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/ ALK Mutations Confer Differential Oncogenic Activation and Sensitivity to ALK Inhibition Therapy in Neuroblastoma. ALK Mutations Confer Differential Oncogenic Activation and Sensitivity to ALK Inhibition Therapy in Neuroblastoma. Cancer Cell 2014 imex curation 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 26-Feb-2015: Contacted by IntAct-Help. Only protein-protein interactions 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 I have entered Roles as Neutral/Enz etc.. - but maybe they should be "putative self" again? Table 3:- there is no data for the WT; ( a Km of 0.13mM is given earlier, but no experimental conditions (Km for ATP or what?) and for Table 3 they are implying effects from Km values at ~<0.3)- so have added interactors as "mutants". mlemmon@mail.med.upenn.edu, mosse@email.chop.edu Accepted 2015-JAN-21 by ORCHARD Cancer Cell 2014 Only protein-protein interactions imex curation ALK Mutations Confer Differential Oncogenic Activation and Sensitivity to ALK Inhibition Therapy in Neuroblastoma. ALK Mutations Confer Differential Oncogenic Activation and Sensitivity to ALK Inhibition Therapy in Neuroblastoma. Cancer Cell 2014 imex curation 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 26-Feb-2015: Contacted by IntAct-Help. Only protein-protein interactions 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 In Gel Kinase assay cannot be used for Interaction Detection, as a radio-label is specified; nowt is used here.... 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 Accepted 2015-JAN-21 by ORCHARD 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 0733D6C4FD212F41 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 KTEIFNKAUNYNJU-GFCCVEGCSA-N alk-1 2 3 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 tyrosine_kinase_domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain Q9UM73:p.Asp1270Gly mutation disrupting rate mutation disrupting interaction rate mutation disrupting rate certain certain sequence position certain certain certain sequence position certain D G Wed May 02 15:57:47 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'asp1270gly' Tue Jun 30 19:51:42 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Asp1270Gly' Q9UM73:p.Thr1151Met mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain T M Wed May 02 18:30:14 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'thr1151met' Tue Jun 30 18:33:06 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Thr1151Met' Q9UM73:p.Leu1196Met mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain L M Wed May 02 15:11:54 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'leu1196met' Tue Jun 30 17:53:26 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Leu1196Met' Q9UM73:p.Gly1286Arg mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain G R Wed May 02 15:08:37 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'gly1286arg' Tue Jun 30 17:28:17 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Gly1286Arg' Q9UM73:p.Gly1128Ala mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain G A Wed May 02 15:22:29 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'gly1128ala' Tue Jun 30 18:08:43 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Gly1128Ala' Q9UM73:p.Met1166Arg mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain M R Wed May 02 19:37:48 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'met1166arg' Tue Jun 30 20:16:58 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Met1166Arg' Q9UM73:p.Ile1170Asn mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain I N Wed May 02 18:27:20 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'ile1170asn' Tue Jun 30 19:02:41 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ile1170Asn' Q9UM73:p.Ile1170Ser mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain I S Wed May 02 16:41:49 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'ile1170ser' Tue Jun 30 18:21:10 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ile1170Ser' Q9UM73:p.Ile1171Asn mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain I N Wed May 02 19:36:16 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'ile1171asn' Tue Jun 30 17:27:05 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ile1171Asn' Q9UM73:p.Phe1174Leu mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain F L Wed May 02 16:33:42 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'phe1174leu' Tue Jun 30 19:47:36 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Phe1174Leu' Q9UM73:p.Phe1245Cys mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain F C Wed May 02 15:33:29 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'phe1245cys' Tue Jun 30 19:42:19 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Phe1245Cys' Q9UM73:p.Phe1245Val mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain F V Wed May 02 20:27:51 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'phe1245val' Tue Jun 30 17:37:06 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Phe1245Val' Q9UM73:p.Arg1192Pro mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain R P Wed May 02 16:16:06 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'arg1192pro' Tue Jun 30 19:09:28 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg1192Pro' Q9UM73:p.Tyr1278Ser mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain Y S Wed May 02 19:08:42 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'tyr1278ser' Tue Jun 30 17:04:23 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Tyr1278Ser' Q9UM73:p.Arg1275Gln mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain R Q Wed May 02 14:51:04 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'arg1275gln' Tue Jun 30 16:13:05 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg1275Gln' 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 true Supp Fig 1 Q9UM73 phosres alk-alk 1 3 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 activation_loop_peptide sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain chemical synthesis Chemical synthesis (Chemical synthesis) 3 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 I T Wed May 02 19:47:23 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'ile1250thr' Tue Jun 30 19:35:59 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ile1250Thr' Q9UM73:p.Ala1200Val mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain A V Wed May 02 18:29:41 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'ala1200val' Tue Jun 30 17:02:54 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ala1200Val' Q9UM73:p.Leu1204Phe mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain L F Wed May 02 17:27:16 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'leu1204phe' Tue Jun 30 18:05:27 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Leu1204Phe' Q9UM73:p.Tyr1278Ser mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain Y S Wed May 02 16:24:23 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'tyr1278ser' Tue Jun 30 20:00:44 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Tyr1278Ser' 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 tyrosine_kinase_domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain Q9UM73:p.Ile1170Ser mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain I S Wed May 02 15:50:09 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'ile1170ser' Tue Jun 30 18:09:37 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ile1170Ser' Q9UM73:p.Gly1128Ala mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain G A Wed May 02 18:07:09 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'gly1128ala' Tue Jun 30 18:30:49 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Gly1128Ala' Q9UM73:p.Ile1170Asn mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain I N Wed May 02 16:00:06 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'ile1170asn' Tue Jun 30 15:52:58 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ile1170Asn' Q9UM73:p.Phe1245Val mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain F V Wed May 02 14:49:06 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'phe1245val' Tue Jun 30 20:16:40 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Phe1245Val' Q9UM73:p.Ile1171Asn mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain I N Wed May 02 18:21:20 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'ile1171asn' Tue Jun 30 18:13:56 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ile1171Asn' Q9UM73:p.Leu1196Met mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain L M Wed May 02 18:34:41 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'leu1196met' Tue Jun 30 18:19:11 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Leu1196Met' Q9UM73:p.Asp1270Gly mutation disrupting rate mutation disrupting interaction rate mutation disrupting rate certain certain sequence position certain certain certain sequence position certain D G Wed May 02 18:12:06 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'asp1270gly' Tue Jun 30 19:47:26 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Asp1270Gly' Q9UM73:p.Gly1286Arg mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain G R Wed May 02 14:56:27 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'gly1286arg' Tue Jun 30 16:52:55 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Gly1286Arg' Q9UM73:p.Arg1192Pro mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain R P Wed May 02 17:09:40 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'arg1192pro' Tue Jun 30 19:03:50 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg1192Pro' Q9UM73:p.Thr1151Met mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain T M Wed May 02 16:42:34 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'thr1151met' Tue Jun 30 19:43:16 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Thr1151Met' Q9UM73:p.Phe1245Cys mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain F C Wed May 02 19:58:35 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'phe1245cys' Tue Jun 30 16:52:58 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Phe1245Cys' Q9UM73:p.Met1166Arg mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain M R Wed May 02 15:14:02 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'met1166arg' Tue Jun 30 16:38:34 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Met1166Arg' Q9UM73:p.Arg1231Gln mutation decreasing rate mutation decreasing interaction rate mutation decreasing rate certain certain sequence position certain certain certain sequence position certain R Q Wed May 02 16:25:46 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'arg1231gln' Tue Jun 30 18:36:05 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg1231Gln' Q9UM73:p.Ile1183Thr mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain I T Wed May 02 14:37:44 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'ile1183thr' Tue Jun 30 19:21:06 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ile1183Thr' 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 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 1 3 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 I T Wed May 02 15:15:25 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'ile1183thr' Tue Jun 30 17:49:17 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ile1183Thr' Q9UM73:p.Arg1192Pro mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain R P Wed May 02 18:40:29 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'arg1192pro' Tue Jun 30 19:59:55 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg1192Pro' Q9UM73:p.Ile1171Asn mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain I N Wed May 02 15:42:24 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'ile1171asn' Tue Jun 30 18:20:18 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ile1171Asn' Q9UM73:p.Leu1196Met mutation decreasing rate mutation decreasing interaction rate mutation decreasing rate certain certain sequence position certain certain certain sequence position certain L M Wed May 02 16:59:35 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'leu1196met' Tue Jun 30 15:37:26 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Leu1196Met' Q9UM73:p.Ile1170Ser mutation decreasing rate mutation decreasing interaction rate mutation decreasing rate certain certain sequence position certain certain certain sequence position certain I S Wed May 02 17:51:40 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'ile1170ser' Tue Jun 30 19:11:34 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ile1170Ser' Q9UM73:p.Ile1170Asn mutation decreasing rate mutation decreasing interaction rate mutation decreasing rate certain certain sequence position certain certain certain sequence position certain I N Wed May 02 19:34:08 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'ile1170asn' Tue Jun 30 18:41:32 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ile1170Asn' Q9UM73:p.Phe1245Cys mutation decreasing rate mutation decreasing interaction rate mutation decreasing rate certain certain sequence position certain certain certain sequence position certain F C Wed May 02 15:16:21 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'phe1245cys' Tue Jun 30 16:33:31 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Phe1245Cys' Q9UM73:p.Phe1245Val mutation decreasing rate mutation decreasing interaction rate mutation decreasing rate certain certain sequence position certain certain certain sequence position certain F V Wed May 02 14:25:01 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'phe1245val' Tue Jun 30 17:25:36 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Phe1245Val' Q9UM73:p.Arg1231Gln mutation decreasing rate mutation decreasing interaction rate mutation decreasing rate certain certain sequence position certain certain certain sequence position certain R Q Wed May 02 15:03:34 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'arg1231gln' Tue Jun 30 19:32:59 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg1231Gln' tyrosine_kinase_domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain Q9UM73:p.Thr1151Met mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain T M Wed May 02 19:18:18 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'thr1151met' Tue Jun 30 19:54:05 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Thr1151Met' 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 Q9UM73:p.Tyr1278Ser mutation increasing rate mutation increasing interaction rate mutation increasing rate certain certain sequence position certain certain certain sequence position certain Y S Wed May 02 19:49:39 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'tyr1278ser' Tue Jun 30 20:10:25 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Tyr1278Ser' Q9UM73:p.Leu1204Phe mutation decreasing rate mutation decreasing interaction rate mutation decreasing rate certain certain sequence position certain certain certain sequence position certain L F Wed May 02 14:30:16 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'leu1204phe' Tue Jun 30 17:25:26 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Leu1204Phe' 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 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 3 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 n_terminus biotin tag biotin tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range chemical synthesis Chemical synthesis (Chemical synthesis) phosphorylation phosphorylation reaction phosphorylation 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 1 4 inhibitor inhibitor unspecified role unspecified role chemical synthesis Chemical synthesis (Chemical synthesis) 3 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 Q9UM73:p.Ile1171Asn mutation mutation certain certain sequence position certain certain certain sequence position certain I N Wed May 02 19:57:16 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'ile1171asn' Tue Jun 30 19:42:54 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ile1171Asn' 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 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 3 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 n_terminus biotin tag biotin tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range chemical synthesis Chemical synthesis (Chemical synthesis) phosphorylation phosphorylation reaction phosphorylation Table 3-2 Q9UM73 phosres alk-alk-4 1 4 inhibitor inhibitor unspecified role unspecified role chemical synthesis Chemical synthesis (Chemical synthesis) 3 enzyme enzyme neutral component neutral component Q9UM73:p.Gly1128Ala mutation mutation certain certain sequence position certain certain certain sequence position certain G A Wed May 02 19:16:29 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'gly1128ala' Tue Jun 30 18:55:54 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Gly1128Ala' tyrosine_kinase_domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain 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 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 3 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 n_terminus biotin tag biotin tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range chemical synthesis Chemical synthesis (Chemical synthesis) phosphorylation phosphorylation reaction phosphorylation Table 3-1 Q9UM73 phosres alk-alk-5 1 3 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 Q9UM73:p.Leu1196Met mutation mutation certain certain sequence position certain certain certain sequence position certain L M Wed May 02 15:44:47 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'leu1196met' Tue Jun 30 16:37:02 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Leu1196Met' tyrosine_kinase_domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain 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 3 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 activation_loop_peptide sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain chemical synthesis Chemical synthesis (Chemical synthesis) 4 inhibitor inhibitor unspecified role unspecified role chemical synthesis Chemical synthesis (Chemical synthesis) phosphorylation phosphorylation reaction phosphorylation Table 3-3 Q9UM73 phosres alk-alk-6 1 4 inhibitor inhibitor unspecified role unspecified role chemical synthesis Chemical synthesis (Chemical synthesis) 3 enzyme enzyme neutral component neutral component Q9UM73:p.Tyr1278Ser mutation mutation certain certain sequence position certain certain certain sequence position certain Y S Wed May 02 16:08:34 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'tyr1278ser' Tue Jun 30 18:07:52 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Tyr1278Ser' tyrosine_kinase_domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain 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 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 3 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 n_terminus biotin tag biotin tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range chemical synthesis Chemical synthesis (Chemical synthesis) phosphorylation phosphorylation reaction phosphorylation Table 3-4 Q9UM73 phosres alk-alk-7 1 3 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 activation_loop_peptide sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain chemical synthesis Chemical synthesis (Chemical synthesis) 4 inhibitor inhibitor unspecified role unspecified role chemical synthesis Chemical synthesis (Chemical synthesis) 3 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 tyrosine_kinase_domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain Q9UM73:p.Phe1245Val mutation mutation certain certain sequence position certain certain certain sequence position certain F V Wed May 02 17:01:27 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'phe1245val' Tue Jun 30 18:46:53 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Phe1245Val' 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 Table 3-5 Q9UM73 phosres alk-alk-8 1 4 inhibitor inhibitor unspecified role unspecified role chemical synthesis Chemical synthesis (Chemical synthesis) 3 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 Q9UM73:p.Phe1245Cys mutation mutation certain certain sequence position certain certain certain sequence position certain F C Wed May 02 16:51:48 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'phe1245cys' Tue Jun 30 18:55:59 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Phe1245Cys' 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 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 3 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 n_terminus biotin tag biotin tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range chemical synthesis Chemical synthesis (Chemical synthesis) phosphorylation phosphorylation reaction phosphorylation Table 3-6 Q9UM73 phosres alk-alk-9 1 3 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 tyrosine_kinase_domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain Q9UM73:p.Arg1192Pro mutation mutation certain certain sequence position certain certain certain sequence position certain R P Wed May 02 14:35:18 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'arg1192pro' Tue Jun 30 16:04:46 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg1192Pro' 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 3 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 activation_loop_peptide sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain chemical synthesis Chemical synthesis (Chemical synthesis) 4 inhibitor inhibitor unspecified role unspecified role chemical synthesis Chemical synthesis (Chemical synthesis) phosphorylation phosphorylation reaction phosphorylation Table 3-7 Q9UM73 phosres alk-alk-10 1 4 inhibitor inhibitor unspecified role unspecified role chemical synthesis Chemical synthesis (Chemical synthesis) 3 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 Q9UM73:p.Met1166Arg mutation mutation certain certain sequence position certain certain certain sequence position certain M R Wed May 02 16:29:50 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'met1166arg' Tue Jun 30 17:51:43 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Met1166Arg' 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 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 3 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 n_terminus biotin tag biotin tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range chemical synthesis Chemical synthesis (Chemical synthesis) phosphorylation phosphorylation reaction phosphorylation Table 3-8 Q9UM73 phosres