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/ poussin-2013-1 human-hep_3b Homo sapiens hepatocellular carcinoma (HCC) cells (p53-null). hep_3b human hepatocellular carcinoma (HCC) cells (p53-null). anti tag coip anti tag coimmunoprecipitation anti tag coip anti tag western anti tag western blot anti tag western Poussin K., Pilati C., Couchy G., Calderaro J., Bioulac-Sage P., Bacq Y., Paradis V., Leteurtre E., Sturm N., Ramos J., Guettier C., Bardier-Dupas A., Boulai A., Wendum D., Selves J., Izard T., Nault JC., Zucman-Rossi J. jessica.zucman-rossi@inserm.fr Oncoimmunology 2013 imex curation Only protein-protein interactions imex curation poussin-2013-2 human-hep_3b Homo sapiens hepatocellular carcinoma (HCC) cells (p53-null). hep_3b human hepatocellular carcinoma (HCC) cells (p53-null). anti bait coip anti bait coimmunoprecipitation anti bait coip anti tag western anti tag western blot anti tag western Poussin K., Pilati C., Couchy G., Calderaro J., Bioulac-Sage P., Bacq Y., Paradis V., Leteurtre E., Sturm N., Ramos J., Guettier C., Bardier-Dupas A., Boulai A., Wendum D., Selves J., Izard T., Nault JC., Zucman-Rossi J. jessica.zucman-rossi@inserm.fr Oncoimmunology 2013 imex curation Only protein-protein interactions imex curation il6rb_human Interleukin-6 receptor subunit beta IL6ST Interleukin-6 signal transducer Membrane glycoprotein 130 CDw130 Oncostatin-M receptor subunit alpha protein protein human Homo sapiens Human MLTLQTWLVQALFIFLTTESTGELLDPCGYISPESPVVQLHSNFTAVCVLKEKCMDYFHVNANYIVWKTNHFTIPKEQYTIINRTASSVTFTDIASLNIQLTCNILTFGQLEQNVYGITIISGLPPEKPKNLSCIVNEGKKMRCEWDGGRETHLETNFTLKSEWATHKFADCKAKRDTPTSCTVDYSTVYFVNIEVWVEAENALGKVTSDHINFDPVYKVKPNPPHNLSVINSEELSSILKLTWTNPSIKSVIILKYNIQYRTKDASTWSQIPPEDTASTRSSFTVQDLKPFTEYVFRIRCMKEDGKGYWSDWSEEASGITYEDRPSKAPSFWYKIDPSHTQGYRTVQLVWKTLPPFEANGKILDYEVTLTRWKSHLQNYTVNATKLTVNLTNDRYLATLTVRNLVGKSDAAVLTIPACDFQATHPVMDLKAFPKDNMLWVEWTTPRESVKKYILEWCVLSDKAPCITDWQQEDGTVHRTYLRGNLAESKCYLITVTPVYADGPGSPESIKAYLKQAPPSKGPTVRTKKVGKNEAVLEWDQLPVDVQNGFIRNYTIFYRTIIGNETAVNVDSSHTEYTLSSLTSDTLYMVRMAAYTDEGGKDGPEFTFTTPKFAQGEIEAIVVPVCLAFLLTTLLGVLFCFNKRDLIKKHIWPNVPDPSKSHIAQWSPHTPPRHNFNSKDQMYSDGNFTDVSVVEIEANDKKPFPEDLKSLDLFKKEKINTEGHSSGIGGSSCMSSSRPSISSSDENESSQNTSSTVQYSTVVHSGYRHQVPSVQVFSRSESTQPLLDSEERPEDLQLVDHVDGGDGILPRQQYFKQNCSQHESSPDISHFERSKQVSSVNEEDFVRLKQQISDHISQSCGSGQMKMFQEVSAADAFGPGTEGQVERFETVGMEAATDEGMPKSYLPQTVRQGGYMPQ osmr_human Oncostatin-M-specific receptor subunit beta OSMRB Interleukin-31 receptor subunit beta OSMR protein protein human Homo sapiens Human MALFAVFQTTFFLTLLSLRTYQSEVLAERLPLTPVSLKVSTNSTRQSLHLQWTVHNLPYHQELKMVFQIQISRIETSNVIWVGNYSTTVKWNQVLHWSWESELPLECATHFVRIKSLVDDAKFPEPNFWSNWSSWEEVSVQDSTGQDILFVFPKDKLVEEGTNVTICYVSRNIQNNVSCYLEGKQIHGEQLDPHVTAFNLNSVPFIRNKGTNIYCEASQGNVSEGMKGIVLFVSKVLEEPKDFSCETEDFKTLHCTWDPGTDTALGWSKQPSQSYTLFESFSGEKKLCTHKNWCNWQITQDSQETYNFTLIAENYLRKRSVNILFNLTHRVYLMNPFSVNFENVNATNAIMTWKVHSIRNNFTYLCQIELHGEGKMMQYNVSIKVNGEYFLSELEPATEYMARVRCADASHFWKWSEWSGQNFTTLEAAPSEAPDVWRIVSLEPGNHTVTLFWKPLSKLHANGKILFYNVVVENLDKPSSSELHSIPAPANSTKLILDRCSYQICVIANNSVGASPASVIVISADPENKEVEEERIAGTEGGFSLSWKPQPGDVIGYVVDWCDHTQDVLGDFQWKNVGPNTTSTVISTDAFRPGVRYDFRIYGLSTKRIACLLEKKTGYSQELAPSDNPHVLVDTLTSHSFTLSWKDYSTESQPGFIQGYHVYLKSKARQCHPRFEKAVLSDGSECCKYKIDNPEEKALIVDNLKPESFYEFFITPFTSAGEGPSATFTKVTTPDEHSSMLIHILLPMVFCVLLIMVMCYLKSQWIKETCYPDIPDPYKSSILSLIKFKENPHLIIMNVSDCIPDAIEVVSKPEGTKIQFLGTRKSLTETELTKPNYLYLLPTEKNHSGPGPCICFENLTYNQAASDSGSCGHVPVSPKAPSMLGLMTSPENVLKALEKNYMNSLGEIPAGETSLNYVSQLASPMFGDKDSLPTNPVEAPHCSEYKMQMAVSLRLALPPPTENSSLSSITLLDPGEHYC il6st-il6st-3 3474504 N/A 3474506 unspecified role unspecified role bait bait over-expressed over expressed level over-expressed flag tag flag tag flag tag FLAG-tagged FLAG DYKDDDDKV epitope tag DYKDDDDKV epitope tag FLAG FLAG-tagged c-term range C-terminal range c-term range c-term range C-terminal range c-term range false p.Ala418_Phe421del mutation causing mutation causing an interaction mutation enabling interaction mutation causing mutation causing an interaction certain certain sequence position certain certain certain sequence position certain false N/A 3474506 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed myc tag myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range false p.Ala418_Phe421del mutation causing mutation causing an interaction mutation enabling interaction mutation causing mutation causing an interaction certain certain sequence position certain certain certain sequence position certain false physical association physical association false false false Fig. 3A As previously shown,5 wild-type gp130 do not homodimerize in the absence of IL-6. Conversely, IHCA-associated gp130 mutants are fully capable of homodimerizing as well as of heterodimerizing with wild-type gp130 in the absence of IL-6 (Fig. 3A). il6st-il6st-2 3474504 N/A 3474506 unspecified role unspecified role bait bait over-expressed over expressed level over-expressed flag tag flag tag flag tag FLAG-tagged FLAG DYKDDDDKV epitope tag DYKDDDDKV epitope tag FLAG FLAG-tagged c-term range C-terminal range c-term range c-term range C-terminal range c-term range false p.Tyr186_Tyr190del mutation causing mutation causing an interaction mutation enabling interaction mutation causing mutation causing an interaction certain certain sequence position certain certain certain sequence position certain false N/A 3474506 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed myc tag myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range false p.Tyr186_Tyr190del mutation causing mutation causing an interaction mutation enabling interaction mutation causing mutation causing an interaction certain certain sequence position certain certain certain sequence position certain false physical association physical association false false false Fig. 3A As previously shown,5 wild-type gp130 do not homodimerize in the absence of IL-6. Conversely, IHCA-associated gp130 mutants are fully capable of homodimerizing as well as of heterodimerizing with wild-type gp130 in the absence of IL-6 (Fig. 3A). il6st-il6st-4 3474505 N/A 3474507 unspecified role unspecified role bait bait physiological level physiological level endogenous level endogenous endogenous endogenous level N/A 3474506 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed flag tag flag tag flag tag FLAG-tagged FLAG DYKDDDDKV epitope tag DYKDDDDKV epitope tag FLAG FLAG-tagged c-term range C-terminal range c-term range c-term range C-terminal range c-term range false p.Tyr186_Tyr190del mutation increasing strength mutation increasing interaction strength mutation increasing strength certain certain sequence position certain certain certain sequence position certain false physical association physical association false false false Fig. 3D Gp130 also binds to the OSMR, an interaction that is required for OSMR signaling. As anticipated, the interaction between wild-type gp130 and OSMR in Hep3B cells required OSM, whereas gp130 mutants formed heterodimers with OSMR even in the absence of its ligand (Fig. 3D). osmr-il6st-1 3474505 N/A 3474507 unspecified role unspecified role bait bait physiological level physiological level endogenous level endogenous endogenous endogenous level N/A 3474506 unspecified role unspecified role prey prey over-expressed over expressed level over-expressed p.Tyr186_Tyr190del mutation with no effect mutation with no effect mutation with no effect mutation not affecting interaction certain certain sequence position certain certain certain sequence position certain false flag tag flag tag flag tag FLAG-tagged FLAG DYKDDDDKV epitope tag DYKDDDDKV epitope tag FLAG FLAG-tagged c-term range C-terminal range c-term range c-term range C-terminal range c-term range false physical association physical association false false false Fig. 3D Gp130 also binds to the OSMR, an interaction that is required for OSMR signaling. As anticipated, the interaction between wild-type gp130 and OSMR in Hep3B cells required OSM, whereas gp130 mutants formed heterodimers with OSMR even in the absence of its ligand (Fig. 3D). OSM ligand