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/ bresler-2014-2 ALK Mutations Confer Differential Oncogenic Activation and Sensitivity to ALK Inhibition Therapy in Neuroblastoma. in vitro In vitro protein kinase assay protein kinase assay tag visualisation tag visualisation Bresler SC, Weiser DA, Huwe PJ, Park JH, Krytska K, Ryles H, Laudenslager M, Rappaport EF, Wood AC, McGrady PW, Hogarty MD, London WB, Radhakrishnan R, Lemmon MA, Mossé YP. Cancer - Interactions investigated in the context of cancer mlemmon@mail.med.upenn.edu, mosse@email.chop.edu Cancer Cell 2014 Only protein-protein interactions imex curation bresler-2014-1 ALK Mutations Confer Differential Oncogenic Activation and Sensitivity to ALK Inhibition Therapy in Neuroblastoma. in vitro In vitro protein kinase assay protein kinase assay predetermined predetermined participant predetermined Bresler SC, Weiser DA, Huwe PJ, Park JH, Krytska K, Ryles H, Laudenslager M, Rappaport EF, Wood AC, McGrady PW, Hogarty MD, London WB, Radhakrishnan R, Lemmon MA, Mossé YP. Cancer - Interactions investigated in the context of cancer Native gel Kinase assay: autophosphorylated species are detected by the presence of distinct migration bands corresponding to different phosphorylation states of ALK-TKD. Bands are shown by Coomassie blue staining. Prior to use, ALK-TKD was phosphatase treated to reverse spontaneous autophosphorylation arising during production. mlemmon@mail.med.upenn.edu, mosse@email.chop.edu Cancer Cell 2014 Only protein-protein interactions imex curation alk_human ALK tyrosine kinase receptor ALK Anaplastic lymphoma kinase protein protein human Homo sapiens Human MGAIGLLWLLPLLLSTAAVGSGMGTGQRAGSPAAGPPLQPREPLSYSRLQRKSLAVDFVVPSLFRVYARDLLLPPSSSELKAGRPEARGSLALDCAPLLRLLGPAPGVSWTAGSPAPAEARTLSRVLKGGSVRKLRRAKQLVLELGEEAILEGCVGPPGEAAVGLLQFNLSELFSWWIRQGEGRLRIRLMPEKKASEVGREGRLSAAIRASQPRLLFQIFGTGHSSLESPTNMPSPSPDYFTWNLTWIMKDSFPFLSHRSRYGLECSFDFPCELEYSPPLHDLRNQSWSWRRIPSEEASQMDLLDGPGAERSKEMPRGSFLLLNTSADSKHTILSPWMRSSSEHCTLAVSVHRHLQPSGRYIAQLLPHNEAAREILLMPTPGKHGWTVLQGRIGRPDNPFRVALEYISSGNRSLSAVDFFALKNCSEGTSPGSKMALQSSFTCWNGTVLQLGQACDFHQDCAQGEDESQMCRKLPVGFYCNFEDGFCGWTQGTLSPHTPQWQVRTLKDARFQDHQDHALLLSTTDVPASESATVTSATFPAPIKSSPCELRMSWLIRGVLRGNVSLVLVENKTGKEQGRMVWHVAAYEGLSLWQWMVLPLLDVSDRFWLQMVAWWGQGSRAIVAFDNISISLDCYLTISGEDKILQNTAPKSRNLFERNPNKELKPGENSPRQTPIFDPTVHWLFTTCGASGPHGPTQAQCNNAYQNSNLSVEVGSEGPLKGIQIWKVPATDTYSISGYGAAGGKGGKNTMMRSHGVSVLGIFNLEKDDMLYILVGQQGEDACPSTNQLIQKVCIGENNVIEEEIRVNRSVHEWAGGGGGGGGATYVFKMKDGVPVPLIIAAGGGGRAYGAKTDTFHPERLENNSSVLGLNGNSGAAGGGGGWNDNTSLLWAGKSLQEGATGGHSCPQAMKKWGWETRGGFGGGGGGCSSGGGGGGYIGGNAASNNDPEMDGEDGVSFISPLGILYTPALKVMEGHGEVNIKHYLNCSHCEVDECHMDPESHKVICFCDHGTVLAEDGVSCIVSPTPEPHLPLSLILSVVTSALVAALVLAFSGIMIVYRRKHQELQAMQMELQSPEYKLSKLRTSTIMTDYNPNYCFAGKTSSISDLKEVPRKNITLIRGLGHGAFGEVYEGQVSGMPNDPSPLQVAVKTLPEVCSEQDELDFLMEALIISKFNHQNIVRCIGVSLQSLPRFILLELMAGGDLKSFLRETRPRPSQPSSLAMLDLLHVARDIACGCQYLEENHFIHRDIAARNCLLTCPGPGRVAKIGDFGMARDIYRASYYRKGGCAMLPVKWMPPEAFMEGIFTSKTDTWSFGVLLWEIFSLGYMPYPSKSNQEVLEFVTSGGRMDPPKNCPGPVYRIMTQCWQHQPEDRPNFAIILERIEYCTQDPDVINTALPIEYGPLVEEEEKVPVRPKDPEGVPPLLVSQQAKREEERSPAAPPPLPTTSSGKAAKKPTAAEISVRVPRGPAVEGGHVNMAFSQSNPPSELHKVHGSRNKPTSLWNPTYGSWFTEKPTKKNNPIAKKEPHDRGNLGLEGSCTVPPNVATGRLPGASLLLEPSSLTANMKEVPLFRLRHFPCGNVNYGYQQQGLPLEAATAPGAGHYEDTILKSKNSMNQPGP crizotinib crizotinib crizotinib PF 2341066 PF-2341066 3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]pyridin-2-amine small molecule small molecule chemical synthesis Chemical synthesis (Chemical synthesis) KTEIFNKAUNYNJU-GFCCVEGCSA-N alk-alk 1767737 n/a 1767739 enzyme target enzyme target substrate substrate neutral component neutral component n_terminus biotin tag biotin tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false activation_loop_peptide sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false chemical synthesis Chemical synthesis (Chemical synthesis) n/a 1767739 enzyme enzyme neutral component neutral component Q9UM73:p.Ile1250Thr mutation decreasing rate mutation decreasing interaction rate mutation decreasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Ala1200Val mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Leu1204Phe mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Tyr1278Ser mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false n_terminus his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false tyrosine_kinase_domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Ile1170Ser mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Gly1128Ala mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Ile1170Asn mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Phe1245Val mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Ile1171Asn mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Leu1196Met mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Asp1270Gly mutation disrupting rate mutation disrupting interaction rate mutation disrupting rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Gly1286Arg mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Arg1192Pro mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Thr1151Met mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Phe1245Cys mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Met1166Arg mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Arg1231Gln mutation decreasing rate mutation decreasing interaction rate mutation decreasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Ile1183Thr mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false spofr-sf_9 Spodoptera frugiperda insect cells Fall armyworm sf_9 insect cells Derived from pupal ovarian tissue of the fall armyworm Cloned from the parent cell line, IPLB-SF-21-AE (SF-21) derived from immature ovaries of fall armyworm Spodoptera frugiperda pupae cells are susceptible to Baculovirus infection phosphorylation phosphorylation reaction phosphorylation false false false 1767737 Fig 3A/B, Supp table 4. Supp fig 2. Q9UM73 phosres For these nonphosphorylated ALK TKD variants, the Wild-type and R1275Q, F1174L activating mutations were previously tested. F1174 and F1245 mutations have the strongest effect, increasing the kcat 36- to 39-fold, close to the 45-fold increase caused by autophosphorylation of the wild-type ALK TKD. Catalytic efficiencies (kcat/Km, ATP and kcat/Km peptide) for nonphosphorylated ALK TKD variants (Figure S2A) follow very similar trends as those seen for the kcat. alk-alk-1 1767737 n/a 1767739 enzyme enzyme neutral component neutral component Q9UM73:p.Ile1183Thr mutation decreasing rate mutation decreasing interaction rate mutation decreasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Arg1192Pro mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Ile1171Asn mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Leu1196Met mutation decreasing rate mutation decreasing interaction rate mutation decreasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Ile1170Ser mutation decreasing rate mutation decreasing interaction rate mutation decreasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Ile1170Asn mutation decreasing rate mutation decreasing interaction rate mutation decreasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Phe1245Cys mutation decreasing rate mutation decreasing interaction rate mutation decreasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Phe1245Val mutation decreasing rate mutation decreasing interaction rate mutation decreasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Arg1231Gln mutation decreasing rate mutation decreasing interaction rate mutation decreasing rate certain certain sequence position certain certain certain sequence position certain false tyrosine_kinase_domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Thr1151Met mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false required_phosphores 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 false Q9UM73:p.Tyr1278Ser mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Leu1204Phe mutation decreasing rate mutation decreasing interaction rate mutation decreasing rate certain certain sequence position certain certain certain sequence position certain false n_terminus his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false spofr-sf_9 Spodoptera frugiperda insect cells Fall armyworm sf_9 insect cells Derived from pupal ovarian tissue of the fall armyworm Cloned from the parent cell line, IPLB-SF-21-AE (SF-21) derived from immature ovaries of fall armyworm Spodoptera frugiperda pupae cells are susceptible to Baculovirus infection n/a 1767739 enzyme target enzyme target substrate substrate neutral component neutral component activation_loop_peptide sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false n_terminus biotin tag biotin tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false chemical synthesis Chemical synthesis (Chemical synthesis) phosphorylation phosphorylation reaction phosphorylation false false false 1767737 Fig 3C, Supp table 5 Q9UM73 phosres For these phosphorylated ALK TKD variants, the Wild-type and R1275Q activating mutation were previously tested. The effects of patient-derived ALK mutations on the activity of the fully autophosphorylated ALK TKD were much more modest than those seen using non-phosphorylated forms; no variant was altered more than 2-fold in Kcat. alk-alk-3 1767737 n/a 1767740 inhibitor inhibitor unspecified role unspecified role chemical synthesis Chemical synthesis (Chemical synthesis) n/a 1767739 enzyme enzyme neutral component neutral component tyrosine_kinase_domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Ile1171Asn mutation mutation certain certain sequence position certain certain certain sequence position certain false n_terminus his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false spofr-sf_9 Spodoptera frugiperda insect cells Fall armyworm sf_9 insect cells Derived from pupal ovarian tissue of the fall armyworm Cloned from the parent cell line, IPLB-SF-21-AE (SF-21) derived from immature ovaries of fall armyworm Spodoptera frugiperda pupae cells are susceptible to Baculovirus infection n/a 1767739 enzyme target enzyme target substrate substrate neutral component neutral component activation_loop_peptide sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false n_terminus biotin tag biotin tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false chemical synthesis Chemical synthesis (Chemical synthesis) phosphorylation phosphorylation reaction phosphorylation false false false 1767737 1767737 Table 3-2 Q9UM73 phosres alk-alk-4 1767737 n/a 1767740 inhibitor inhibitor unspecified role unspecified role chemical synthesis Chemical synthesis (Chemical synthesis) n/a 1767739 enzyme enzyme neutral component neutral component Q9UM73:p.Gly1128Ala mutation mutation certain certain sequence position certain certain certain sequence position certain false tyrosine_kinase_domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false n_terminus his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false spofr-sf_9 Spodoptera frugiperda insect cells Fall armyworm sf_9 insect cells Derived from pupal ovarian tissue of the fall armyworm Cloned from the parent cell line, IPLB-SF-21-AE (SF-21) derived from immature ovaries of fall armyworm Spodoptera frugiperda pupae cells are susceptible to Baculovirus infection n/a 1767739 enzyme target enzyme target substrate substrate neutral component neutral component activation_loop_peptide sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false n_terminus biotin tag biotin tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false chemical synthesis Chemical synthesis (Chemical synthesis) phosphorylation phosphorylation reaction phosphorylation false false false 1767737 1767737 Table 3-1 Q9UM73 phosres alk-alk-5 1767737 n/a 1767739 enzyme enzyme neutral component neutral component n_terminus his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false Q9UM73:p.Leu1196Met mutation mutation certain certain sequence position certain certain certain sequence position certain false tyrosine_kinase_domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false spofr-sf_9 Spodoptera frugiperda insect cells Fall armyworm sf_9 insect cells Derived from pupal ovarian tissue of the fall armyworm Cloned from the parent cell line, IPLB-SF-21-AE (SF-21) derived from immature ovaries of fall armyworm Spodoptera frugiperda pupae cells are susceptible to Baculovirus infection n/a 1767739 enzyme target enzyme target substrate substrate neutral component neutral component n_terminus biotin tag biotin tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false activation_loop_peptide sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false chemical synthesis Chemical synthesis (Chemical synthesis) n/a 1767740 inhibitor inhibitor unspecified role unspecified role chemical synthesis Chemical synthesis (Chemical synthesis) phosphorylation phosphorylation reaction phosphorylation false false false 1767737 1767737 Table 3-3 Q9UM73 phosres alk-alk-6 1767737 n/a 1767740 inhibitor inhibitor unspecified role unspecified role chemical synthesis Chemical synthesis (Chemical synthesis) n/a 1767739 enzyme enzyme neutral component neutral component Q9UM73:p.Tyr1278Ser mutation mutation certain certain sequence position certain certain certain sequence position certain false tyrosine_kinase_domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false n_terminus his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false spofr-sf_9 Spodoptera frugiperda insect cells Fall armyworm sf_9 insect cells Derived from pupal ovarian tissue of the fall armyworm Cloned from the parent cell line, IPLB-SF-21-AE (SF-21) derived from immature ovaries of fall armyworm Spodoptera frugiperda pupae cells are susceptible to Baculovirus infection n/a 1767739 enzyme target enzyme target substrate substrate neutral component neutral component activation_loop_peptide sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false n_terminus biotin tag biotin tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false chemical synthesis Chemical synthesis (Chemical synthesis) phosphorylation phosphorylation reaction phosphorylation false false false 1767737 1767737 Table 3-4 Q9UM73 phosres alk-alk-7 1767737 n/a 1767739 enzyme target enzyme target substrate substrate neutral component neutral component n_terminus biotin tag biotin tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false activation_loop_peptide sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false chemical synthesis Chemical synthesis (Chemical synthesis) n/a 1767740 inhibitor inhibitor unspecified role unspecified role chemical synthesis Chemical synthesis (Chemical synthesis) n/a 1767739 enzyme enzyme neutral component neutral component n_terminus his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false tyrosine_kinase_domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Phe1245Val mutation mutation certain certain sequence position certain certain certain sequence position certain false spofr-sf_9 Spodoptera frugiperda insect cells Fall armyworm sf_9 insect cells Derived from pupal ovarian tissue of the fall armyworm Cloned from the parent cell line, IPLB-SF-21-AE (SF-21) derived from immature ovaries of fall armyworm Spodoptera frugiperda pupae cells are susceptible to Baculovirus infection phosphorylation phosphorylation reaction phosphorylation false false false 1767737 1767737 Table 3-5 Q9UM73 phosres alk-alk-8 1767737 n/a 1767740 inhibitor inhibitor unspecified role unspecified role chemical synthesis Chemical synthesis (Chemical synthesis) n/a 1767739 enzyme enzyme neutral component neutral component tyrosine_kinase_domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Phe1245Cys mutation mutation certain certain sequence position certain certain certain sequence position certain false n_terminus his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false spofr-sf_9 Spodoptera frugiperda insect cells Fall armyworm sf_9 insect cells Derived from pupal ovarian tissue of the fall armyworm Cloned from the parent cell line, IPLB-SF-21-AE (SF-21) derived from immature ovaries of fall armyworm Spodoptera frugiperda pupae cells are susceptible to Baculovirus infection n/a 1767739 enzyme target enzyme target substrate substrate neutral component neutral component activation_loop_peptide sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false n_terminus biotin tag biotin tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false chemical synthesis Chemical synthesis (Chemical synthesis) phosphorylation phosphorylation reaction phosphorylation false false false 1767737 1767737 Table 3-6 Q9UM73 phosres alk-alk-9 1767737 n/a 1767739 enzyme enzyme neutral component neutral component n_terminus his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false tyrosine_kinase_domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Arg1192Pro mutation mutation certain certain sequence position certain certain certain sequence position certain false spofr-sf_9 Spodoptera frugiperda insect cells Fall armyworm sf_9 insect cells Derived from pupal ovarian tissue of the fall armyworm Cloned from the parent cell line, IPLB-SF-21-AE (SF-21) derived from immature ovaries of fall armyworm Spodoptera frugiperda pupae cells are susceptible to Baculovirus infection n/a 1767739 enzyme target enzyme target substrate substrate neutral component neutral component n_terminus biotin tag biotin tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false activation_loop_peptide sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false chemical synthesis Chemical synthesis (Chemical synthesis) n/a 1767740 inhibitor inhibitor unspecified role unspecified role chemical synthesis Chemical synthesis (Chemical synthesis) phosphorylation phosphorylation reaction phosphorylation false false false 1767737 1767737 Table 3-7 Q9UM73 phosres alk-alk-10 1767737 n/a 1767740 inhibitor inhibitor unspecified role unspecified role chemical synthesis Chemical synthesis (Chemical synthesis) n/a 1767739 enzyme enzyme neutral component neutral component tyrosine_kinase_domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Met1166Arg mutation mutation certain certain sequence position certain certain certain sequence position certain false n_terminus his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false spofr-sf_9 Spodoptera frugiperda insect cells Fall armyworm sf_9 insect cells Derived from pupal ovarian tissue of the fall armyworm Cloned from the parent cell line, IPLB-SF-21-AE (SF-21) derived from immature ovaries of fall armyworm Spodoptera frugiperda pupae cells are susceptible to Baculovirus infection n/a 1767739 enzyme target enzyme target substrate substrate neutral component neutral component activation_loop_peptide sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false n_terminus biotin tag biotin tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false chemical synthesis Chemical synthesis (Chemical synthesis) phosphorylation phosphorylation reaction phosphorylation false false false 1767737 1767737 Table 3-8 Q9UM73 phosres alk-1 1767738 n/a 1767739 putative self putative self putative self putative self n_terminus his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false tyrosine_kinase_domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Asp1270Gly mutation disrupting rate mutation disrupting interaction rate mutation disrupting rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Thr1151Met mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Leu1196Met mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Gly1286Arg mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Gly1128Ala mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Met1166Arg mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Ile1170Asn mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Ile1170Ser mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Ile1171Asn mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Phe1174Leu mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Phe1245Cys mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Phe1245Val mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Arg1192Pro mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Tyr1278Ser mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false Q9UM73:p.Arg1275Gln mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain false spofr-sf_9 Spodoptera frugiperda insect cells Fall armyworm sf_9 insect cells Derived from pupal ovarian tissue of the fall armyworm Cloned from the parent cell line, IPLB-SF-21-AE (SF-21) derived from immature ovaries of fall armyworm Spodoptera frugiperda pupae cells are susceptible to Baculovirus infection phosphorylation phosphorylation reaction phosphorylation false true false Supp Fig 1 Q9UM73 phosres