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/ CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibitor Persistence and Demonstrates Efficacy in Myeloproliferative Neoplasms. CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibitor Persistence and Demonstrates Efficacy in Myeloproliferative Neoplasms. Cancer cell 2015 imex curation Meyer SC., Keller MD., Chiu S., Koppikar P., Guryanova OA., Rapaport F., Xu K., Manova K., Pankov D., O'Reilly RJ., Kleppe M., McKenney AS., Shih AH., Shank K., Ahn J., Papalexi E., Spitzer B., Socci N., Viale A., Mandon E., Ebel N., Andraos R., Rubert J., Dammassa E., Romanet V., Dölemeyer A., Zender M., Heinlein M., Rampal R., Weinberg RS., Hoffman R., Sellers WR., Hofmann F., Murakami M., Baffert F., Gaul C., Radimerski T., Levine RL. Cancer - Interactions investigated in the context of cancer thomas.radimerski@novartis.com,leviner@mskcc.org 05-Sep-2017: Contacted by IntAct-Help. Only protein-protein interactions imex curation human-set2 SET2 - Human acute leukemia cell line (megakaryoblastic) set2 SET2 Human acute leukemia cell line (megakaryoblastic) anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Meyer SC., Keller MD., Chiu S., Koppikar P., Guryanova OA., Rapaport F., Xu K., Manova K., Pankov D., O'Reilly RJ., Kleppe M., McKenney AS., Shih AH., Shank K., Ahn J., Papalexi E., Spitzer B., Socci N., Viale A., Mandon E., Ebel N., Andraos R., Rubert J., Dammassa E., Romanet V., Dölemeyer A., Zender M., Heinlein M., Rampal R., Weinberg RS., Hoffman R., Sellers WR., Hofmann F., Murakami M., Baffert F., Gaul C., Radimerski T., Levine RL. Cancer - Interactions investigated in the context of cancer Supp Fig 1 results entered separately as no idea what antibodies were used to detect phosph-ed molecules. Cells were grown in the presence or absence of type I JAK inhibitors CYT387 or BMS911543, or SAR302503 or Ruxolitinib. In the presence of inhibitors cells acquire an adaptive form of drug resistance and are here called "inhibitor persistent cells". thomas.radimerski@novartis.com,leviner@mskcc.org Accepted 2017-JUL-27 AT 17:37 BST AT 17:37 BST by PPORRAS Cancer cell 2015 Only protein-protein interactions imex curation imex curation CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibitor Persistence and Demonstrates Efficacy in Myeloproliferative Neoplasms. CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibitor Persistence and Demonstrates Efficacy in Myeloproliferative Neoplasms. Cancer cell 2015 imex curation Meyer SC., Keller MD., Chiu S., Koppikar P., Guryanova OA., Rapaport F., Xu K., Manova K., Pankov D., O'Reilly RJ., Kleppe M., McKenney AS., Shih AH., Shank K., Ahn J., Papalexi E., Spitzer B., Socci N., Viale A., Mandon E., Ebel N., Andraos R., Rubert J., Dammassa E., Romanet V., Dölemeyer A., Zender M., Heinlein M., Rampal R., Weinberg RS., Hoffman R., Sellers WR., Hofmann F., Murakami M., Baffert F., Gaul C., Radimerski T., Levine RL. Cancer - Interactions investigated in the context of cancer thomas.radimerski@novartis.com,leviner@mskcc.org 05-Sep-2017: Contacted by IntAct-Help. Only protein-protein interactions imex curation human-gamma2a Human fibroblasts lacking JAK2 Human gamma2a Human fibroblasts lacking JAK2 anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Meyer SC., Keller MD., Chiu S., Koppikar P., Guryanova OA., Rapaport F., Xu K., Manova K., Pankov D., O'Reilly RJ., Kleppe M., McKenney AS., Shih AH., Shank K., Ahn J., Papalexi E., Spitzer B., Socci N., Viale A., Mandon E., Ebel N., Andraos R., Rubert J., Dammassa E., Romanet V., Dölemeyer A., Zender M., Heinlein M., Rampal R., Weinberg RS., Hoffman R., Sellers WR., Hofmann F., Murakami M., Baffert F., Gaul C., Radimerski T., Levine RL. Cancer - Interactions investigated in the context of cancer thomas.radimerski@novartis.com,leviner@mskcc.org Accepted 2017-JUL-27 AT 17:37 BST AT 17:37 BST by PPORRAS Cancer cell 2015 Only protein-protein interactions imex curation imex curation CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibitor Persistence and Demonstrates Efficacy in Myeloproliferative Neoplasms. CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibitor Persistence and Demonstrates Efficacy in Myeloproliferative Neoplasms. Cancer cell 2015 imex curation Meyer SC., Keller MD., Chiu S., Koppikar P., Guryanova OA., Rapaport F., Xu K., Manova K., Pankov D., O'Reilly RJ., Kleppe M., McKenney AS., Shih AH., Shank K., Ahn J., Papalexi E., Spitzer B., Socci N., Viale A., Mandon E., Ebel N., Andraos R., Rubert J., Dammassa E., Romanet V., Dölemeyer A., Zender M., Heinlein M., Rampal R., Weinberg RS., Hoffman R., Sellers WR., Hofmann F., Murakami M., Baffert F., Gaul C., Radimerski T., Levine RL. Cancer - Interactions investigated in the context of cancer thomas.radimerski@novartis.com,leviner@mskcc.org 05-Sep-2017: Contacted by IntAct-Help. Only protein-protein interactions imex curation human-set2 SET2 - Human acute leukemia cell line (megakaryoblastic) set2 SET2 Human acute leukemia cell line (megakaryoblastic) confocal microscopy confocal microscopy immunocytochemistry immunocytochemistry Meyer SC., Keller MD., Chiu S., Koppikar P., Guryanova OA., Rapaport F., Xu K., Manova K., Pankov D., O'Reilly RJ., Kleppe M., McKenney AS., Shih AH., Shank K., Ahn J., Papalexi E., Spitzer B., Socci N., Viale A., Mandon E., Ebel N., Andraos R., Rubert J., Dammassa E., Romanet V., Dölemeyer A., Zender M., Heinlein M., Rampal R., Weinberg RS., Hoffman R., Sellers WR., Hofmann F., Murakami M., Baffert F., Gaul C., Radimerski T., Levine RL. Cancer - Interactions investigated in the context of cancer Cells were grown in the presence and absence of type I JAK inhibitors CYT387 or ruxolitinib. In the presence of inhibitors cells acquire an adaptive form of drug resistance and are here called "inhibitor persistent cells". thomas.radimerski@novartis.com,leviner@mskcc.org Accepted 2017-JUL-27 AT 17:37 BST AT 17:37 BST by PPORRAS Cancer cell 2015 Only protein-protein interactions imex curation imex curation jak1_human Tyrosine-protein kinase JAK1 JAK1 JAK1A JAK1B Janus kinase 1 protein protein human Homo sapiens Human MQYLNIKEDCNAMAFCAKMRSSKKTEVNLEAPEPGVEVIFYLSDREPLRLGSGEYTAEELCIRAAQACRISPLCHNLFALYDENTKLWYAPNRTITVDDKMSLRLHYRMRFYFTNWHGTNDNEQSVWRHSPKKQKNGYEKKKIPDATPLLDASSLEYLFAQGQYDLVKCLAPIRDPKTEQDGHDIENECLGMAVLAISHYAMMKKMQLPELPKDISYKRYIPETLNKSIRQRNLLTRMRINNVFKDFLKEFNNKTICDSSVSTHDLKVKYLATLETLTKHYGAEIFETSMLLISSENEMNWFHSNDGGNVLYYEVMVTGNLGIQWRHKPNVVSVEKEKNKLKRKKLENKHKKDEEKNKIREEWNNFSYFPEITHIVIKESVVSINKQDNKKMELKLSSHEEALSFVSLVDGYFRLTADAHHYLCTDVAPPLIVHNIQNGCHGPICTEYAINKLRQEGSEEGMYVLRWSCTDFDNILMTVTCFEKSEQVQGAQKQFKNFQIEVQKGRYSLHGSDRSFPSLGDLMSHLKKQILRTDNISFMLKRCCQPKPREISNLLVATKKAQEWQPVYPMSQLSFDRILKKDLVQGEHLGRGTRTHIYSGTLMDYKDDEGTSEEKKIKVILKVLDPSHRDISLAFFEAASMMRQVSHKHIVYLYGVCVRDVENIMVEEFVEGGPLDLFMHRKSDVLTTPWKFKVAKQLASALSYLEDKDLVHGNVCTKNLLLAREGIDSECGPFIKLSDPGIPITVLSRQECIERIPWIAPECVEDSKNLSVAADKWSFGTTLWEICYNGEIPLKDKTLIEKERFYESRCRPVTPSCKELADLMTRCMNYDPNQRPFFRAIMRDINKLEEQNPDIVSEKKPATEVDPTHFEKRFLKRIRDLGEGHFGKVELCRYDPEGDNTGEQVAVKSLKPESGGNHIADLKKEIEILRNLYHENIVKYKGICTEDGGNGIKLIMEFLPSGSLKEYLPKNKNKINLKQQLKYAVQICKGMDYLGSRQYVHRDLAARNVLVESEHQVKIGDFGLTKAIETDKEYYTVKDDRDSPVFWYAPECLMQSKFYIASDVWSFGVTLHELLTYCDSDSSPMALFLKMIGPTHGQMTVTRLVNTLKEGKRLPCPPNCPDEVYQLMRKCWEFQPSNRTSFQNLIEGFEALLK DIP protein P23458 original sequence version: 120 A2C4BE27851ACABB jak2_human Tyrosine-protein kinase JAK2 Janus kinase 2 JAK2 protein protein human Homo sapiens Human MGMACLTMTEMEGTSTSSIYQNGDISGNANSMKQIDPVLQVYLYHSLGKSEADYLTFPSGEYVAEEICIAASKACGITPVYHNMFALMSETERIWYPPNHVFHIDESTRHNVLYRIRFYFPRWYCSGSNRAYRHGISRGAEAPLLDDFVMSYLFAQWRHDFVHGWIKVPVTHETQEECLGMAVLDMMRIAKENDQTPLAIYNSISYKTFLPKCIRAKIQDYHILTRKRIRYRFRRFIQQFSQCKATARNLKLKYLINLETLQSAFYTEKFEVKEPGSGPSGEEIFATIIITGNGGIQWSRGKHKESETLTEQDLQLYCDFPNIIDVSIKQANQEGSNESRVVTIHKQDGKNLEIELSSLREALSFVSLIDGYYRLTADAHHYLCKEVAPPAVLENIQSNCHGPISMDFAISKLKKAGNQTGLYVLRCSPKDFNKYFLTFAVERENVIEYKHCLITKNENEEYNLSGTKKNFSSLKDLLNCYQMETVRSDNIIFQFTKCCPPKPKDKSNLLVFRTNGVSDVPTSPTLQRPTHMNQMVFHKIRNEDLIFNESLGQGTFTKIFKGVRREVGDYGQLHETEVLLKVLDKAHRNYSESFFEAASMMSKLSHKHLVLNYGVCVCGDENILVQEFVKFGSLDTYLKKNKNCINILWKLEVAKQLAWAMHFLEENTLIHGNVCAKNILLIREEDRKTGNPPFIKLSDPGISITVLPKDILQERIPWVPPECIENPKNLNLATDKWSFGTTLWEICSGGDKPLSALDSQRKLQFYEDRHQLPAPKWAELANLINNCMDYEPDFRPSFRAIIRDLNSLFTPDYELLTENDMLPNMRIGALGFSGAFEDRDPTQFEERHLKFLQQLGKGNFGSVEMCRYDPLQDNTGEVVAVKKLQHSTEEHLRDFEREIEILKSLQHDNIVKYKGVCYSAGRRNLKLIMEYLPYGSLRDYLQKHKERIDHIKLLQYTSQICKGMEYLGTKRYIHRDLATRNILVENENRVKIGDFGLTKVLPQDKEYYKVKEPGESPIFWYAPESLTESKFSVASDVWSFGVVLYELFTYIEKSKSPPAEFMRMIGNDKQGQMIVFHLIELLKNNGRLPRPDGCPDEIYMIMTECWNNNVNQRPSFRDLALRVDQIRDNMAG DIP protein O60674 original sequence version: 119 DIP protein O60674 original sequence version: 126 DIP protein O60674 original sequence version: 137 DIP protein O60674 original sequence version: 129 C30669EF1A7DA80C tyk2_human Non-receptor tyrosine-protein kinase TYK2 TYK2 protein protein human Homo sapiens Human MPLRHWGMARGSKPVGDGAQPMAAMGGLKVLLHWAGPGGGEPWVTFSESSLTAEEVCIHIAHKVGITPPCFNLFALFDAQAQVWLPPNHILEIPRDASLMLYFRIRFYFRNWHGMNPREPAVYRCGPPGTEASSDQTAQGMQLLDPASFEYLFEQGKHEFVNDVASLWELSTEEEIHHFKNESLGMAFLHLCHLALRHGIPLEEVAKKTSFKDCIPRSFRRHIRQHSALTRLRLRNVFRRFLRDFQPGRLSQQMVMVKYLATLERLAPRFGTERVPVCHLRLLAQAEGEPCYIRDSGVAPTDPGPESAAGPPTHEVLVTGTGGIQWWPVEEEVNKEEGSSGSSGRNPQASLFGKKAKAHKAVGQPADRPREPLWAYFCDFRDITHVVLKEHCVSIHRQDNKCLELSLPSRAAALSFVSLVDGYFRLTADSSHYLCHEVAPPRLVMSIRDGIHGPLLEPFVQAKLRPEDGLYLIHWSTSHPYRLILTVAQRSQAPDGMQSLRLRKFPIEQQDGAFVLEGWGRSFPSVRELGAALQGCLLRAGDDCFSLRRCCLPQPGETSNLIIMRGARASPRTLNLSQLSFHRVDQKEITQLSHLGQGTRTNVYEGRLRVEGSGDPEEGKMDDEDPLVPGRDRGQELRVVLKVLDPSHHDIALAFYETASLMSQVSHTHLAFVHGVCVRGPENIMVTEYVEHGPLDVWLRRERGHVPMAWKMVVAQQLASALSYLENKNLVHGNVCGRNILLARLGLAEGTSPFIKLSDPGVGLGALSREERVERIPWLAPECLPGGANSLSTAMDKWGFGATLLEICFDGEAPLQSRSPSEKEHFYQRQHRLPEPSCPQLATLTSQCLTYEPTQRPSFRTILRDLTRLQPHNLADVLTVNPDSPASDPTVFHKRYLKKIRDLGEGHFGKVSLYCYDPTNDGTGEMVAVKALKADCGPQHRSGWKQEIDILRTLYHEHIIKYKGCCEDQGEKSLQLVMEYVPLGSLRDYLPRHSIGLAQLLLFAQQICEGMAYLHAQHYIHRDLAARNVLLDNDRLVKIGDFGLAKAVPEGHEYYRVREDGDSPVFWYAPECLKEYKFYYASDVWSFGVTLYELLTHCDSSQSPPTKFLELIGIAQGQMTVLRLTELLERGERLPRPDKCPCEVYHLMKNCWETEASFRPTFENLIPILKTVHEKYQGQAPSVFSVC DIP protein P29597 original sequence version: 155 F76C25D6A919EDBC jak1-jak2-1 1 5 unspecified role unspecified role prey prey phosres phosres phosphorylated residue PhosRes Phospho Phosphorylation Phosphorylation (O of Serine, Threonine, Tyrosine and Aspartate, N epsilon of Lysine) undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined observed-ptm observed-ptm observed ptm observed-ptm 4 unspecified role unspecified role bait bait physical association physical association Supp 1 J/K, 3 Increased association of phosphorylated JAK2 was observed in "inhibitor persistent cells". CHZ868 (CHEBI:90828) a a Type II JAK2 Inhibitor;a reduced amount of phosphorylated JAK2 was bound to JAK1 or TYK2 in persistent cell cultures. tyk2-jak2-1 1 5 unspecified role unspecified role prey prey phosres phosres phosphorylated residue PhosRes Phospho Phosphorylation Phosphorylation (O of Serine, Threonine, Tyrosine and Aspartate, N epsilon of Lysine) undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined observed-ptm observed-ptm observed ptm observed-ptm 6 unspecified role unspecified role bait bait physical association physical association Supp 1 J/K, 3 Increased association of phosphorylated JAK2 and JAK1 was observed in "inhibitor persistent cells". CHZ868 (CHEBI:90828) a a Type II JAK2 Inhibitor;a reduced amount of phosphorylated JAK2 was bound to JAK1 or TYK2 in persistent cell cultures. jak1-jak2-2 3 5 unspecified role unspecified role neutral component neutral component 4 unspecified role unspecified role neutral component neutral component colocalization colocalization Supp 1 L/N There is an increase in colocalisation in the "persistent" cells. jak1-jak2-3 1 5 unspecified role unspecified role prey prey tyr221 optyr O4'-phospho-L-tyrosine (2S)-2-amino-3-(4-phosphonooxyphenyl)propanoic acid 2-azanyl-3-(4-phosphonooxyphenyl)propanoic acid MOD_RES Phosphotyrosine O4-phosphotyrosine tyrosine phosphate 2-amino-3-(4-hydroxyphenyl)propanoic acid 4'-phosphate O4'-phospho-L-tyrosine O4'-phosphorylated L-tyrosine OPTyr Phospho Phospho Tyrosinyl Phosphorylation phosphorylationy certain certain sequence position certain certain certain sequence position certain observed-ptm observed-ptm observed ptm observed-ptm tyr1007 optyr O4'-phospho-L-tyrosine (2S)-2-amino-3-(4-phosphonooxyphenyl)propanoic acid 2-azanyl-3-(4-phosphonooxyphenyl)propanoic acid MOD_RES Phosphotyrosine O4-phosphotyrosine tyrosine phosphate 2-amino-3-(4-hydroxyphenyl)propanoic acid 4'-phosphate O4'-phospho-L-tyrosine O4'-phosphorylated L-tyrosine OPTyr Phospho Phospho Tyrosinyl Phosphorylation phosphorylationy certain certain sequence position certain certain certain sequence position certain observed-ptm observed-ptm observed ptm observed-ptm tyr1008 optyr O4'-phospho-L-tyrosine (2S)-2-amino-3-(4-phosphonooxyphenyl)propanoic acid 2-azanyl-3-(4-phosphonooxyphenyl)propanoic acid MOD_RES Phosphotyrosine O4-phosphotyrosine tyrosine phosphate 2-amino-3-(4-hydroxyphenyl)propanoic acid 4'-phosphate O4'-phospho-L-tyrosine O4'-phosphorylated L-tyrosine OPTyr Phospho Phospho Tyrosinyl Phosphorylation phosphorylationy certain certain sequence position certain certain certain sequence position certain observed-ptm observed-ptm observed ptm observed-ptm 4 unspecified role unspecified role bait bait physical association physical association 3 A/B/D Increased association of phosphorylated JAK2 was observed in "inhibitor persistent cells". CHZ868 inhibited phosphorylation at Y221 (as well as Y1007/8) in type I JAK inhibitor persistent cells. CHZ868 (CHEBI:90828) a a Type II JAK2 Inhibitor;a reduced amount of phosphorylated JAK2 was bound to JAK1 or TYK2 in persistent cell cultures. tyk2-jak2-2 1 5 unspecified role unspecified role prey prey tyr1007 optyr O4'-phospho-L-tyrosine (2S)-2-amino-3-(4-phosphonooxyphenyl)propanoic acid 2-azanyl-3-(4-phosphonooxyphenyl)propanoic acid MOD_RES Phosphotyrosine O4-phosphotyrosine tyrosine phosphate 2-amino-3-(4-hydroxyphenyl)propanoic acid 4'-phosphate O4'-phospho-L-tyrosine O4'-phosphorylated L-tyrosine OPTyr Phospho Phospho Tyrosinyl Phosphorylation phosphorylationy certain certain sequence position certain certain certain sequence position certain observed-ptm observed-ptm observed ptm observed-ptm tyr1008 optyr O4'-phospho-L-tyrosine (2S)-2-amino-3-(4-phosphonooxyphenyl)propanoic acid 2-azanyl-3-(4-phosphonooxyphenyl)propanoic acid MOD_RES Phosphotyrosine O4-phosphotyrosine tyrosine phosphate 2-amino-3-(4-hydroxyphenyl)propanoic acid 4'-phosphate O4'-phospho-L-tyrosine O4'-phosphorylated L-tyrosine OPTyr Phospho Phospho Tyrosinyl Phosphorylation phosphorylationy certain certain sequence position certain certain certain sequence position certain observed-ptm observed-ptm observed ptm observed-ptm 6 unspecified role unspecified role bait bait physical association physical association 3 A/B/D Increased association of phosphorylated JAK2 and JAK1 was observed in "inhibitor persistent cells". CHZ868 inhibited phosphorylation at Y221 (as well as Y1007/8) in type I JAK inhibitor persistent cells. CHZ868 (CHEBI:90828) a a Type II JAK2 Inhibitor;a reduced amount of phosphorylated JAK2 was bound to JAK1 or TYK2 in persistent cell cultures. jak1-jak2-4 2 5 unspecified role unspecified role prey prey tyr1007 optyr O4'-phospho-L-tyrosine (2S)-2-amino-3-(4-phosphonooxyphenyl)propanoic acid 2-azanyl-3-(4-phosphonooxyphenyl)propanoic acid MOD_RES Phosphotyrosine O4-phosphotyrosine tyrosine phosphate 2-amino-3-(4-hydroxyphenyl)propanoic acid 4'-phosphate O4'-phospho-L-tyrosine O4'-phosphorylated L-tyrosine OPTyr Phospho Phospho Tyrosinyl Phosphorylation phosphorylationy certain certain sequence position certain certain certain sequence position certain observed-ptm observed-ptm observed ptm observed-ptm tyr1008 optyr O4'-phospho-L-tyrosine (2S)-2-amino-3-(4-phosphonooxyphenyl)propanoic acid 2-azanyl-3-(4-phosphonooxyphenyl)propanoic acid MOD_RES Phosphotyrosine O4-phosphotyrosine tyrosine phosphate 2-amino-3-(4-hydroxyphenyl)propanoic acid 4'-phosphate O4'-phospho-L-tyrosine O4'-phosphorylated L-tyrosine OPTyr Phospho Phospho Tyrosinyl Phosphorylation phosphorylationy certain certain sequence position certain certain certain sequence position certain observed-ptm observed-ptm observed ptm observed-ptm O60674:p.Lys882Glu mutation mutation certain certain sequence position certain certain certain sequence position certain K E Wed May 02 15:11:39 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'lys882glu' Tue Jun 30 18:56:40 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Lys882Glu' 4 unspecified role unspecified role bait bait P23458:p.Val658Phe mutation mutation certain certain sequence position certain certain certain sequence position certain V F Wed May 02 15:06:50 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'val658phe' Tue Jun 30 17:07:42 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Val658Phe' physical association physical association 3 C CHZ868 (CHEBI:90828) a a Type II JAK2 Inhibitor. CHZ868 reduced JAK1-mediated Y1007/Y1008 phosphorylation of JAK2 K882E (kinase dead)