IntAct European Bioinformatics Institute IntAct intact http://www.ebi.ac.uk/ http://www.ebi.ac.uk/intact/query/${ac} EBI-[0-9]+|IA:[0-9]+ INTerAction database (IntAct) provides an open source database and toolkit for the storage, presentation and analysis of molecular interactions. http://www.ebi.ac.uk/intact European Bioinformatics Institute; Wellcome Trust Genome Campus; Hinxton, Cambridge; CB10 1SD; United Kingdom http://www.ebi.ac.uk/intact/ http://www.ebi.ac.uk/ ikner-2011-1 TWEAK Induces Apoptosis through a Death-signaling Complex Comprising Receptor-interacting Protein 1 (RIP1), Fas-associated Death Domain (FADD), and Caspase-8. human-hsc3 Homo sapiens hsc3 Human oral squamous carcinoma cell line anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Ikner A., Ashkenazi A. Apoptosis - Interactions involving proteins with a function related to apoptosis aa@gene.com J. Biol. Chem. (0021-9258) 2011 Only protein-protein interactions imex curation ikner-2011-2 TWEAK Induces Apoptosis through a Death-signaling Complex Comprising Receptor-interacting Protein 1 (RIP1), Fas-associated Death Domain (FADD), and Caspase-8. human-hec1a Homo sapiens hec1a human endometrial carcinoma cells anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Ikner A., Ashkenazi A. Apoptosis - Interactions involving proteins with a function related to apoptosis aa@gene.com J. Biol. Chem. (0021-9258) 2011 Only protein-protein interactions imex curation ikner-2011-3 TWEAK Induces Apoptosis through a Death-signaling Complex Comprising Receptor-interacting Protein 1 (RIP1), Fas-associated Death Domain (FADD), and Caspase-8. human-hsc3 Homo sapiens hsc3 Human oral squamous carcinoma cell line anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Ikner A., Ashkenazi A. Apoptosis - Interactions involving proteins with a function related to apoptosis aa@gene.com J. Biol. Chem. (0021-9258) 2011 Only protein-protein interactions imex curation ikner-2011-4 TWEAK Induces Apoptosis through a Death-signaling Complex Comprising Receptor-interacting Protein 1 (RIP1), Fas-associated Death Domain (FADD), and Caspase-8. human-hec1a Homo sapiens hec1a human endometrial carcinoma cells anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Ikner A., Ashkenazi A. Apoptosis - Interactions involving proteins with a function related to apoptosis aa@gene.com J. Biol. Chem. (0021-9258) 2011 Only protein-protein interactions imex curation birc2_human Baculoviral IAP repeat-containing protein 2 Inhibitor of apoptosis protein 2 TNFR2-TRAF-signaling complex protein 2 IAP homolog B RING finger protein 48 BIRC2 API1 MIHB RNF48 RING-type E3 ubiquitin transferase BIRC2 Cellular inhibitor of apoptosis 1 protein protein human Homo sapiens Human MHKTASQRLFPGPSYQNIKSIMEDSTILSDWTNSNKQKMKYDFSCELYRMSTYSTFPAGVPVSERSLARAGFYYTGVNDKVKCFCCGLMLDNWKLGDSPIQKHKQLYPSCSFIQNLVSASLGSTSKNTSPMRNSFAHSLSPTLEHSSLFSGSYSSLSPNPLNSRAVEDISSSRTNPYSYAMSTEEARFLTYHMWPLTFLSPSELARAGFYYIGPGDRVACFACGGKLSNWEPKDDAMSEHRRHFPNCPFLENSLETLRFSISNLSMQTHAARMRTFMYWPSSVPVQPEQLASAGFYYVGRNDDVKCFCCDGGLRCWESGDDPWVEHAKWFPRCEFLIRMKGQEFVDEIQGRYPHLLEQLLSTSDTTGEENADPPIIHFGPGESSSEDAVMMNTPVVKSALEMGFNRDLVKQTVQSKILTTGENYKTVNDIVSALLNAEDEKREEEKEKQAEEMASDDLSLIRKNRMALFQQLTCVLPILDNLLKANVINKQEHDIIKQKTQIPLQARELIDTILVKGNAAANIFKNCLKEIDSTLYKNLFVDKNMKYIPTEDVSGLSLEEQLRRLQEERTCKVCMDKEVSVVFIPCGHLVVCQECAPSLRKCPICRGIIKGTVRTFLS tnr12_human Tumor necrosis factor receptor superfamily member 12A TNFRSF12A FN14 Fibroblast growth factor-inducible immediate-early response protein 14 Tweak-receptor protein protein human Homo sapiens Human MARGSLRRLLRLLVLGLWLALLRSVAGEQAPGTAPCSRGSSWSADLDKCMDCASCRARPHSDFCLGCAAAPPAPFRLLWPILGGALSLTFVLGLLSGFLVWRRCRRREKFTTPIEETGGEGCPAVALIQ traf2_human TNF receptor-associated factor 2 TRAF2 TRAP3 Tumor necrosis factor type 2 receptor-associated protein 3 E3 ubiquitin-protein ligase TRAF2 RING-type E3 ubiquitin transferase TRAF2 protein protein human Homo sapiens Human MAAASVTPPGSLELLQPGFSKTLLGTKLEAKYLCSACRNVLRRPFQAQCGHRYCSFCLASILSSGPQNCAACVHEGIYEEGISILESSSAFPDNAARREVESLPAVCPSDGCTWKGTLKEYESCHEGRCPLMLTECPACKGLVRLGEKERHLEHECPERSLSCRHCRAPCCGADVKAHHEVCPKFPLTCDGCGKKKIPREKFQDHVKTCGKCRVPCRFHAIGCLETVEGEKQQEHEVQWLREHLAMLLSSVLEAKPLLGDQSHAGSELLQRCESLEKKTATFENIVCVLNREVERVAMTAEACSRQHRLDQDKIEALSSKVQQLERSIGLKDLAMADLEQKVLEMEASTYDGVFIWKISDFARKRQEAVAGRIPAIFSPAFYTSRYGYKMCLRIYLNGDGTGRGTHLSLFFVVMKGPNDALLRWPFNQKVTLMLLDQNNREHVIDAFRPDVTSSSFQRPVNDMNIASGCPLFCPVSKMEAKNSYVRDDAIFIKAIVDLTGL fadd_human FAS-associated death domain protein FAS-associating death domain-containing protein Mediator of receptor induced toxicity FADD MORT1 GIG3 Growth-inhibiting gene 3 protein protein protein human Homo sapiens Human MDPFLVLLHSVSSSLSSSELTELKFLCLGRVGKRKLERVQSGLDLFSMLLEQNDLEPGHTELLRELLASLRRHDLLRRVDDFEAGAAAGAAPGEEDLCAAFNVICDNVGKDWRRLARQLKVSDTKIDSIEDRYPRNLTERVRESLRIWKNTEKENATVAHLVGALRSCQMNLVADLVQEVQQARDLQNRSGAMSPMSWNSDASTSEAS ripk1_human Receptor-interacting serine/threonine-protein kinase 1 RIPK1 RIP Cell death protein RIP RIP1 Receptor-interacting protein 1 protein protein human Homo sapiens Human MQPDMSLNVIKMKSSDFLESAELDSGGFGKVSLCFHRTQGLMIMKTVYKGPNCIEHNEALLEEAKMMNRLRHSRVVKLLGVIIEEGKYSLVMEYMEKGNLMHVLKAEMSTPLSVKGRIILEIIEGMCYLHGKGVIHKDLKPENILVDNDFHIKIADLGLASFKMWSKLNNEEHNELREVDGTAKKNGGTLYYMAPEHLNDVNAKPTEKSDVYSFAVVLWAIFANKEPYENAICEQQLIMCIKSGNRPDVDDITEYCPREIISLMKLCWEANPEARPTFPGIEEKFRPFYLSQLEESVEEDVKSLKKEYSNENAVVKRMQSLQLDCVAVPSSRSNSATEQPGSLHSSQGLGMGPVEESWFAPSLEHPQEENEPSLQSKLQDEANYHLYGSRMDRQTKQQPRQNVAYNREEERRRRVSHDPFAQQRPYENFQNTEGKGTAYSSAASHGNAVHQPSGLTSQPQVLYQNNGLYSSHGFGTRPLDPGTAGPRVWYRPIPSHMPSLHNIPVPETNYLGNTPTMPFSSLPPTDESIKYTIYNSTGIQIGAYNYMEIGGTSSSLLDSTNTNFKEEPAAKYQAIFDNTTSLTDKHLDPIRENLGKHWKNCARKLGFTQSQIDEIDHDYERDGLKEKVYQMLQKWVMREGIKGATVGKLAQALHQCSRIDLLSSLIYVSQN casp8_human Caspase-8 CASP8 MCH5 ICE-like apoptotic protease 5 MORT1-associated ced-3 homolog FADD-homologous ICE/ced-3-like protease FADD-like ICE Apoptotic cysteine protease Apoptotic protease Mch-5 CAP4 protein protein human Homo sapiens Human MDFSRNLYDIGEQLDSEDLASLKFLSLDYIPQRKQEPIKDALMLFQRLQEKRMLEESNLSFLKELLFRINRLDLLITYLNTRKEEMERELQTPGRAQISAYRVMLYQISEEVSRSELRSFKFLLQEEISKCKLDDDMNLLDIFIEMEKRVILGEGKLDILKRVCAQINKSLLKIINDYEEFSKERSSSLEGSPDEFSNGEELCGVMTISDSPREQDSESQTLDKVYQMKSKPRGYCLIINNHNFAKAREKVPKLHSIRDRNGTHLDAGALTTTFEELHFEIKPHDDCTVEQIYEILKIYQLMDHSNMDCFICCILSHGDKGIIYGTDGQEAPIYELTSQFTGLKCPSLAGKPKVFFIQACQGDNYQKGIPVETDSEEQPYLEMDLSSPQTRYIPDEADFLLGMATVNNCVSYRNPAEGTWYIQSLCQSLRERCPRGDDILTILTEVNYEVSNKDDKKNMGKQMPQPTFTLRKKLVFPSD tnfrsf12a-birc2 1172272 n/a 1172276 unspecified role unspecified role prey prey n/a 1172277 unspecified role unspecified role bait bait living cell living cell physical association physical association false false false Fig. 2a TWEAK (O43508) is required for the interaction to happen. tnfrsf12a-traf2 1172272 n/a 1172277 unspecified role unspecified role bait bait living cell living cell n/a 1172278 unspecified role unspecified role prey prey physical association physical association false false false Fig 2b TWEAK (O43508) is required for the interaction to happen. traf2-tnfrsf12a-1 1172272 n/a 1172278 unspecified role unspecified role bait bait n/a 1172277 unspecified role unspecified role prey prey living cell living cell physical association physical association false false false Fig. 2c TWEAK (O43508) is required for the interaction to happen. ripk1-casp8 1172272 n/a 1172279 unspecified role unspecified role prey prey n/a 1172280 unspecified role unspecified role bait bait n/a 1172281 unspecified role unspecified role prey prey association association false false false Fig. 3b TWEAK (O43508) is required for the interaction to happen. TNR12 knock-down disrupts the interaction (fig. S5). casp8-fadd-9 1172272 n/a 1172281 unspecified role unspecified role bait bait n/a 1172280 unspecified role unspecified role prey prey n/a 1172279 unspecified role unspecified role prey prey association association false false false Fig. 3e, 5f, 6a and 6c TWEAK (O43508) is required for the interaction to happen. TNR12 knock-down disrupts the interaction (fig. S5). CYLD knock-down disrupts the interaction (fig. 6c). tnfrsf12a-birc2-2 1172273 n/a 1172276 unspecified role unspecified role prey prey n/a FN14 1172277 unspecified role unspecified role bait bait living cell living cell n/a 1172278 unspecified role unspecified role prey prey association association false false false Fig. S3 TWEAK (O43508) is required for the interaction to happen. casp8-ripk1 1172274 n/a 1172280 unspecified role unspecified role prey prey n/a 1172281 unspecified role unspecified role bait bait physical association physical association false false false Figs. 3a, 5a and 7e TWEAK (O43508) is required for the interaction to happen. FADD knock-down decreases the CASP8-RIP1K interaction (fig. 3e). TNFR1 knock-down decreases the CASP8-RIP1K interaction (fig. 5a). TNFR1:Fc antagonist blocks TWEAK-induced CASP8-FADD-RIP1K interaction (fig. 5f). CYLD knock-down disrupts TWEAK-induced CASP8-FADD-RIP1K interaction (Fig. 6c). casp8-ripk1-6 1172275 n/a 1172281 unspecified role unspecified role bait bait n/a 1172280 unspecified role unspecified role prey prey physical association physical association false false false Fig. S4 TWEAK (O43508) is required for the interaction to happen.