Mus musculus Gene: Nod2
Summary
InnateDB Gene IDBG-67428.1
Last Modified 2018-06-05 [Report errors or provide feedback]
Gene Symbol Nod2
Gene Name Nucleotide-binding oligomerization domain-containing protein 2
Synonyms
Species Mus musculus
Ensembl Gene ENSMUSG00000055994
Encoded Proteins
Nucleotide-binding oligomerization domain-containing protein 2
Nucleotide-binding oligomerization domain-containing protein 2
Nucleotide-binding oligomerization domain-containing protein 2
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
Nod2-deficient mice have impaired resistance to Mycobacterium tuberculosis infection through defective innate and adaptive immunity.
Nod2 functions in non-hematopoietic cells of the small intestinal crypts and this is critical for protecting mice from a Th1-driven granulomatous inflammation in the ilum.
Nod2 and Nod1 account for neutrophil recruitment to the lungs of mice infected with Legionella pneumophila.
Nod2 and Nod1 activation results in substantial secretion of Ccl5 by murine macrophages and induces binding of NF-kappaB subunits to Ccl5 promoter.
Nod2 and Nod1 can detect Legionella pneumophila and these receptors modulate the in vivo pulmonary immune response differently.
Nod2 is both a positive and negative regulator of Tlr4 - the effect it exerts is dependent on the presence of MDP. Nod2 upon engagement with its ligand, MDP, positively regulates Tlr4-mediated signaling; in the absence of MDP, Nod2 negatively regulates the Tlr4 pathway.
Nod2 is a peripheral peptidoglycan intracellular sensor and is important for the progression and pathogenesis of experimental autoimmune encephalomyelitis (animal model of multiple sclerosis).
Nod2 detects heat-killed Legionella pneumophila and stimulates NFkB and IFN-beta promoter activity. Nod2 deficiency results in increased proinflammatory cytokine expression at 4hrs and greater neutrophil recruitment to the lung.
Ddx58 and Nod2 colocalize to cellular ruffles and cell-cell junctions to form a protein complex via the CARD domains. Ddx58 negatively regulates ligand-induced NFkB signalling mediated by Nod2, and conversely, Nod2 negatively regulates type I interferon induction by Ddx58. (Demonstrated in human)
Nod2 recognition of muramyl dipeptide, a component of bacterial cell walls, improves the barrier function of intestinal epithelial cells.
Nod2 enhances the innate immune response of alveolar macrophages to Mycobacterium tuberculosis in human. (Demonstrated in human)
Nod1 and Nod2 synergize with Tlr4 in dendritic cells to increase IL12 production and enhance invariant natural killer T (iNKT) cell activation, and are important regulators of the IFN gamma response by iNKT cells during S. typhimurium and L. monocytogenes infections.
Salmonella enterica serovar Typhimurium ?msbB that possesses a modified lipid A triggers exacerbated colitis in the absence of Nod1 and/or Nod2, which is likely due to increased Tlr2 stimulation.
Nod2 regulates type-1 cytokine responses to Mycobacterium avium but is not required for the control of M. avium infection in vivo.
Leukotriene B4 acts on Nod2 pathway to enhance the immune response against influenza A infection.
Entrez Gene
Summary Currently no Entrez Summary Available. You might want to check the Summary Sections of the Orthologs.
Gene Information
Type Protein coding
Genomic Location Chromosome 8:88647315-88688474
Strand Forward strand
Band C3
Transcripts
ENSMUST00000054324 ENSMUSP00000050538
ENSMUST00000109634 ENSMUSP00000105262
ENSMUST00000118370 ENSMUSP00000113773
ENSMUST00000124091
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 9 experimentally validated interaction(s) in this database.
They are also associated with 54 interaction(s) predicted by orthology.
Experimentally validated
Total 9 [view]
Protein-Protein 9 [view]
Protein-DNA 0
Protein-RNA 0
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 54 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0000166 nucleotide binding
GO:0003779 actin binding
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016888 endodeoxyribonuclease activity, producing 5'-phosphomonoesters
GO:0019899 enzyme binding
GO:0019901 protein kinase binding
GO:0030544 Hsp70 protein binding
GO:0032500 muramyl dipeptide binding
GO:0042834 peptidoglycan binding
GO:0050700 CARD domain binding
GO:0051879 Hsp90 protein binding
Biological Process
GO:0002227 innate immune response in mucosa
GO:0002253 activation of immune response
GO:0002367 cytokine production involved in immune response
GO:0002374 cytokine secretion involved in immune response
GO:0002376 immune system process
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: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:0006259 DNA metabolic process
GO:0006952 defense response
GO:0006954 inflammatory 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:0007165 signal transduction
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:0032757 positive regulation of interleukin-8 production
GO:0032760 positive regulation of tumor necrosis factor production
GO:0032874 positive regulation of stress-activated MAPK cascade
GO:0034136 negative regulation of toll-like receptor 2 signaling pathway
GO:0035556 intracellular signal transduction
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:0043406 positive regulation of MAP kinase activity
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: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: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: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:0071639 positive regulation of monocyte chemotactic protein-1 production
GO:0090022 regulation of neutrophil chemotaxis
GO:1900017 positive regulation of cytokine production involved in inflammatory response
GO:1901224 positive regulation of NIK/NF-kappaB signaling
GO:1902523 positive regulation of protein K63-linked ubiquitination
GO:1904417 positive regulation of xenophagy
GO:2000110 negative regulation of macrophage apoptotic process
GO:2000363 positive regulation of prostaglandin-E synthase activity
Cellular Component
GO:0005737 cytoplasm
GO:0005794 Golgi apparatus
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0005886 plasma membrane
GO:0008180 COP9 signalosome
GO:0009986 cell surface
GO:0016020 membrane
GO:0016323 basolateral plasma membrane
GO:0031982 vesicle
GO:0032991 macromolecular complex
Orthologs
No orthologs found for this gene
Pathways
NETPATH
REACTOME
Toll-Like Receptors Cascades pathway
Metabolism of proteins pathway
Deubiquitination pathway
Innate Immune System pathway
Toll Like Receptor 4 (TLR4) Cascade pathway
MAP kinase activation pathway
Toll Like Receptor TLR1:TLR2 Cascade pathway
Toll Like Receptor TLR6:TLR2 Cascade pathway
NOD1/2 Signaling Pathway pathway
activated TAK1 mediates p38 MAPK activation pathway
MyD88 dependent cascade initiated on endosome pathway
Ovarian tumor domain proteases pathway
Toll Like Receptor 7/8 (TLR7/8) Cascade pathway
Signaling by Interleukins pathway
MyD88 cascade initiated on plasma membrane pathway
Cytokine Signaling in Immune system pathway
Toll Like Receptor 2 (TLR2) Cascade pathway
Post-translational protein modification pathway
Toll Like Receptor 3 (TLR3) Cascade pathway
Interleukin-17 signaling pathway
Toll Like Receptor 9 (TLR9) Cascade pathway
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 pathway
Interleukin-1 signaling pathway
Immune System pathway
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways pathway
TAK1 activates NFkB by phosphorylation and activation of IKKs complex pathway
MyD88-independent TLR4 cascade pathway
Interleukin-1 family signaling pathway
Toll Like Receptor 5 (TLR5) Cascade pathway
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation pathway
MyD88:Mal cascade initiated on plasma membrane pathway
Toll Like Receptor 10 (TLR10) Cascade pathway
TRIF(TICAM1)-mediated TLR4 signaling pathway
KEGG
NOD-like receptor signaling pathway pathway
TNF signaling pathway pathway
Tuberculosis pathway
Inflammatory bowel disease (IBD) pathway
INOH
PID BIOCARTA
PID NCI
Cross-References
SwissProt Q8K3Z0
TrEMBL
UniProt Splice Variant
Entrez Gene 257632
UniGene
RefSeq XM_006531028 NM_145857 XM_006531029 XM_011248390
OMIM
CCDS CCDS52632
HPRD
IMGT
MGI ID MGI:2429397
MGI Symbol Nod2
EMBL AF520774 BC044774
GenPept AAH44774 AAM76073
RNA Seq Atlas 257632