InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Gene: Nod2

Summary

InnateDB Gene

IDBG-179050.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Nod2

Gene Name

nucleotide-binding oligomerization domain containing 2

Synonyms

Species

Mus musculus

Ensembl Gene

ENSMUSG00000055994

Encoded Proteins

IDBP-179052

nucleotide-binding oligomerization domain containing 2

IDBP-261977

nucleotide-binding oligomerization domain containing 2

IDBP-400810

nucleotide-binding oligomerization domain containing 2

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 18981137

Nod2-deficient mice have impaired resistance to Mycobacterium tuberculosis infection through defective innate and adaptive immunity.

PMID 20679225

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

Nod2 and Nod1 account for neutrophil recruitment to the lungs of mice infected with Legionella pneumophila.

PMID 17705131

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

Nod2 and Nod1 can detect Legionella pneumophila and these receptors modulate the in vivo pulmonary immune response differently.

PMID 21199260

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

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

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

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

Nod2 recognition of muramyl dipeptide, a component of bacterial cell walls, improves the barrier function of intestinal epithelial cells.

PMID 22531915

Nod2 enhances the innate immune response of alveolar macrophages to Mycobacterium tuberculosis in human. (Demonstrated in human)

PMID 24163408

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

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.

PMID 25817335

Nod2 regulates type-1 cytokine responses to Mycobacterium avium but is not required for the control of M. avium infection in vivo.

PMID 26444420

Leukotriene B4 acts on Nod2 pathway to enhance the immune response against influenza A infection.

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.

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 8:88647315-88688474

Strand

Forward strand

Band

Transcripts

ENSMUST00000054324	ENSMUSP00000050538
ENSMUST00000109634	ENSMUSP00000105262
ENSMUST00000118370	ENSMUSP00000113773
ENSMUST00000124091

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 8 experimentally validated interaction(s) in this database.
They are also associated with 46 interaction(s) predicted by orthology.

Experimentally validated
Total	8 [view]
Protein-Protein	8 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	46 [view]

Gene Ontology

Molecular Function

Accession	GO Term
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:0032500	muramyl dipeptide binding
GO:0042834	peptidoglycan binding
GO:0050700	CARD domain binding

Biological Process

GO:0000737	DNA catabolic process, endonucleolytic
GO:0002227	innate immune response in mucosa
GO:0002253	activation of immune response
GO:0002282	microglial cell activation involved in immune response
GO:0002367	cytokine production involved in immune response
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: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: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 (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:0052033	pathogen-associated molecular pattern dependent induction by symbiont of host innate immune response
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: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

Bos taurus

Gene ID

Gene Order

ENSG00000167207

View Gene Order

ENSBTAG00000020936

Not yet available

Pathways

NETPATH

REACTOME

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

mmu04621

NOD-like receptor signaling pathway pathway

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_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

hsa04621

NOD-like receptor signaling pathway pathway

hsa05131

Shigellosis pathway

INOH

PID NCI

nfkappabcanonicalpathway

Canonical NF-kappaB pathway

Cross-References

SwissProt

Q8K3Z0

TrEMBL

Q2PZA3 Q3V2V8 Q80SY9

UniProt Splice Variant

Entrez Gene

257632

UniGene

Mm.222633

RefSeq

NM_145857 XM_006531027 XM_006531028 XM_006531029

OMIM

CCDS

CCDS52632

HPRD

IMGT

MGI ID

MGI:2429397

MGI Symbol

Nod2

EMBL

AC156937 AF520774 AK089390 AY160220 AY160340 AY160341 AY160342 AY160343 AY160344 AY160345 AY160346 AY160347 AY160348 AY160360 AY160361 AY160362 AY160363 AY160364 AY160365 AY160366 AY160367 AY160368 AY160560 AY160561 AY160562 AY160563 AY160564 AY160565 AY160566 AY160567 AY160568 AY160570 AY160571 AY160572 AY160573 AY160574 AY160575 AY160576 AY160577 AY160578 AY160600 AY160601 AY160602 AY160603 AY160604 AY160605 AY160606 AY160607 AY160608 AY160610 AY160611 AY160612 AY160613 AY160614 AY160615 AY160616 AY160617 AY160618 AY160650 AY160651 AY160652 AY160653 AY160654 AY160655 AY160656 AY160657 AY160658 BC044774 DQ289012

GenPept

AAH44774 AAM76073 AAN52477 AAN57787 AAN57789 AAN62470 AAN62471 AAN63034 AAN63035 AAN63039 ABC25455 BAE43397

RNA Seq Atlas

257632