/CARD15 and TLR4 do not confer susceptibility to inflammatory bowel disease, but appear to determine Crohn's disease phenotypes in this southeastern Brazilian population. PMID: 27107867
IFNgamma positively affects NOD2-mediated signaling in human conventional dendritic cells, in a manner considerably dependent on XIAP and partially dependent on mTOR. PMID: 26521691
The role of the NOD2 risk variants in bacterial translocation and spontaneous bacterial peritonitis is reported. PMID: 26725065
This study provides the evidence of NOD2/TLR2-mediated exacerbation of Atopic dermatitis through activation of innate immune cells. PMID: 26388234
NOD2 interactome and signaling depend upon the NOD2 mutation profile in CD PMID: 27812135
this study shows that NOD2 is upregulated in asthma patient tissues and cell lines, and that overexpression of NOD2 promotes cell proliferation and migration in airway smooth muscle cells PMID: 27889082
results indicate that NOD2 has a regulatory role in EndMT via activation of MEK/ERK in high glucose-treated GEnCs. Targeting this pathway is a promising strategy for intervention of DN endothelial dysfunction PMID: 28137583
A novel association between the NOD2 allele and an increased risk of postoperative intraabdominal infectious complications was observed in patients with Crohn's disease. PMID: 26946932
results of this work support the role of XIAP in mediating NOD2 signaling while reconciling the role of X-linked lymphoproliferative syndrome 2 and very-early-onset inflammatory bowel disease XIAP mutations in inflammatory cell death and provide a set of tools and framework to rapidly test newly discovered XIAP variants. PMID: 28404814
Cytokine production induced by invasive S. mutans via intracellular TLR2 and NOD2 in HAECs may be associated with inflammation. PMID: 27004566
bactDNA translocation is an independent risk factor of relapse in the short term in CD patients in remission. The increased inflammatory response to bactDNA translocation, particularly compromised in patients with a variant NOD2 genotype, is likely identifying a subgroup of CD patients susceptible of more aggressive early therapeutic approaches. PMID: 26902226
the results suggest that the chronic activation of NOD1 and NOD2 receptors might play a role in the development of gastric cancer. PMID: 27917621
this study reveals that LRRK2 is a new positive regulator of Rip2 and promotes inflammatory cytokine induction through the Nod1/2-Rip2 pathway. PMID: 27830463
Together, the data demonstrate that the NOD2-RIP2 pathway is activated in murine and human visceral leishmaniasis and plays a role in shaping adaptive immunity toward a Th1 profile. PMID: 27651416