InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: NOD2

Summary

InnateDB Protein

IDBP-30656.6

Last Modified

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

Gene Symbol

NOD2

Protein Name

nucleotide-binding oligomerization domain containing 2

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000300589

InnateDB Gene

IDBG-30654 (NOD2)

Protein Structure

UniProt Annotation

Function

Recognizes muramyl dipeptide (MDP) constituents of bacterial peptidoglycans and plays a key role in gastrointestinal immunity: upon stimulation, binds the proximal adapter receptor- interacting RIPK2, which recruits ubiquitin ligases as XIAP, BIRC2, BIRC3 and the LUBAC complex, triggering activation of MAP kinases and activation of NF-kappa-B signaling, leading to activate the transcription of hundreds of genes involved in immune response. {ECO:0000269PubMed:23806334}.

Subcellular Localization

Cytoplasm.

Disease Associations

Blau syndrome (BS) [MIM:186580]: Rare autosomal dominant disorder characterized by early-onset granulomatous arthritis, uveitis and skin rash. {ECO:0000269PubMed:11528384, ECO:0000269PubMed:15812565, ECO:0000269PubMed:19169908, ECO:0000269PubMed:20199415}. Note=The disease is caused by mutations affecting the gene represented in this entry.Inflammatory bowel disease 1 (IBD1) [MIM:266600]: A chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology. It is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may affect any part of the gastrointestinal tract from the mouth to the anus, but most frequently it involves the terminal ileum and colon. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints. {ECO:0000269PubMed:11385576}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.Sarcoidosis early-onset (EOS) [MIM:609464]: A form of sarcoidosis manifesting in children younger than 4 years of age. Sarcoidosis is an idiopathic, systemic, inflammatory disease characterized by the formation of immune granulomas in involved organs. Granulomas predominantly invade the lungs and the lymphatic system, but also skin, liver, spleen, eyes and other organs may be involved. Early-onset sarcoidosis is quite rare and has a distinct triad of skin, joint and eye disorders, without apparent pulmonary involvement. Compared with an asymptomatic and sometimes naturally disappearing course of the disease in older children, early-onset sarcoidosis is progressive and in many cases causes severe complications, such as blindness, joint destruction and visceral involvement. {ECO:0000269PubMed:15459013}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Monocytes-specific.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 86 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.

Experimentally validated
Total	86 [view]
Protein-Protein	83 [view]
Protein-DNA	3 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	5 [view]

Gene Ontology

Molecular Function

Accession	GO Term
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:0000187	activation of MAPK activity
GO:0002224	toll-like receptor signaling pathway
GO:0002227	innate immune response in mucosa
GO:0002253	activation of 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:0002755	MyD88-dependent toll-like receptor signaling pathway
GO:0002756	MyD88-independent toll-like receptor signaling pathway
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:0006963	positive regulation of antibacterial peptide biosynthetic process
GO:0006965	positive regulation of biosynthetic process of antibacterial peptides active against Gram-positive bacteria
GO:0007254	JNK cascade
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:0034134	toll-like receptor 2 signaling pathway
GO:0034136	negative regulation of toll-like receptor 2 signaling pathway
GO:0034138	toll-like receptor 3 signaling pathway
GO:0034142	toll-like receptor 4 signaling pathway
GO:0034146	toll-like receptor 5 signaling pathway
GO:0034162	toll-like receptor 9 signaling pathway
GO:0034166	toll-like receptor 10 signaling pathway
GO:0035419	activation of MAPK activity involved in innate immune response
GO:0035556	intracellular signal transduction
GO:0035666	TRIF-dependent toll-like receptor signaling pathway
GO:0035872	nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
GO:0038123	toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124	toll-like receptor TLR6:TLR2 signaling pathway
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: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:0051259	protein oligomerization
GO:0051353	positive regulation of oxidoreductase activity
GO:0051403	stress-activated MAPK cascade
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:0070423	nucleotide-binding oligomerization domain containing signaling pathway
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: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

Protein Structure and Domains

PDB ID

InterPro

IPR001315 CARD domain
IPR003590 Leucine-rich repeat, ribonuclease inhibitor subtype
IPR007111 NACHT nucleoside triphosphatase
IPR011029 Death-like domain
IPR027417 P-loop containing nucleoside triphosphate hydrolase

PFAM

PF00619

PRINTS

PIRSF

SMART

SM00114
SM00368

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q9HC29