#ID(s) interactor A ID(s) interactor B Alt. ID(s) interactor A Alt. ID(s) interactor B Alias(es) interactor A Alias(es) interactor B Interaction detection method(s) Publication 1st author(s) Publication Identifier(s) Taxid interactor A Taxid interactor B Interaction type(s) Source database(s) Interaction identifier(s) Confidence value(s) Expansion method(s) Biological role(s) interactor A Biological role(s) interactor B Experimental role(s) interactor A Experimental role(s) interactor B Type(s) interactor A Type(s) interactor B Xref(s) interactor A Xref(s) interactor B Interaction Xref(s) Annotation(s) interactor A Annotation(s) interactor B Interaction annotation(s) Host organism(s) Interaction parameter(s) Creation date Update date Checksum(s) interactor A Checksum(s) interactor B Interaction Checksum(s) Negative Feature(s) interactor A Feature(s) interactor B Stoichiometry(s) interactor A Stoichiometry(s) interactor B Identification method participant A Identification method participant B uniprotkb:Q9HC29 uniprotkb:A2AIV8 intact:EBI-7445625|uniprotkb:Q96RH5|uniprotkb:Q96RH8|uniprotkb:Q96RH6|uniprotkb:E2JEQ6|intact:MINT-151071|ensembl:ENSP00000300589 intact:EBI-9549098|ensembl:ENSMUSP00000028294|ensembl:ENSMUSP00000097876 psi-mi:nod2_human(display_long)|uniprotkb:IBD1(gene name synonym)|uniprotkb:NOD2(gene name)|psi-mi:NOD2(display_short)|uniprotkb:CARD15(gene name synonym)|uniprotkb:Caspase recruitment domain-containing protein 15(gene name synonym)|uniprotkb:Inflammatory bowel disease protein 1(gene name synonym) psi-mi:card9_mouse(display_long)|uniprotkb:Card9(gene name)|psi-mi:Card9(display_short) psi-mi:"MI:0007"(anti tag coimmunoprecipitation) Parkhouse et al. (2014) pubmed:24960071|imex:IM-22927 taxid:9606(human)|taxid:9606(Homo sapiens) taxid:10090(mouse)|taxid:10090(Mus musculus) psi-mi:"MI:0915"(physical association) psi-mi:"MI:0471"(MINT) intact:EBI-9549096|imex:IM-22927-1 - - psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0499"(unspecified role) psi-mi:"MI:0496"(bait) psi-mi:"MI:0498"(prey) psi-mi:"MI:0326"(protein) psi-mi:"MI:0326"(protein) refseq:NP_071445.1|refseq:XP_005256141.1|ensembl:ENSG00000167207(gene)|ensembl:ENST00000300589(transcript)|go:"GO:0002221"(pattern recognition receptor signaling pathway)|go:"GO:0002227"(innate immune response in mucosa)|go:"GO:0002253"(activation of immune response)|go:"GO:0002606"(positive regulation of dendritic cell antigen processing and presentation)|go:"GO:0002710"(negative regulation of T cell mediated immunity)|go:"GO:0002720"(positive regulation of cytokine production involved in immune response)|go:"GO:0002732"(positive regulation of dendritic cell cytokine production)|go:"GO:0002830"(positive regulation of type 2 immune response)|go:"GO:0002862"(negative regulation of inflammatory response to antigenic stimulus)|go:"GO:0002925"(positive regulation of humoral immune response mediated by circulating immunoglobulin)|go:"GO:0003779"(actin binding)|go:"GO:0005524"(ATP binding)|go:"GO:0005737"(cytoplasm)|go:"GO:0005739"(mitochondrion)|go:"GO:0005794"(Golgi apparatus)|go:"GO:0005829"(cytosol)|go:"GO:0016045"(detection of bacterium)|go:"GO:0016323"(basolateral plasma membrane)|go:"GO:0019899"(enzyme binding)|go:"GO:0019901"(protein kinase binding)|go:"GO:0030277"(maintenance of gastrointestinal epithelium)|go:"GO:0030544"(Hsp70 protein binding)|go:"GO:0031982"(vesicle)|go:"GO:0032088"(negative regulation of NF-kappaB transcription factor activity)|go:"GO:0005856"(cytoskeleton)|go:"GO:0032495"(response to muramyl dipeptide)|go:"GO:0005886"(plasma membrane)|go:"GO:0032498"(detection of muramyl dipeptide)|go:"GO:0032500"(muramyl dipeptide binding)|go:"GO:0032689"(negative regulation of interferon-gamma production)|go:"GO:0032695"(negative regulation of interleukin-12 production)|go:"GO:0032701"(negative regulation of interleukin-18 production)|go:"GO:0032703"(negative regulation of interleukin-2 production)|go:"GO:0032720"(negative regulation of tumor necrosis factor production)|go:"GO:0032731"(positive regulation of interleukin-1 beta production)|go:"GO:0006952"(defense response)|go:"GO:0032733"(positive regulation of interleukin-10 production)|go:"GO:0032735"(positive regulation of interleukin-12 production)|go:"GO:0032740"(positive regulation of interleukin-17 production)|go:"GO:0032755"(positive regulation of interleukin-6 production)|go:"GO:0032757"(positive regulation of interleukin-8 production)|go:"GO:0006965"(positive regulation of biosynthetic process of antibacterial peptides active against Gram-positive bacteria)|go:"GO:0032760"(positive regulation of tumor necrosis factor production)|go:"GO:0032874"(positive regulation of stress-activated MAPK cascade)|go:"GO:0032991"(protein-containing complex)|go:"GO:0034136"(negative regulation of toll-like receptor 2 signaling pathway)|go:"GO:0035556"(intracellular signal transduction)|go:"GO:0038187"(pattern recognition receptor activity)|go:"GO:0042742"(defense response to bacterium)|go:"GO:0042834"(peptidoglycan binding)|go:"GO:0043123"(positive regulation of I-kappaB kinase/NF-kappaB signaling)|go:"GO:0007584"(response to nutrient)|go:"GO:0043330"(response to exogenous dsRNA)|go:"GO:0043406"(positive regulation of MAP kinase activity)|go:"GO:0043552"(positive regulation of phosphatidylinositol 3-kinase activity)|go:"GO:0044877"(protein-containing complex binding)|go:"GO:0045087"(innate immune response)|go:"GO:0045089"(positive regulation of innate immune response)|go:"GO:0045335"(phagocytic vesicle)|go:"GO:0045747"(positive regulation of Notch signaling pathway)|go:"GO:0045944"(positive regulation of transcription by RNA polymerase II)|go:"GO:0046330"(positive regulation of JNK cascade)|go:"GO:0046645"(positive regulation of gamma-delta T cell activation)|go:"GO:0009595"(detection of biotic stimulus)|go:"GO:0046658"(anchored component of plasma membrane)|go:"GO:0009986"(cell surface)|go:"GO:0050679"(positive regulation of epithelial cell proliferation)|go:"GO:0050700"(CARD domain binding)|go:"GO:0050727"(regulation of inflammatory response)|go:"GO:0050731"(positive regulation of peptidyl-tyrosine phosphorylation)|go:"GO:0050766"(positive regulation of phagocytosis)|go:"GO:0050830"(defense response to Gram-positive bacterium)|go:"GO:0050871"(positive regulation of B cell activation)|go:"GO:0051092"(positive regulation of NF-kappaB transcription factor activity)|go:"GO:0051353"(positive regulation of oxidoreductase activity)|go:"GO:0051770"(positive regulation of nitric-oxide synthase biosynthetic process)|go:"GO:0051879"(Hsp90 protein binding)|go:"GO:0060585"(positive regulation of prostaglandin-endoperoxide synthase activity)|go:"GO:0070374"(positive regulation of ERK1 and ERK2 cascade)|go:"GO:0070431"(nucleotide-binding oligomerization domain containing 2 signaling pathway)|go:"GO:0071222"(cellular response to lipopolysaccharide)|go:"GO:0071224"(cellular response to peptidoglycan)|go:"GO:0071225"(cellular response to muramyl dipeptide)|go:"GO:0071407"(cellular response to organic cyclic compound)|go:"GO:0071639"(positive regulation of monocyte chemotactic protein-1 production)|go:"GO:0090022"(regulation of neutrophil chemotaxis)|go:"GO:1900017"(positive regulation of cytokine production involved in inflammatory response)|go:"GO:1901224"(positive regulation of NIK/NF-kappaB signaling)|go:"GO:1902523"(positive regulation of protein K63-linked ubiquitination)|go:"GO:1904417"(positive regulation of xenophagy)|go:"GO:2000110"(negative regulation of macrophage apoptotic process)|go:"GO:2000363"(positive regulation of prostaglandin-E synthase activity)|interpro:IPR001315(Caspase Recruitment)|interpro:IPR001611(Leucine-rich repeat)|interpro:IPR007111(NACHT nucleoside triphosphatase)|interpro:IPR011029(DEATH-like)|interpro:IPR027417|interpro:IPR032675|interpro:IPR041075|interpro:IPR041267|mint:Q9HC29|reactome:R-HSA-168638|reactome:R-HSA-445989|reactome:R-HSA-450302|reactome:R-HSA-450321|reactome:R-HSA-5689896|reactome:R-HSA-9020702|refseq:NP_001280486.1|dip:DIP-41998N refseq:NP_001032836.1|ensembl:ENSMUSG00000026928(gene)|ensembl:ENSMUST00000028294(transcript)|ensembl:ENSMUST00000100303(transcript)|go:"GO:0001819"(positive regulation of cytokine production)|go:"GO:0002446"(neutrophil mediated immunity)|go:"GO:0005737"(cytoplasm)|go:"GO:0005829"(cytosol)|go:"GO:0007249"(I-kappaB kinase/NF-kappaB signaling)|go:"GO:0009620"(response to fungus)|go:"GO:0016064"(immunoglobulin mediated immune response)|go:"GO:0019904"(protein domain specific binding)|go:"GO:0032449"(CBM complex)|go:"GO:0032494"(response to peptidoglycan)|go:"GO:0032495"(response to muramyl dipeptide)|go:"GO:0032663"(regulation of interleukin-2 production)|go:"GO:0032675"(regulation of interleukin-6 production)|go:"GO:0032680"(regulation of tumor necrosis factor production)|go:"GO:0032722"(positive regulation of chemokine production)|go:"GO:0032725"(positive regulation of granulocyte macrophage colony-stimulating factor production)|go:"GO:0032740"(positive regulation of interleukin-17 production)|go:"GO:0032755"(positive regulation of interleukin-6 production)|go:"GO:0032760"(positive regulation of tumor necrosis factor production)|go:"GO:0032874"(positive regulation of stress-activated MAPK cascade)|go:"GO:0032991"(protein-containing complex)|go:"GO:0042493"|go:"GO:0042802"(identical protein binding)|go:"GO:0042803"(protein homodimerization activity)|go:"GO:0042981"(regulation of apoptotic process)|go:"GO:0043123"(positive regulation of I-kappaB kinase/NF-kappaB signaling)|go:"GO:0043280"(positive regulation of cysteine-type endopeptidase activity involved in apoptotic process)|go:"GO:0043330"(response to exogenous dsRNA)|go:"GO:0043621"(protein self-association)|go:"GO:0045089"(positive regulation of innate immune response)|go:"GO:0046330"(positive regulation of JNK cascade)|go:"GO:0046872"(metal ion binding)|go:"GO:0048874"(host-mediated regulation of intestinal microbiota composition)|go:"GO:0050700"(CARD domain binding)|go:"GO:0050830"(defense response to Gram-positive bacterium)|go:"GO:0051092"(positive regulation of NF-kappaB transcription factor activity)|go:"GO:0051260"(protein homooligomerization)|go:"GO:0051607"(defense response to virus)|go:"GO:0061760"(antifungal innate immune response)|go:"GO:0070374"(positive regulation of ERK1 and ERK2 cascade)|go:"GO:1900017"(positive regulation of cytokine production involved in inflammatory response)|go:"GO:2000318"(positive regulation of T-helper 17 type immune response)|interpro:IPR001315(Caspase Recruitment)|interpro:IPR011029(DEATH-like)|interpro:IPR042142|reactome:R-MMU-5607764 - comment:mint|comment:homomint|function:"Induces NF-kappa-B via RICK (CARDIAK, RIP2) and IKK-gamma. Confers responsiveness to intracellular bacterial lipopolysaccharides (LPS)"|function:"Defects in NOD2 are the cause of Blau syndrome (BS) [MIM:186580]. BS is a rare autosomal dominant disorder characterized by early-onset granulomatous arthritis, uveitis and skin rash"|function:"Defects in NOD2 are a cause of susceptibility to Crohn disease (CD) [MIM:266600]. CD is a form of remitting inflammatory bowel disease (IBD). CD may involve any part of the gastrointestinal tract, but most frequently the terminal ileum and colon. Bowel inflammation is transmural and discontinuous. Crohn disease is commonly classified as autoimmune disease"|function:"Defects in NOD2 are a cause of susceptibility to ulcerative colitis [MIM:191390]. It is a chronic inflammatory bowel disease. In ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers. Ulcerative colitis is commonly classified as autoimmune disease"|function:"Defects in NOD2 are the cause of early-onset sarcoidosis (EOS) [MIM:609464]. Sarcoidosis is a multiorganic inflammatory disease with unknown etiology, characterized by the histologic features of non-caseating epithelioid granulomas. In childhood, 2 distinct types of sarcoidosis have been described. Usually the disease is detected in older children by chest radiography and the clinical manifestations are characterized by a classical triad of lung, lymph node, and eye involvement, similar to those in adults. In contrast, early-onset sarcoidosis (EOS), which usually appears in those younger than 4 years of age, 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, EOS is progressive and in many cases causes severe complications, such as blindness, joint destruction, and visceral involvement" - figure legend:f2 f3|comment:"CARD9 was immunoprecipitated by full-length, CARD-NACHT, and NACHT-LRR NOD2 constructs (Figure 2A). Neither the CARDs nor the LRRs alone interacted with CARD9, suggesting that the NACHT domain of NOD2 has a critical role in mediating interaction with CARD9. To further investigate the importance of the NOD2 NACHT domain we tested the impact of a panel of Crohn’s Disease associated single nucleotide polymorphisms (SNP) [33–36] spanning the NACHT on the interaction with CARD9. This included the widely studied R702W SNP. We also tested the hyperactive Blau Syndrome associated SNP R334W [37]. All of the polymorphisms still interacted with CARD9 indicating that these residues, and potentially the surrounding regions of the NACHT,were not crucial for CARD9 interaction (Figure 2B & 2C)."|comment:"we generated further C-terminal NOD2 truncations (Figure 3A) and tested their interaction with CARD9. All of these truncations, including A274stop which lacks any of the NACHT, retained the ability to interact with CARD9 (Figure 3B). Together with the failure of the CARD only construct (residues 1-227 ; Figure 2A & 3B) to interact with CARD9 this indicated that residues 228-274 contain a critical region for CARD9 interaction."|comment:"In summary the NOD2 CARD-NACHT linker (residues 228-274) and the NACHT domain itself contain regions capable of interaction with CARD9"|full coverage:Only protein-protein interactions|curation depth:imex curation taxid:9606(human-293)|taxid:9606(Homo sapiens transformed primary embryonal kidney cells) - 2014/06/12 2014/10/16 rogid:cEF3hnDQW90TWXNDH/uqW6/wMhI9606 rogid:+rEeFRnEaP2LWzs+HArf3Cmi5YQ10090 intact-crc:A17590E45A14F37A|rigid:afRytYsbWhIteSl9g5lLR/miUC0 false flag tag:?-?|binding-associated region:228-274 v5 tag:?-? - - psi-mi:"MI:0113"(western blot) psi-mi:"MI:0113"(western blot)