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/ Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit. Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit. Science (0036-8075) 2007 imex curation Miled N., Yan Y., Hon WC., Perisic O., Zvelebil M., Inbar Y., Schneidman-Duhovny D., Wolfson HJ., Backer JM., Williams RL. Synapse - Interactions of proteins with an established role in the presynapse. Cancer - Interactions investigated in the context of cancer Multiple anomalous dispersion (MAD) data sets were collected at 100K on ESRF beamline ID14-4 using an ADSC CCD detector. rlw@mrc-lmb.cam.ac.uk,backer@aecom.yu.edu orchard Only protein-protein interactions in vitro In vitro enzymatic study enzymatic study predetermined predetermined participant predetermined Miled N., Yan Y., Hon WC., Perisic O., Zvelebil M., Inbar Y., Schneidman-Duhovny D., Wolfson HJ., Backer JM., Williams RL. Synapse - Interactions of proteins with an established role in the presynapse. Revisit if new term lipid kinase assay added. Multiple anomalous dispersion (MAD) data sets were collected at 100K on ESRF beamline ID14-4 using an ADSC CCD detector. rlw@mrc-lmb.cam.ac.uk,backer@aecom.yu.edu Accepted 2007-OCT-5 by ORCHARD. Science (0036-8075) 2007 orchard Only protein-protein interactions imex curation Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit. Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit. Science (0036-8075) 2007 imex curation Miled N., Yan Y., Hon WC., Perisic O., Zvelebil M., Inbar Y., Schneidman-Duhovny D., Wolfson HJ., Backer JM., Williams RL. Synapse - Interactions of proteins with an established role in the presynapse. Cancer - Interactions investigated in the context of cancer Multiple anomalous dispersion (MAD) data sets were collected at 100K on ESRF beamline ID14-4 using an ADSC CCD detector. rlw@mrc-lmb.cam.ac.uk,backer@aecom.yu.edu orchard Only protein-protein interactions in vitro In vitro x-ray diffraction x-ray crystallography X-ray X-ray x-ray diffraction predetermined predetermined participant predetermined Miled N., Yan Y., Hon WC., Perisic O., Zvelebil M., Inbar Y., Schneidman-Duhovny D., Wolfson HJ., Backer JM., Williams RL. Synapse - Interactions of proteins with an established role in the presynapse. Multiple anomalous dispersion (MAD) data sets were collected at 100K on ESRF beamline ID14-4 using an ADSC CCD detector. rlw@mrc-lmb.cam.ac.uk,backer@aecom.yu.edu Accepted 2007-OCT-5 by ORCHARD. Science (0036-8075) 2007 orchard Only protein-protein interactions imex curation pk3ca_bovin Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Phosphoinositide-3-kinase catalytic alpha polypeptide Serine/threonine protein kinase PIK3CA PIK3CA Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit alpha protein protein bovin Bos taurus (Bovine) Bovine MPPRPSSGELWGIHLMPPRILVECLLPNGMIVTLECLREATLITIKHELFKEARKYPLHQLLQDESSYIFVSVTQEAEREEFFDETRRLCDLRLFQPFLKVIEPVGNREEKILNREIGFAIGMPVCEFDMVKDPEVQDFRRNILNVCKEAVDLRDLNSPHSRAMYVYPPNVESSPELPKHIYNKLDKGQIIVVIWVIVSPNNDKQKYTLKINHDCVPEQVIAEAIRKKTRSMLLSSEQLKLCVLEYQGKYILKVCGCDEYFLEKYPLSQYKYIRSCIMLGRMPNLMLMAKESLYSQLPMDCFTMPSYSRRISTATPYMNGETSTKSLWVINSALRIKILCATYVNVNIRDIDKIYVRTGIYHGGEPLCDNVNTQRVPCSNPRWNEWLNYDIYIPDLPRAARLCLSICSVKGRKGAKEEHCPLAWGNINLFDYTDTLVSGKMALNLWPVPHGLEDLLNPIGVTGSNPNKETPCLELEFDWFSSVVKFPDMSVIEEHANWSVSREAGFSYSHAGLSNRLARDNELRENDKEQLRAICTRDPLSEITEQEKDFLWSHRHYCVTIPEILPKLLLSVKWNSRDEVAQMYCLVKDWPPIKPEQAMELLDCNYPDPMVRGFAVRCLEKYLTDDKLSQYLIQLVQVLKYEQYLDNLLVRFLLKKALTNQRIGHFFFWHLKSEMHNKTVSQRFGLLLESYCRACGMYLKHLNRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQMRRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSSAKRPLWLNWENPDIMSELLFQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHTIMQIQCKGGLKGALQFNSHTLHQWLKDKNKGEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGHFLDHKKKKFGYKRERVPFVLTQDFLIVISKGAQECTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQSFDDIAYIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQHALN DIP protein P32871 original sequence version: 93 C753DCC2F39FDDF0 p85a_human Phosphatidylinositol 3-kinase regulatory subunit alpha PIK3R1 GRB1 Phosphatidylinositol 3-kinase 85 kDa regulatory subunit alpha protein protein human Homo sapiens Human MSAEGYQYRALYDYKKEREEDIDLHLGDILTVNKGSLVALGFSDGQEARPEEIGWLNGYNETTGERGDFPGTYVEYIGRKKISPPTPKPRPPRPLPVAPGSSKTEADVEQQALTLPDLAEQFAPPDIAPPLLIKLVEAIEKKGLECSTLYRTQSSSNLAELRQLLDCDTPSVDLEMIDVHVLADAFKRYLLDLPNPVIPAAVYSEMISLAPEVQSSEEYIQLLKKLIRSPSIPHQYWLTLQYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLFRFSAASSDNTENLIKVIEILISTEWNERQPAPALPPKPPKPTTVANNGMNNNMSLQDAEWYWGDISREEVNEKLRDTADGTFLVRDASTKMHGDYTLTLRKGGNNKLIKIFHRDGKYGFSDPLTFSSVVELINHYRNESLAQYNPKLDVKLLYPVSKYQQDQVVKEDNIEAVGKKLHEYNTQFQEKSREYDRLYEEYTRTSQEIQMKRTAIEAFNETIKIFEEQCQTQERYSKEYIEKFKREGNEKEIQRIMHNYDKLKSRISEIIDSRRRLEEDLKKQAAEYREIDKRMNSIKPDLIQLRKTRDQYLMWLTQKGVRQKKLNEWLGNENTEDQYSLVEDDEDLPHHDEKTWNVGSSNRNKAENLLRGKRDGTFLVRESSKQGCYACSVVVDGEVKHCVINKTATGYGFAEPYNLYSSLKELVLHYQHTSLVQHNDSLNVTLAYPVYAQQRR DIP protein P27986 original sequence version: 181 DIP protein P27986 original sequence version: 184 DIP protein P27986-1 original sequence version: 135 DIP protein P27986 original sequence version: 135 DIP protein P27986-1 original sequence version: 145 DIP protein P27986-1 original sequence version: 147 DIP protein P27986 original sequence version: 191 B9DAD8416C33140F 1-phosphatidyl-1d-myo-inositol 1-phosphatidyl-1D-myo-inositols small molecule small molecule chemical synthesis Chemical synthesis (Chemical synthesis) pik3ca-pik3r1-5 2 4 unspecified role unspecified role neutral component neutral component arg534 binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain glu496 binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain region iSH2 domain sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain ecoli Escherichia coli (strain K12) 3 unspecified role unspecified role neutral component neutral component arg79 binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain n-terminal ABD sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain glu23 binding region binding-associated region binding region certain certain sequence position certain certain certain sequence position certain ecoli Escherichia coli (strain K12) 8 14 12 9 direct interaction direct interaction We determined the crystal structure of a complex between the bovine p110a ABD (residues 1 to 108) and the human p85a iSH2 domain (residues 431 to 600) at 2.4 A resolution 1, 2, Table S1 2.4 A working 23.3%, free 29.2% pik3ca-1_phosphat-1 1 4 inhibitor inhibitor unspecified role unspecified role region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain ecoli Escherichia coli (strain K12) 5 enzyme target enzyme target substrate substrate unspecified role unspecified role 3 enzyme enzyme unspecified role unspecified role region myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined P32871:p.Glu542Lys mutation increasing mutation increasing interaction mutation increasing mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain E K Wed May 02 14:46:05 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'glu542lys' Tue Jun 30 18:27:57 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Glu542Lys' P32871:p.Glu545Lys mutation increasing mutation increasing interaction mutation increasing mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain E K Wed May 02 17:13:46 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'glu545lys' Tue Jun 30 19:57:51 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Glu545Lys' P32871:p.Gln546Lys mutation increasing mutation increasing interaction mutation increasing mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain Q K Wed May 02 15:38:16 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'gln546lys' Tue Jun 30 16:29:34 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Gln546Lys' human-293 Homo sapiens transformed primary embryonal kidney cells Human 293 Transformed human primary embryonal kidney cells. The Cell type named 293 is synonymous with HEK-293. enzymatic reaction enzymatic reaction Biochemical reaction Biochemical reaction 3 A, D, S3 B These mutations in p110alpha blocked inhibition of kinase activity by p85ni. Binding of IRS-1 phosphotyrosine peptide (from the Tyr608/Tyr628 region) activates wild-type p110alpha/p85ni but not p110-E545K/p85ni. pik3ca-1_phosphat-8 1 5 enzyme target enzyme target substrate substrate unspecified role unspecified role 3 enzyme enzyme unspecified role unspecified role region myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 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 4 inhibitor inhibitor unspecified role unspecified role region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain P27986:p.Arg340Glu mutation disrupting mutation disrupting interaction mutation disrupting mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain R E Wed May 02 14:53:54 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'arg340glu' Tue Jun 30 16:23:06 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg340Glu' P27986:p.Lys379Glu mutation disrupting mutation disrupting interaction mutation disrupting mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain K E Wed May 02 18:07:06 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'lys379glu' Tue Jun 30 17:12:20 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Lys379Glu' ecoli Escherichia coli (strain K12) enzymatic reaction enzymatic reaction Biochemical reaction Biochemical reaction 3 B, C These mutations in p85alpha disrupt its ability to act as an inhibitor of lipid kinase activity of p110alpha. The loss of inhibition for R340E and K379E suggests that these residues are involved in an inhibitory contact with p110alpha. pik3ca-1_phosphat-2 1 4 inhibitor inhibitor unspecified role unspecified role region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain P27986:p.Lys379Glu mutation increasing mutation increasing interaction mutation increasing mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain K E Wed May 02 16:45:56 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'lys379glu' Tue Jun 30 18:42:13 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Lys379Glu' ecoli Escherichia coli (strain K12) 5 enzyme target enzyme target substrate substrate unspecified role unspecified role 3 enzyme enzyme unspecified role unspecified role region myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined P32871:p.Glu545Lys mutation mutation mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain E K Wed May 02 20:31:39 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'glu545lys' Tue Jun 30 17:15:15 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Glu545Lys' 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 enzymatic reaction enzymatic reaction Biochemical reaction Biochemical reaction 3 C The loss of inhibition for R340E and K379E suggests that these residues are involved in an inhibitory contact with the catalytic subunit. Consistent with this, the p85ni-K379E mutant inhibits the p110a-E545K oncogenic mutant, whereas the wildtype p85ni does not, suggesting that the charge reversal has reestablished the critical inhibitory interaction. pik3ca-1_phosphat-3 1 5 enzyme target enzyme target substrate substrate unspecified role unspecified role 3 enzyme enzyme unspecified role unspecified role region myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined human-293 Homo sapiens transformed primary embryonal kidney cells Human 293 Transformed human primary embryonal kidney cells. The Cell type named 293 is synonymous with HEK-293. enzymatic reaction enzymatic reaction Biochemical reaction Biochemical reaction 3 C