Version 5.4
Bos taurus Gene: NOD2
Summary
InnateDB Gene IDBG-631640.3
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol NOD2
Gene Name Nucleotide-binding oligomerization domain-containing protein 2
Synonyms CARD15
Species Bos taurus
Ensembl Gene ENSBTAG00000020936
Encoded Proteins
IDBP-683198
Nucleotide-binding oligomerization domain-containing protein 2
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation from Orthologs
Summary
PMID 17690884
[Homo sapiens] NOD2 and NOD1 represent central players in the control of the immune responses to bacterial infections and inflammation.
PMID 18240302
[Homo sapiens] NOD2 is an intracellular receptor of muramyl dipeptide (MDP), a component of peptidoglycan present in the cell wall of Gram-positive (G+) and Gram-negative (G-) bacteria.
PMID 17705131
[Homo sapiens] NOD2 and NOD1 can induce CCL5 (RANTES) through NF-kappaB pathway, orchestrating the global Nod-dependent immune defence during bacterial infections.
PMID 19541630
[Homo sapiens] NOD2-dependent recognition of S. aureus and muramyl dipeptide is facilitated by alpha-toxin (alpha-hemolysin), a pore-forming toxin and virulence factor of the pathogen and is dependent on IL-1beta-amplified production of IL-6.
PMID 19898471
[Homo sapiens] NOD2 and NOD1 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry.
PMID 19966812
[Homo sapiens] NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation.
PMID 20200479
[Homo sapiens] NOD2 recruits the critical autophagy protein ATG16L1 to the plasma membrane during bacterial invasion.
PMID 19701189
[Homo sapiens] NOD2 functions as a cytoplasmic viral pattern-recognition receptor (PRR) and activates an innate immune responses to viral ssRNA by triggering activation of interferon-regulatory factor 3 (IRF3) and production of interferon-beta (IFNB1).
PMID 21199260
[Homo sapiens] 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 signalling; in the absence of MDP, NOD2 negatively regulates the TLR4 pathway. (Demonstrated in murine model)
PMID 21236705
[Homo sapiens] NOD2 is a peripheral peptidoglycan intracellular sensor and is important for the progression and pathogenesis of experimental autoimmune encephalomyelitis (animal model of multiple sclerosis).
PMID 21108472
[Homo sapiens] 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. (Demonstrated in murine model)
PMID 21690088
[Homo sapiens] 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.
PMID 22750073
[Homo sapiens] NOD2 recognition of muramyl dipeptide, a component of bacterial cell walls, improves the barrier function of intestinal epithelial cells. (Demonstrated in mice)
PMID 22531915
[Homo sapiens] NOD2 enhances the innate immune response of alveolar macrophages to Mycobacterium tuberculosis in human.
PMID 24670424
[Homo sapiens] Following NOD2 activation, IRF4 interacts with MYD88, TRAF6, and RIPK2 and downregulates K63-linked polyubiquitinylation of RICK and TRAF6 leading to disruption of NFkB activation pathways.
PMID 25433720
[Homo sapiens] NOD2 plays a role in intestinal innate immunity by regulating the expression of DEFA5 and DEFA6 through the NF-kB and MAPK pathways.
PMID 18981137
[Mus musculus] Nod2-deficient mice have impaired resistance to Mycobacterium tuberculosis infection through defective innate and adaptive immunity.
PMID 20679225
[Mus musculus] 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.
PMID 20685341
[Mus musculus] Nod2 and Nod1 account for neutrophil recruitment to the lungs of mice infected with Legionella pneumophila.
PMID 17705131
[Mus musculus] Nod2 and Nod1 activation results in substantial secretion of Ccl5 by murine macrophages and induces binding of NF-kappaB subunits to Ccl5 promoter.
PMID 21072876
[Mus musculus] Nod2 and Nod1 can detect Legionella pneumophila and these receptors modulate the in vivo pulmonary immune response differently.
PMID 21199260
[Mus musculus] 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.
PMID 21236705
[Mus musculus] Nod2 is a peripheral peptidoglycan intracellular sensor and is important for the progression and pathogenesis of experimental autoimmune encephalomyelitis (animal model of multiple sclerosis).
PMID 21108472
[Mus musculus] 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.
PMID 21690088
[Mus musculus] 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)
PMID 22750073
[Mus musculus] Nod2 recognition of muramyl dipeptide, a component of bacterial cell walls, improves the barrier function of intestinal epithelial cells.
PMID 22531915
[Mus musculus] Nod2 enhances the innate immune response of alveolar macrophages to Mycobacterium tuberculosis in human. (Demonstrated in human)
PMID 24163408
[Mus musculus] 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.
PMID 25423082
[Mus musculus] Salmonella enterica serovar Typhimurium Î?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.
PMID 25817335
[Mus musculus] Nod2 regulates type-1 cytokine responses to Mycobacterium avium but is not required for the control of M. avium infection in vivo.
PMID 26444420
[Mus musculus] Leukotriene B4 acts on Nod2 pathway to enhance the immune response against influenza A infection.
Entrez Gene
Summary This gene does not have any Entrez summary - the following is the summary from its human ortholog ENSG00000167207:
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. [provided by RefSeq, Jul 2008]
Gene Information
Type Protein coding
Genomic Location Chromosome 18:19181972-19212607
Strand Forward strand
Band
Transcripts
ENSBTAT00000027887 ENSBTAP00000027887
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 0 experimentally validated interaction(s) in this database.
They are also associated with 41 interaction(s) predicted by orthology.
Predicted by orthology
Total 41 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0000166 nucleotide binding
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:0002227 innate immune response in mucosa
GO:0002253 activation of immune response
GO:0002367 cytokine production 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: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:0006963 positive regulation of antibacterial peptide biosynthetic process
GO:0006965 positive regulation of biosynthetic process of antibacterial peptides active against Gram-positive bacteria
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:0034136 negative regulation of toll-like receptor 2 signaling pathway
GO:0035419 activation of MAPK activity involved in innate immune response
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: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
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: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: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:0005622 intracellular
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
Orthologs
Species
Homo sapiens
Mus musculus
Gene ID
Gene Order
ENSG00000167207
View Gene Order
ENSMUSG00000055994
View Gene Order
Pathways
NETPATH
REACTOME
REACT_224941
NOD1/2 Signaling Pathway pathway
REACT_218237
Toll Like Receptor 2 (TLR2) Cascade pathway
REACT_210286
TRIF-mediated TLR3/TLR4 signaling pathway
REACT_224703
Toll Like Receptor 3 (TLR3) Cascade pathway
REACT_205566
Activated TLR4 signalling pathway
REACT_222278
Toll Like Receptor 7/8 (TLR7/8) Cascade pathway
REACT_224546
MyD88-independent cascade pathway
REACT_207897
activated TAK1 mediates p38 MAPK activation pathway
REACT_217035
Toll Like Receptor 9 (TLR9) Cascade pathway
REACT_227345
MyD88:Mal cascade initiated on plasma membrane pathway
REACT_210224
Toll Like Receptor 5 (TLR5) Cascade pathway
REACT_213612
Cytokine Signaling in Immune system pathway
REACT_213138
Immune System pathway
REACT_227036
MAP kinase activation in TLR cascade pathway
REACT_211964
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 pathway
REACT_219220
Toll-Like Receptors Cascades pathway
REACT_219947
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways pathway
REACT_223848
Toll Like Receptor 10 (TLR10) Cascade pathway
REACT_225653
Toll Like Receptor TLR6:TLR2 Cascade pathway
REACT_218091
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation pathway
REACT_216676
Toll Like Receptor TLR1:TLR2 Cascade pathway
REACT_219586
MyD88 dependent cascade initiated on endosome pathway
REACT_217214
TAK1 activates NFkB by phosphorylation and activation of IKKs complex pathway
REACT_216714
Innate Immune System pathway
REACT_207826
Interleukin-1 signaling pathway
REACT_206833
Signaling by Interleukins pathway
REACT_211704
Toll Like Receptor 4 (TLR4) Cascade pathway
REACT_217527
MyD88 cascade initiated on plasma membrane pathway
KEGG
INOH
PID NCI
Pathway Predictions based on Human Orthology Data
NETPATH
REACTOME
REACT_21368
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 pathway
REACT_21399
activated TAK1 mediates p38 MAPK activation pathway
REACT_21281
TAK1 activates NFkB by phosphorylation and activation of IKKs complex pathway
REACT_6809
MyD88-independent cascade pathway
REACT_6783
Toll Like Receptor 3 (TLR3) Cascade pathway
REACT_6788
MyD88:Mal cascade initiated on plasma membrane pathway
REACT_8005
Toll Like Receptor TLR1:TLR2 Cascade pathway
REACT_8006
Toll Like Receptor TLR6:TLR2 Cascade pathway
REACT_25024
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation pathway
REACT_25222
MyD88 dependent cascade initiated on endosome pathway
REACT_9047
Toll Like Receptor 9 (TLR9) Cascade pathway
REACT_27215
MyD88 cascade initiated on plasma membrane pathway
REACT_9027
Toll Like Receptor 10 (TLR10) Cascade pathway
REACT_6894
Toll Like Receptor 4 (TLR4) Cascade pathway
REACT_9061
Toll Like Receptor 5 (TLR5) Cascade pathway
REACT_75776
NOD1/2 Signaling Pathway pathway
REACT_22442
Interleukin-1 signaling pathway
REACT_9020
Toll Like Receptor 7/8 (TLR7/8) Cascade pathway
REACT_75790
Cytokine Signaling in Immune system pathway
REACT_6802
Innate Immune System pathway
REACT_7980
Toll Like Receptor 2 (TLR2) Cascade pathway
REACT_6966
Toll-Like Receptors Cascades pathway
REACT_21308
MAP kinase activation in TLR cascade pathway
REACT_75913
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways pathway
REACT_6900
Immune System pathway
REACT_22232
Signaling by Interleukins pathway
REACT_6890
Activated TLR4 signalling pathway
REACT_25281
TRIF-mediated TLR3/TLR4 signaling pathway
REACT_263316
Toll Like Receptor 3 (TLR3) Cascade pathway
REACT_229712
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation pathway
REACT_263004
Toll Like Receptor 2 (TLR2) Cascade pathway
REACT_239142
Innate Immune System pathway
REACT_204812
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 pathway
REACT_245896
MyD88 cascade initiated on plasma membrane pathway
REACT_233584
Cytokine Signaling in Immune system pathway
REACT_255939
Toll Like Receptor TLR1:TLR2 Cascade pathway
REACT_262171
MAP kinase activation in TLR cascade pathway
REACT_230745
Immune System pathway
REACT_260773
Toll Like Receptor 5 (TLR5) Cascade pathway
REACT_254406
Toll Like Receptor TLR6:TLR2 Cascade pathway
REACT_237946
activated TAK1 mediates p38 MAPK activation pathway
REACT_249409
Toll Like Receptor 9 (TLR9) Cascade pathway
REACT_251547
Toll-Like Receptors Cascades pathway
REACT_261687
Signaling by Interleukins pathway
REACT_211125
NOD1/2 Signaling Pathway pathway
REACT_256727
MyD88 dependent cascade initiated on endosome pathway
REACT_206758
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways pathway
REACT_262462
Activated TLR4 signalling pathway
REACT_224208
Interleukin-1 signaling pathway
REACT_241786
MyD88-independent cascade pathway
REACT_242921
Toll Like Receptor 7/8 (TLR7/8) Cascade pathway
REACT_230045
MyD88:Mal cascade initiated on plasma membrane pathway
REACT_238546
TRIF-mediated TLR3/TLR4 signaling pathway
REACT_219800
TAK1 activates NFkB by phosphorylation and activation of IKKs complex pathway
REACT_261340
Toll Like Receptor 10 (TLR10) Cascade pathway
REACT_246719
Toll Like Receptor 4 (TLR4) Cascade pathway
KEGG
hsa04621
NOD-like receptor signaling pathway pathway
hsa05131
Shigellosis pathway
mmu04621
NOD-like receptor signaling pathway pathway
INOH
PID NCI
nfkappabcanonicalpathway
Canonical NF-kappaB pathway
Cross-References
SwissProt Q6E804
TrEMBL
UniProt Splice Variant
Entrez Gene 444867
UniGene Bt.30778
RefSeq NM_001002889 XM_005218467
HUGO
OMIM
CCDS
HPRD
IMGT
EMBL AY518737 AY518739 AY518740 AY518741 AY518742 AY518743 AY518744 AY518745 AY518746 AY518747 AY518748
GenPept AAS09824 AAS09826
RNA Seq Atlas 444867

If you use InnateDB for your research, please cite the following publication:

Breuer et al., InnateDB: systems biology of innate immunity and beyond - recent updates and continuing curation. Nucl. Acids Res. (2013) 41 (D1) 

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Funding is currently provided by Allergen and EMBL Australia. Previous funding has been provided by Genome Canada, the Foundation for the National Institutes of Health through the Grand Challenges in Global Health initiative and by Teagasc. InnateDB curated interactions are licensed under the Design Science License. All other data is licensed under the terms of the originating database. Contact: innatedb-mail@sfu.ca