MINT MINT, Dpt of Biology, University of Rome Tor Vergata MINT http://mint.bio.uniroma2.it/mint url>http://mint.bio.uniroma2.it/mint/ https://mint.bio.uniroma2.it MINT-[0-9]+ https://mint.bio.uniroma2.it/index.php/results-interactions/?id=${ac} The Molecular INTeraction database (MINT) is a relational database designed to store interactions between biological molecules. http://mint.bio.uniroma2.it http://mint.bio.uniroma2.it/mint anonymous-2014z-1 Interaction between NOD2 and CARD9 involves the NOD2 NACHT and the linker region between the NOD2 CARDs and NACHT domain human-293 Homo sapiens transformed primary embryonal kidney cells Human 293 Transformed human primary embryonal kidney cells. The Cell type named 293 is synonymous with HEK-293. anti tag coip anti tag coimmunoprecipitation anti tag coip western blot western blot Immuno blot Immuno blot tpm22@cam.ac.uk 2014 imex curation Parkhouse R., Boyle J.P., Mayle S., Sawmynaden K., Rittinger K., Monie T.P. FEBS Lett. (0014-5793) Only protein-protein interactions nod2_human Nucleotide-binding oligomerization domain-containing protein 2 IBD1 NOD2 CARD15 Caspase recruitment domain-containing protein 15 Inflammatory bowel disease protein 1 protein protein human Homo sapiens Human MGEEGGSASHDEEERASVLLGHSPGCEMCSQEAFQAQRSQLVELLVSGSLEGFESVLDWLLSWEVLSWEDYEGFHLLGQPLSHLARRLLDTVWNKGTWACQKLIAAAQEAQADSQSPKLHGCWDPHSLHPARDLQSHRPAIVRRLHSHVENMLDLAWERGFVSQYECDEIRLPIFTPSQRARRLLDLATVKANGLAAFLLQHVQELPVPLALPLEAATCKKYMAKLRTTVSAQSRFLSTYDGAETLCLEDIYTENVLEVWADVGMAGPPQKSPATLGLEELFSTPGHLNDDADTVLVVGEAGSGKSTLLQRLHLLWAAGQDFQEFLFVFPFSCRQLQCMAKPLSVRTLLFEHCCWPDVGQEDIFQLLLDHPDRVLLTFDGFDEFKFRFTDRERHCSPTDPTSVQTLLFNLLQGNLLKNARKVVTSRPAAVSAFLRKYIRTEFNLKGFSEQGIELYLRKRHHEPGVADRLIRLLQETSALHGLCHLPVFSWMVSKCHQELLLQEGGSPKTTTDMYLLILQHFLLHATPPDSASQGLGPSLLRGRLPTLLHLGRLALWGLGMCCYVFSAQQLQAAQVSPDDISLGFLVRAKGVVPGSTAPLEFLHITFQCFFAAFYLALSADVPPALLRHLFNCGRPGNSPMARLLPTMCIQASEGKDSSVAALLQKAEPHNLQITAAFLAGLLSREHWGLLAECQTSEKALLRRQACARWCLARSLRKHFHSIPPAAPGEAKSVHAMPGFIWLIRSLYEMQEERLARKAARGLNVGHLKLTFCSVGPTECAALAFVLQHLRRPVALQLDYNSVGDIGVEQLLPCLGVCKALYLRDNNISDRGICKLIECALHCEQLQKLALFNNKLTDGCAHSMAKLLACRQNFLALRLGNNYITAAGAQVLAEGLRGNTSLQFLGFWGNRVGDEGAQALAEALGDHQSLRWLSLVGNNIGSVGAQALALMLAKNVMLEELCLEENHLQDEGVCSLAEGLKKNSSLKILKLSNNCITYLGAEALLQALERNDTILEVWLRGNTFSLEEVDKLGCRDTRLLL mint homomint Induces NF-kappa-B via RICK (CARDIAK, RIP2) and IKK-gamma. Confers responsiveness to intracellular bacterial lipopolysaccharides (LPS) 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 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 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 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 card9_mouse Caspase recruitment domain-containing protein 9 Card9 protein protein mouse Mus musculus Mouse MSDYENDDECWSTLESFRVKLISVIDPSRITPYLRQCKVLNPDDEEQVLSDPNLVIRKRKVGVLLDILQRTGHKGYVAFLESLELYYPQLYRKVTGKEPARVFSMIIDASGESGLTQLLMTEVMKLQKKVQDLTALLSSKDDFIKELRVKDSLLRKHQERVQRLKEECELSSAELKRCKDENYELAMCLAHLSEEKGAALMRNRDLQLEVDRLRHSLMKAEDDCKVERKHTLKLRHAMEQRPSQELLWELQQEKDLLQARVQELQVSVQEGKLDRNSPYIQVLEEDWRQALQEHQKQVSTIFSLRKDLRQAETLRARCTEEKEMFELQCLALRKDAKMYKDRIEAILLQMEEVSIERDQAMASREELHAQCTQSFQDKDKLRKLVRELGEKADELQLQLFQTESRLLAAEGRLKQQQLDMLILSSDLEDSSPRNSQELSLPQDLEEDAQLSDKGVLADRESPEQPFMALNKEHLSLTHGMGPSSSEPPEKERRRLKESFENYRRKRALRKMQNSWRQGEGDRGNTTGSDNTDTEGS card9-nod2 1546953 n/a NOD2 1546954 western blot western blot Immuno blot Immuno blot unspecified role unspecified role bait bait over-expressed over expressed level over-expressed living cell living cell tag flag tag flag tag FLAG-tagged FLAG DYKDDDDKV epitope tag DYKDDDDKV epitope tag FLAG FLAG-tagged undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false range binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain false n/a CARD9 1546955 western blot western blot Immuno blot Immuno blot unspecified role unspecified role prey prey over-expressed over expressed level over-expressed living cell living cell tag v5 tag v5 tag GKPIPNPLLGLDST epitope tag GKPIPNPLLGLDST epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false physical association physical association false false false f2 f3 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). 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. In summary the NOD2 CARD-NACHT linker (residues 228-274) and the NACHT domain itself contain regions capable of interaction with CARD9