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/ papa-2014-1 Cancer-associated PTEN mutants act in a dominant-negative manner to suppress PTEN protein function. human-pc3 Human PC3 Caucasian prostate adenocarcinoma pc3 Human Caucasian prostate adenocarcinoma anti tag coip anti tag coimmunoprecipitation anti tag coip anti tag western anti tag western blot anti tag western Papa A., Wan L., Bonora M., Salmena L., Song M.S., Hobbs R.M., Lunardi A., Webster K., Ng C., Newton R.H., Knoblauch N., Guarnerio J., Ito K., Turka L.A., Beck A.H., Pinton P., Bronson R.T., Wei W., Pandolfi P.P. ppandolf@bidmc.harvard.edu Cell (0092-8674) 2014 imex curation Interactions involving components of the PI3K complex (p85:p110) were not annotated as these mapped to multiple gene products. Only protein-protein interactions papa-2014-5 Cancer-associated PTEN mutants act in a dominant-negative manner to suppress PTEN protein function. human-pc3 Human PC3 Caucasian prostate adenocarcinoma pc3 Human Caucasian prostate adenocarcinoma bret bioluminescence resonance energy transfer BRET LRET LRET BRET bret tag visualisation tag visualisation Papa A., Wan L., Bonora M., Salmena L., Song M.S., Hobbs R.M., Lunardi A., Webster K., Ng C., Newton R.H., Knoblauch N., Guarnerio J., Ito K., Turka L.A., Beck A.H., Pinton P., Bronson R.T., Wei W., Pandolfi P.P. Administration of Coelenterazine as substrate for the luciferase induced Renilla excitation that generated a BRET signal when in proximity to the GFP ppandolf@bidmc.harvard.edu Cell (0092-8674) 2014 imex curation Interactions involving components of the PI3K complex (p85:p110) were not annotated as these mapped to multiple gene products. Only protein-protein interactions papa-2014-2 Cancer-associated PTEN mutants act in a dominant-negative manner to suppress PTEN protein function. human-293t Homo sapiens 293 cells transformed with SV40 large T antigen 293t 293 cells expressing SV40 large T antigen. The original designation of this cell line was 293tsA1609neo. It is not in Cabri,ATCC or HyperCLDB. anti tag coip anti tag coimmunoprecipitation anti tag coip western blot western blot Immuno blot Immuno blot Papa A., Wan L., Bonora M., Salmena L., Song M.S., Hobbs R.M., Lunardi A., Webster K., Ng C., Newton R.H., Knoblauch N., Guarnerio J., Ito K., Turka L.A., Beck A.H., Pinton P., Bronson R.T., Wei W., Pandolfi P.P. ppandolf@bidmc.harvard.edu Cell (0092-8674) 2014 imex curation Interactions involving components of the PI3K complex (p85:p110) were not annotated as these mapped to multiple gene products. Only protein-protein interactions papa-2014-3 Cancer-associated PTEN mutants act in a dominant-negative manner to suppress PTEN protein function. mouse-nih_3t3 Mus musculus Swiss NIH 3t3 embryo fibroblast cells nih_3t3 Mouse Swiss NIH embryo contact inhibited fibroblast cells comig non denat gel comigration in non denaturing gel electrophoresis comig non denat gel western blot western blot Immuno blot Immuno blot Papa A., Wan L., Bonora M., Salmena L., Song M.S., Hobbs R.M., Lunardi A., Webster K., Ng C., Newton R.H., Knoblauch N., Guarnerio J., Ito K., Turka L.A., Beck A.H., Pinton P., Bronson R.T., Wei W., Pandolfi P.P. PTEN protein was first immunoprecipitated before running on native gel electrophoresis. ppandolf@bidmc.harvard.edu Cell (0092-8674) 2014 imex curation Interactions involving components of the PI3K complex (p85:p110) were not annotated as these mapped to multiple gene products. Only protein-protein interactions papa-2014-4 Cancer-associated PTEN mutants act in a dominant-negative manner to suppress PTEN protein function. ecoli Escherichia coli (strain K12) pull down pull down anti tag western anti tag western blot anti tag western Papa A., Wan L., Bonora M., Salmena L., Song M.S., Hobbs R.M., Lunardi A., Webster K., Ng C., Newton R.H., Knoblauch N., Guarnerio J., Ito K., Turka L.A., Beck A.H., Pinton P., Bronson R.T., Wei W., Pandolfi P.P. ppandolf@bidmc.harvard.edu Cell (0092-8674) 2014 imex curation Interactions involving components of the PI3K complex (p85:p110) were not annotated as these mapped to multiple gene products. Only protein-protein interactions papa-2014-6 Cancer-associated PTEN mutants act in a dominant-negative manner to suppress PTEN protein function. human-pc3 Human PC3 Caucasian prostate adenocarcinoma pc3 Human Caucasian prostate adenocarcinoma comig non denat gel comigration in non denaturing gel electrophoresis comig non denat gel anti tag western anti tag western blot anti tag western Papa A., Wan L., Bonora M., Salmena L., Song M.S., Hobbs R.M., Lunardi A., Webster K., Ng C., Newton R.H., Knoblauch N., Guarnerio J., Ito K., Turka L.A., Beck A.H., Pinton P., Bronson R.T., Wei W., Pandolfi P.P. Immunoprecipitated lysates were used as an input for the gel run. ppandolf@bidmc.harvard.edu Cell (0092-8674) 2014 imex curation Interactions involving components of the PI3K complex (p85:p110) were not annotated as these mapped to multiple gene products. Only protein-protein interactions papa-2014-7 Cancer-associated PTEN mutants act in a dominant-negative manner to suppress PTEN protein function. human-pc3 Human PC3 Caucasian prostate adenocarcinoma pc3 Human Caucasian prostate adenocarcinoma comig non denat gel comigration in non denaturing gel electrophoresis comig non denat gel western blot western blot Immuno blot Immuno blot Papa A., Wan L., Bonora M., Salmena L., Song M.S., Hobbs R.M., Lunardi A., Webster K., Ng C., Newton R.H., Knoblauch N., Guarnerio J., Ito K., Turka L.A., Beck A.H., Pinton P., Bronson R.T., Wei W., Pandolfi P.P. Immunoprecipitated lysates were used as an input for the gel run. ppandolf@bidmc.harvard.edu Cell (0092-8674) 2014 imex curation Interactions involving components of the PI3K complex (p85:p110) were not annotated as these mapped to multiple gene products. Only protein-protein interactions papa-2014-8 Cancer-associated PTEN mutants act in a dominant-negative manner to suppress PTEN protein function. in vitro In vitro phosphatase assay phosphatase assay predetermined predetermined participant predetermined Papa A., Wan L., Bonora M., Salmena L., Song M.S., Hobbs R.M., Lunardi A., Webster K., Ng C., Newton R.H., Knoblauch N., Guarnerio J., Ito K., Turka L.A., Beck A.H., Pinton P., Bronson R.T., Wei W., Pandolfi P.P. Interactions involving components of the PI3K complex (p85:p110) were not annotated as these mapped to multiple gene products. ppandolf@bidmc.harvard.edu Cell (0092-8674) 2014 Only protein-protein interactions imex curation pten_human Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN Phosphatase and tensin homolog Mutated in multiple advanced cancers 1 PTEN MMAC1 TEP1 protein protein human Homo sapiens Human MTAIIKEIVSRNKRRYQEDGFDLDLTYIYPNIIAMGFPAERLEGVYRNNIDDVVRFLDSKHKNHYKIYNLCAERHYDTAKFNCRVAQYPFEDHNPPQLELIKPFCEDLDQWLSEDDNHVAAIHCKAGKGRTGVMICAYLLHRGKFLKAQEALDFYGEVRTRDKKGVTIPSQRRYVYYYSYLLKNHLDYRPVALLFHKMMFETIPMFSGGTCNPQFVVCQLKVKIYSSNSGPTRREDKFMYFEFPQPLPVCGDIKVEFFHKQNKMLKKDKMFHFWVNTFFIPGPEETSEKVENGSLCDQEIDSICSIERADNDKEYLVLTLTKNDLDKANKDKANRYFSPNFKVKLYFTKTVEEPSNPEASSSTSVTPDVSDNEPDHYRYSDTTDSDPENEPFDEDQHTQITKV pten_mouse Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN Mutated in multiple advanced cancers 1 Pten Mmac1 Phosphatase and tensin homolog protein protein mouse Mus musculus Mouse MTAIIKEIVSRNKRRYQEDGFDLDLTYIYPNIIAMGFPAERLEGVYRNNIDDVVRFLDSKHKNHYKIYNLCAERHYDTAKFNCRVAQYPFEDHNPPQLELIKPFCEDLDQWLSEDDNHVAAIHCKAGKGRTGVMICAYLLHRGKFLKAQEALDFYGEVRTRDKKGVTIPSQRRYVYYYSYLLKNHLDYRPVALLFHKMMFETIPMFSGGTCNPQFVVCQLKVKIYSSNSGPTRREDKFMYFEFPQPLPVCGDIKVEFFHKQNKMLKKDKMFHFWVNTFFIPGPEETSEKVENGSLCDQEIDSICSIERADNDKEYLVLTLTKNDLDKANKDKANRYFSPNFKVKLYFTKTVEEPSNPEASSSTSVTPDVSDNEPDHYRYSDTTDSDPENEPFDEDQHSQITKV 1-phosphatidyl-1d-myo-inositol 3,4,5-trisphosphate 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphates small molecule small molecule chemical synthesis Chemical synthesis (Chemical synthesis) pten-pten-1 1554427 n/a 1554435 unspecified role unspecified role bait bait n-terminal myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false n/a 1554435 unspecified role unspecified role prey prey n-terminal gfp tag green fluorescent protein tag GFP green fluorescent protein GFP green fluorescent protein gfp tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false physical association physical association false false false Fig. 1A, 3B, 6D, 7C, Supp. Fig. 1B, 1C, 2B PTEN uses multiple interfaces along the entire protein to dimerize pten-pten-2 1554427 n/a 1554435 unspecified role unspecified role prey prey n-terminal myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false n/a 1554435 unspecified role unspecified role bait bait n-terminal gfp tag green fluorescent protein tag GFP green fluorescent protein GFP green fluorescent protein gfp tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false physical association physical association false false false Fig. 1A pten-pten-11 1554427 n/a 1554435 unspecified role unspecified role bait bait n-terminal flag tag flag tag FLAG-tagged FLAG DYKDDDDKV epitope tag DYKDDDDKV epitope tag FLAG FLAG-tagged undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false n/a 1554435 unspecified role unspecified role prey prey n-terminal myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false physical association physical association false false false Supp. Fig. 2D PTEN uses multiple interfaces along the entire protein to dimerize pten-pten-6 1554428 n/a 1554435 proton donor proton donor neutral component neutral component region renilla luciferase renilla luciferase protein tag renilla luciferase undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false n/a 1554435 proton acceptor proton acceptor neutral component neutral component region gfp tag green fluorescent protein tag GFP green fluorescent protein GFP green fluorescent protein gfp tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false proximity proximity close-contact colocalization neighbourhood interaction false false false Fig. 1E, 1F, 1H, 3C pten-pten-7 1554428 n/a 1554435 proton donor proton donor neutral component neutral component region renilla luciferase renilla luciferase protein tag renilla luciferase undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined false n/a 1554435 competitor competitor competitor neutral component neutral component n/a 1554435 proton acceptor proton acceptor neutral component neutral component region gfp tag green fluorescent protein tag GFP green fluorescent protein GFP green fluorescent protein gfp tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false proximity proximity close-contact colocalization neighbourhood interaction false false false Fig. 1G pten-pten-3 1554429 n/a 1554435 unspecified role unspecified role bait bait n-terminal gfp tag green fluorescent protein tag GFP green fluorescent protein GFP green fluorescent protein gfp tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false n/a 1554435 unspecified role unspecified role prey prey physical association physical association false false false Fig. 1B pten-8 1554430 n/a 1554436 unspecified role unspecified role neutral component neutral component Stoichiometry: 2.0 physical association physical association false false false 1C pten-pten-4 1554431 n/a 1554435 unspecified role unspecified role bait bait n-terminal gst tag glutathione s tranferase tag glutathione S-tranferase tag glutathione S-tranferase tag gst tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false n/a 1554435 unspecified role unspecified role prey prey n-terminal 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 physical association physical association false false false Fig. 1D, 2B, 3D, 7B PTEN uses multiple interfaces along the entire protein to dimerise. pten-1 1554432 n/a 1554435 unspecified role unspecified role neutral component neutral component n-terminal myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false Stoichiometry: 2.0 physical association physical association false false false Fig. 2I, 3A Supp. Fig. 1D, 2H Point mutation and western blot data suggests phosphorylation of the C-terminal tail maintains PTEN as a monomer pten-pten-12 1554433 n/a 1554435 unspecified role unspecified role neutral component neutral component n-terminal myc tag myc tag EUKLISEED epitope tag EUKLISEED epitope tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false Stoichiometry: 2.0 physical association physical association false false false Supp. Fig. 1A 1_phosphatidyl_1d_myo_inositol_3_4_5_trisphosphate-pten-1 1554434 n/a 1554437 enzyme target enzyme target substrate substrate neutral component neutral component n/a 1554435 enzyme enzyme neutral component neutral component n-terminal gst tag glutathione s tranferase tag glutathione S-tranferase tag glutathione S-tranferase tag gst tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false P60484:p.Cys124Ser mutation decreasing rate mutation decreasing interaction rate mutation decreasing rate certain certain sequence position certain certain certain sequence position certain false P60484:p.Gly129Glu mutation decreasing rate mutation decreasing interaction rate mutation decreasing rate certain certain sequence position certain certain certain sequence position certain false P60484:p.Arg130Gly mutation decreasing rate mutation decreasing interaction rate mutation decreasing rate certain certain sequence position certain certain certain sequence position certain false ecoli Escherichia coli (strain K12) Stoichiometry: 1.0 n/a 1554435 enzyme enzyme unspecified role unspecified role n-terminal 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 ecoli Escherichia coli (strain K12) Stoichiometry: 1.0 dephosphorylation dephosphorylation reaction dephosphorylation false false false Fig. 3E, 7D