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/ heidorn-2010-3 Kinase-Dead BRAF and Oncogenic RAS Cooperate to Drive Tumor Progression through CRAF. human-d04 Human D04 cells d04 D04 melanoma cells anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Heidorn SJ., Milagre C., Whittaker S., Nourry A., Niculescu-Duvas I., Dhomen N., Hussain J., Reis-Filho JS., Springer CJ., Pritchard C., Marais R. Cancer - Interactions investigated in the context of cancer richard.marais@icr.ac.uk Cell (0092-8674) 2010 Only protein-protein interactions 20 imex curation heidorn-2010-8 Kinase-Dead BRAF and Oncogenic RAS Cooperate to Drive Tumor Progression through CRAF. human-d04 Human D04 cells d04 D04 melanoma cells anti tag coip anti tag coimmunoprecipitation anti tag coip western blot western blot Immuno blot Immuno blot Heidorn SJ., Milagre C., Whittaker S., Nourry A., Niculescu-Duvas I., Dhomen N., Hussain J., Reis-Filho JS., Springer CJ., Pritchard C., Marais R. Cancer - Interactions investigated in the context of cancer richard.marais@icr.ac.uk Cell (0092-8674) 2010 Only protein-protein interactions 20 imex curation heidorn-2010-1 Kinase-Dead BRAF and Oncogenic RAS Cooperate to Drive Tumor Progression through CRAF. human-mm415 Human MM415 cells mm415 MM415 human melanoma cell line anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Heidorn SJ., Milagre C., Whittaker S., Nourry A., Niculescu-Duvas I., Dhomen N., Hussain J., Reis-Filho JS., Springer CJ., Pritchard C., Marais R. Cancer - Interactions investigated in the context of cancer richard.marais@icr.ac.uk Cell (0092-8674) 2010 Only protein-protein interactions 20 imex curation heidorn-2010-2 Kinase-Dead BRAF and Oncogenic RAS Cooperate to Drive Tumor Progression through CRAF. human-mm485 Human MM485 cells mm485 MM485 human melanoma cell line anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Heidorn SJ., Milagre C., Whittaker S., Nourry A., Niculescu-Duvas I., Dhomen N., Hussain J., Reis-Filho JS., Springer CJ., Pritchard C., Marais R. Cancer - Interactions investigated in the context of cancer richard.marais@icr.ac.uk Cell (0092-8674) 2010 Only protein-protein interactions 20 imex curation heidorn-2010-4 Kinase-Dead BRAF and Oncogenic RAS Cooperate to Drive Tumor Progression through CRAF. human-wm852 Human WM852 cells wm852 WM852 human melonoma cell line anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Heidorn SJ., Milagre C., Whittaker S., Nourry A., Niculescu-Duvas I., Dhomen N., Hussain J., Reis-Filho JS., Springer CJ., Pritchard C., Marais R. Cancer - Interactions investigated in the context of cancer richard.marais@icr.ac.uk Cell (0092-8674) 2010 Only protein-protein interactions 20 imex curation heidorn-2010-5 Kinase-Dead BRAF and Oncogenic RAS Cooperate to Drive Tumor Progression through CRAF. human-sw620 Human caucasian colon adenocarcinoma SW620 cells sw620 Human caucasian colon adenocarcinoma SW620 cells anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Heidorn SJ., Milagre C., Whittaker S., Nourry A., Niculescu-Duvas I., Dhomen N., Hussain J., Reis-Filho JS., Springer CJ., Pritchard C., Marais R. Cancer - Interactions investigated in the context of cancer richard.marais@icr.ac.uk Cell (0092-8674) 2010 Only protein-protein interactions 20 imex curation heidorn-2010-6 Kinase-Dead BRAF and Oncogenic RAS Cooperate to Drive Tumor Progression through CRAF. human-hct116 Human colon carcinoma HCT116 cells hct116 Human colon carcinoma line HCT116 anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Heidorn SJ., Milagre C., Whittaker S., Nourry A., Niculescu-Duvas I., Dhomen N., Hussain J., Reis-Filho JS., Springer CJ., Pritchard C., Marais R. Cancer - Interactions investigated in the context of cancer richard.marais@icr.ac.uk Cell (0092-8674) 2010 Only protein-protein interactions 20 imex curation heidorn-2010-7 Kinase-Dead BRAF and Oncogenic RAS Cooperate to Drive Tumor Progression through CRAF. human-wm1791c Homo sapiens wm1791c Human WM1791c melanoma cells anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Heidorn SJ., Milagre C., Whittaker S., Nourry A., Niculescu-Duvas I., Dhomen N., Hussain J., Reis-Filho JS., Springer CJ., Pritchard C., Marais R. Cancer - Interactions investigated in the context of cancer richard.marais@icr.ac.uk Cell (0092-8674) 2010 Only protein-protein interactions 20 imex curation heidorn-2010-9 Kinase-Dead BRAF and Oncogenic RAS Cooperate to Drive Tumor Progression through CRAF. human-pmwk Human PMWK melanoma cells pmwk Human PMWK melanoma cells anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Heidorn SJ., Milagre C., Whittaker S., Nourry A., Niculescu-Duvas I., Dhomen N., Hussain J., Reis-Filho JS., Springer CJ., Pritchard C., Marais R. Cancer - Interactions investigated in the context of cancer richard.marais@icr.ac.uk Cell (0092-8674) 2010 Only protein-protein interactions 20 imex curation heidorn-2010-10 Kinase-Dead BRAF and Oncogenic RAS Cooperate to Drive Tumor Progression through CRAF. mouse-melanoma Mouse melanoma melanoma Melanoma anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Heidorn SJ., Milagre C., Whittaker S., Nourry A., Niculescu-Duvas I., Dhomen N., Hussain J., Reis-Filho JS., Springer CJ., Pritchard C., Marais R. Cancer - Interactions investigated in the context of cancer richard.marais@icr.ac.uk Cell (0092-8674) 2010 Only protein-protein interactions 20 imex curation braf_human Serine/threonine-protein kinase B-raf BRAF BRAF1 RAFB1 v-Raf murine sarcoma viral oncogene homolog B1 p94 Proto-oncogene B-Raf protein protein human Homo sapiens Human MAALSGGGGGGAEPGQALFNGDMEPEAGAGAGAAASSAADPAIPEEVWNIKQMIKLTQEHIEALLDKFGGEHNPPSIYLEAYEEYTSKLDALQQREQQLLESLGNGTDFSVSSSASMDTVTSSSSSSLSVLPSSLSVFQNPTDVARSNPKSPQKPIVRVFLPNKQRTVVPARCGVTVRDSLKKALMMRGLIPECCAVYRIQDGEKKPIGWDTDISWLTGEELHVEVLENVPLTTHNFVRKTFFTLAFCDFCRKLLFQGFRCQTCGYKFHQRCSTEVPLMCVNYDQLDLLFVSKFFEHHPIPQEEASLAETALTSGSSPSAPASDSIGPQILTSPSPSKSIPIPQPFRPADEDHRNQFGQRDRSSSAPNVHINTIEPVNIDDLIRDQGFRGDGGSTTGLSATPPASLPGSLTNVKALQKSPGPQRERKSSSSSEDRNRMKTLGRRDSSDDWEIPDGQITVGQRIGSGSFGTVYKGKWHGDVAVKMLNVTAPTPQQLQAFKNEVGVLRKTRHVNILLFMGYSTKPQLAIVTQWCEGSSLYHHLHIIETKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLATVKSRWSGSHQFEQLSGSILWMAPEVIRMQDKNPYSFQSDVYAFGIVLYELMTGQLPYSNINNRDQIIFMVGRGYLSPDLSKVRSNCPKAMKRLMAECLKKKRDERPLFPQILASIELLARSLPKIHRSASEPSLNRAGFQTEDFSLYACASPKTPIQAGGYGAFPVH raf1_human RAF proto-oncogene serine/threonine-protein kinase RAF1 RAF Proto-oncogene c-RAF Raf-1 protein protein human Homo sapiens Human MEHIQGAWKTISNGFGFKDAVFDGSSCISPTIVQQFGYQRRASDDGKLTDPSKTSNTIRVFLPNKQRTVVNVRNGMSLHDCLMKALKVRGLQPECCAVFRLLHEHKGKKARLDWNTDAASLIGEELQVDFLDHVPLTTHNFARKTFLKLAFCDICQKFLLNGFRCQTCGYKFHEHCSTKVPTMCVDWSNIRQLLLFPNSTIGDSGVPALPSLTMRRMRESVSRMPVSSQHRYSTPHAFTFNTSSPSSEGSLSQRQRSTSTPNVHMVSTTLPVDSRMIEDAIRSHSESASPSALSSSPNNLSPTGWSQPKTPVPAQRERAPVSGTQEKNKIRPRGQRDSSYYWEIEASEVMLSTRIGSGSFGTVYKGKWHGDVAVKILKVVDPTPEQFQAFRNEVAVLRKTRHVNILLFMGYMTKDNLAIVTQWCEGSSLYKHLHVQETKFQMFQLIDIARQTAQGMDYLHAKNIIHRDMKSNNIFLHEGLTVKIGDFGLATVKSRWSGSQQVEQPTGSVLWMAPEVIRMQDNNPFSFQSDVYSYGIVLYELMTGELPYSHINNRDQIIFMVGRGYASPDLSKLYKNCPKAMKRLVADCVKKVKEERPLFPQILSSIELLQHSLPKINRSASEPSLHRAAHTEDINACTLTTSPRLPVF raf1_mouse RAF proto-oncogene serine/threonine-protein kinase Raf1 Craf Proto-oncogene c-RAF Raf-1 protein protein mouse Mus musculus Mouse MEHIQGAWKTISNGFGLKDAVFDGSSCISPTIVQQFGYQRRASDDGKLTDSSKTSNTIRVFLPNKQRTVVNVRNGMSLHDCLMKALKVRGLQPECCAVFRLLQEHKGKKARLDWNTDAASLIGEELQVDFLDHVPLTTHNFARKTFLKLAFCDICQKFLLNGFRCQTCGYKFHEHCSTKVPTMCVDWSNIRQLLLFPNSTVGDSGVPAPPSFPMRRMRESVSRMPASSQHRYSTPHAFTFNTSSPSSEGSLSQRQRSTSTPNVHMVSTTLHVDSRMIEDAIRSHSESASPSALSSSPNNLSPTGWSQPKTPVPAQRERAPGSGTQEKNKIRPRGQRDSSYYWEIEASEVMLSTRIGSGSFGTVYKGKWHGDVAVKILKVVDPTPEQLQAFRNEVAVLRKTRHVNILLFMGYMTKDNLAIVTQWCEGSSLYKHLHVQETKFQMFQLIDIARQTAQGMDYLHAKNIIHRDMKSNNIFLHEGLTVKIGDFGLATVKSRWSGSQQVEQPTGSVLWMAPEVIRMQDDNPFSFQSDVYSYGIVLYELMAGELPYAHINNRDQIIFMVGRGYASPDLSRLYKNCPKAMKRLVADCVKKVKEERPLFPQILSSIELLQHSLPKINRSASEPSLHRAAHTEDINACTLTTSPRLPVF braf_mouse Serine/threonine-protein kinase B-raf Braf B-raf Proto-oncogene B-Raf protein protein mouse Mus musculus Mouse MAALSGGGGSSSGGGGGGGGGGGGGDGGGGAEQGQALFNGDMEPEAGAGAAASSAADPAIPEEVWNIKQMIKLTQEHIEALLDKFGGEHNPPSIYLEAYEEYTSKLDALQQREQQLLESLVFQTPTDASRNNPKSPQKPIVRVFLPNKQRTVVPARCGVTVRDSLKKALMMRGLIPECCAVYRIQDGEKKPIGWDTDISWLTGEELHVEVLENVPLTTHNFVRKTFFTLAFCDFCRKLLFQGFRCQTCGYKFHQRCSTEVPLMCVNYDQLDLLFVSKFFEHHPVPQEEASFPETALPSGSSSAPPSDSTGPQILTSPSPSKSIPIPQPFRPADEDHRNQFGQRDRSSSAPNVHINTIEPVNIDDLIRDQGFRGDGGSTTGLSATPPASLPGSLTNVKALQKSPGPQRERKSSSSSSSEDRSRMKTLGRRDSSDDWEIPDGQITVGQRIGSGSFGTVYKGKWHGDVAVKMLNVTAPTPQQLQAFKNEVGVLRKTRHVNILLFMGYSTKPQLAIVTQWCEGSSLYHHLHIIETKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLATVKSRWSGSHQFEQLSGSILWMAPEVIRMQDKNPYSFQSDVYAFGIVLYELMTGQLPYSNINNRDQIIFMVGRGYLSPDLSKVRSNCPKAMKRLMAECLKKKRDERPLFPQILASIELLARSLPKIHRSASEPSLNRAGFQTEDFSLYACASPKTPIQAGGYGGFPVH braf-raf1-3 Interaction between BRAF and RAF1 (CRAF) demonstrated by coimmunoprecipitation 882382 n/a 882392 unspecified role unspecified role bait bait n/a 882393 unspecified role unspecified role prey prey physical association physical association false false false Sorafenib (class II (inactive conformation binder) Raf inhibitor) 885-A selective BRAF inhibitor Fig. 2A braf-raf1-7 Interaction between BRAF and RAF1 (CRAF) demonstrated by coimmunoprecipitation 882382 n/a 882392 unspecified role unspecified role prey prey n/a 882393 unspecified role unspecified role bait bait physical association physical association false false false Sorafenib (class II (inactive conformation binder) Raf inhibitor) 885-A selective BRAf inhibitor Fig. 2A, 2B, 3F, Supp Fig. 4B The MEK inhibitor PD184352 stabilizes BRAF binding to CRAF in the presence of the BRAF inhibitor PLX4720 BRAF bound to CRAF is hyperphosphorylated through MEK-ERK-dependent and MEK-ERK-independent mechanisms, but it appears that this phosphorylation is not required for BRAF binding to CRAF. Pan-RAF inhibitor ZM336372 an-RAF inhibitor RAF265 braf-raf1-18 Interaction between BRAF and RAF1 (CRAF) demonstrated by coimmunoprecipitation 882382 n/a 882393 unspecified role unspecified role bait bait n/a 882392 unspecified role unspecified role prey prey n-terminal myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false P15056:p.Thr529Asn mutation decreasing mutation decreasing interaction hotspot hotspot mutation decreasing mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain false physical association physical association false false false 885-A selective BRAf inhibitor Fig. 4C Thr529Asn mutation of BRAf appears to make the protein insensitive to 885-A treatment. braf-raf1-15 Interaction between BRAF and RAF1 (CRAF) demonstrated by coimmunoprecipitation 882383 n/a 882393 unspecified role unspecified role bait bait n-terminal myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false P04049:p.Arg89Leu mutation decreasing mutation decreasing interaction hotspot hotspot mutation decreasing certain certain sequence position certain certain certain sequence position certain false n/a 882392 unspecified role unspecified role prey prey physical association physical association false false false 885-A selective BRAF inhibitor Fig. 3A braf-raf1-16 Interaction between BRAF and RAF1 (CRAF) demonstrated by coimmunoprecipitation 882383 n/a 882392 unspecified role unspecified role bait bait n-terminal myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false P15056:p.Arg188Leu mutation decreasing mutation decreasing interaction hotspot hotspot mutation decreasing mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain false n/a 882393 unspecified role unspecified role prey prey physical association physical association false false false 885-A selective BRAF inhibitor Fig. 3B, 4D braf-raf1-19 Interaction between BRAF and RAF1 (CRAF) demonstrated by coimmunoprecipitation 882383 n/a 882392 unspecified role unspecified role prey prey n/a 882393 unspecified role unspecified role bait bait n-terminal 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 P04049:p.Arg89Leu mutation decreasing mutation decreasing interaction hotspot hotspot mutation decreasing certain certain sequence position certain certain certain sequence position certain false physical association physical association false false false 885-A selective BRAF inhibitor Fig. 4H Sorafenib, a selective BRAF inhibitor braf-raf1-1 Interaction between BRAF and RAF1 (CRAF) demonstrated by coimmunoprecipitation 882384 n/a 882393 unspecified role unspecified role prey prey n/a 882392 unspecified role unspecified role bait bait physical association physical association false false false Sorafenib (class II (inactive conformation binder) Raf inhibitor) 885-A selective BRAf inhibitor Fig. 2A braf-raf1-5 Interaction between BRAF and RAF1 (CRAF) demonstrated by coimmunoprecipitation 882384 n/a 882392 unspecified role unspecified role prey prey n/a 882393 unspecified role unspecified role bait bait physical association physical association false false false Sorafenib (class II (inactive conformation binder) Raf inhibitor) 885-A selective BRAf inhibitor Fig. 2A braf-raf1-2 Interaction between BRAF and RAF1 (CRAF) demonstrated by coimmunoprecipitation 882385 n/a 882393 unspecified role unspecified role prey prey n/a 882392 unspecified role unspecified role bait bait physical association physical association false false false Sorafenib (class II (inactive conformation binder) Raf inhibitor) 885-A selective BRAf inhibitor Fig. 2A braf-raf1-6 Interaction between BRAF and RAF1 (CRAF) demonstrated by coimmunoprecipitation 882385 n/a 882392 unspecified role unspecified role prey prey n/a 882393 unspecified role unspecified role bait bait physical association physical association false false false Sorafenib (class II (inactive conformation binder) Raf inhibitor) 885-A selective BRAf inhibitor Fig. 2A braf-raf1-4 Interaction between BRAF and RAF1 (CRAF) demonstrated by coimmunoprecipitation 882386 n/a 882392 unspecified role unspecified role bait bait n/a 882393 unspecified role unspecified role prey prey physical association physical association false false false Sorafenib (class II (inactive conformation binder) Raf inhibitor) 885-A selective BRAF inhibitor Fig. 2A braf-raf1-8 Interaction between BRAF and RAF1 (CRAF) demonstrated by coimmunoprecipitation 882386 n/a 882393 unspecified role unspecified role bait bait n/a 882392 unspecified role unspecified role prey prey physical association physical association false false false Sorafenib (class II (inactive conformation binder) Raf inhibitor) 885-A selective BRAf inhibitor Fig. 2A braf-raf1-9 Interaction between BRAF and RAF1 (CRAF) demonstrated by coimmunoprecipitation 882387 n/a 882393 unspecified role unspecified role prey prey n/a 882392 unspecified role unspecified role bait bait physical association physical association false false false Sorafenib (class II (inactive conformation binder) Raf inhibitor) 885-A selective BRAF inhibitor Fig. 2C braf-raf1-10 Interaction between BRAF and RAF1 (CRAF) demonstrated by coimmunoprecipitation 882387 n/a 882392 unspecified role unspecified role prey prey n/a 882393 unspecified role unspecified role bait bait physical association physical association false false false Sorafenib (class II (inactive conformation binder) Raf inhibitor) 885-A selective BRAF inhibitor Fig. 2C braf-raf1-11 Interaction between BRAF and RAF1 (CRAF) demonstrated by coimmunoprecipitation 882388 n/a 882393 unspecified role unspecified role prey prey n/a 882392 unspecified role unspecified role bait bait physical association physical association false false false Sorafenib (class II (inactive conformation binder) Raf inhibitor) 885-A selective BRAF inhibitor Fig. 2C braf-raf1-12 Interaction between BRAF and RAF1 (CRAF) demonstrated by coimmunoprecipitation 882388 n/a 882392 unspecified role unspecified role prey prey n/a 882393 unspecified role unspecified role bait bait physical association physical association false false false Sorafenib (class II (inactive conformation binder) Raf inhibitor) 885-A selective BRAF inhibitor Fig. 2C braf-raf1-13 Interaction between BRAF and RAF1 (CRAF) demonstrated by coimmunoprecipitation 882389 n/a 882393 unspecified role unspecified role prey prey n/a 882392 unspecified role unspecified role bait bait physical association physical association false false false Sorafenib (class II (inactive conformation binder) Raf inhibitor) 885-A selective BRAF inhibitor Fig. 2C braf-raf1-14 Interaction between BRAF and RAF1 (CRAF) demonstrated by coimmunoprecipitation 882389 n/a 882392 unspecified role unspecified role prey prey n/a 882393 unspecified role unspecified role bait bait physical association physical association false false false Sorafenib (class II (inactive conformation binder) Raf inhibitor) 885-A selective BRAF inhibitor Fig. 2C braf-raf1-17 Interaction between BRAF and RAF1 (CRAF) demonstrated by coimmunoprecipitation 882390 n/a 882393 unspecified role unspecified role bait bait n/a 882392 unspecified role unspecified role prey prey physical association physical association false false false 885-A selective BRAF inhibitor Fig. 3D braf-raf1-20 Interaction between BRAF and RAF1 (CRAF) demonstrated by coimmunoprecipitation 882391 n/a 882394 unspecified role unspecified role bait bait n/a 882395 unspecified role unspecified role prey prey P28028:p.Asp579Ala mutation mutation certain certain sequence position certain certain certain sequence position certain false physical association physical association false false false Fig. 6E