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/ A CDKN2A mutation in familial melanoma that abrogates binding of p16INK4a to CDK4 but not CDK6. A CDKN2A mutation in familial melanoma that abrogates binding of p16INK4a to CDK4 but not CDK6. Cancer Res. (0008-5472) 2007 imex curation Jones R., Ruas M., Gregory F., Moulin S., Delia D., Manoukian S., Rowe J., Brookes S., Peters G. Apoptosis - Interactions involving proteins with a function related to apoptosis Cancer - Interactions investigated in the context of cancer There are two experiments which are similar with Milan HDFs; because of different treatments I have created separate experiments with different exp-modification annotation. To enhance expression of p14ARF, cells were infected with a recombinant retrovirus encoding an ER-E2F1 fusion protein. Upon addition of 4-hydroxy tamoxifen to activate E2F1 expression, p14ARF became detectable by immunoblotting. gordon.peters@cancer.org.uk 22-Jan-2008: Contacted by JYOTI. davet Only protein-protein interactions imex curation human-milan_df Homo sapiens primary diploid skin fibroblasts homozygous for the R24P mutation in p16INK4A milan_df Human Milan diploid fibroblasts A culture of primary skin fibroblasts from a biopsy of a patient homozygous for the R24P mutation in p16INK4A anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Jones R., Ruas M., Gregory F., Moulin S., Delia D., Manoukian S., Rowe J., Brookes S., Peters G. Apoptosis - Interactions involving proteins with a function related to apoptosis There are two experiments which are similar with Milan HDFs; because of different treatments I have created separate experiments with different exp-modification annotation. To enhance expression of p14ARF, cells were infected with a recombinant retrovirus encoding an ER-E2F1 fusion protein. Upon addition of 4-hydroxy tamoxifen to activate E2F1 expression, p14ARF became detectable by immunoblotting. gordon.peters@cancer.org.uk Accepted 2007-Not a month!-13 by DAVET. 22-Jan-2008: Contacted by JYOTI. Cancer Res. (0008-5472) 2007 davet IMEx A CDKN2A mutation in familial melanoma that abrogates binding of p16INK4a to CDK4 but not CDK6. A CDKN2A mutation in familial melanoma that abrogates binding of p16INK4a to CDK4 but not CDK6. Cancer Res. (0008-5472) 2007 imex curation Jones R., Ruas M., Gregory F., Moulin S., Delia D., Manoukian S., Rowe J., Brookes S., Peters G. Apoptosis - Interactions involving proteins with a function related to apoptosis Cancer - Interactions investigated in the context of cancer There are two experiments which are similar with Milan HDFs; because of different treatments I have created separate experiments with different exp-modification annotation. To enhance expression of p14ARF, cells were infected with a recombinant retrovirus encoding an ER-E2F1 fusion protein. Upon addition of 4-hydroxy tamoxifen to activate E2F1 expression, p14ARF became detectable by immunoblotting. gordon.peters@cancer.org.uk 22-Jan-2008: Contacted by JYOTI. davet Only protein-protein interactions imex curation human-fibroblast Homo sapiens normal diploid fibroblasts (HDF0 fibroblast Fibroblast anti bait coip anti bait coimmunoprecipitation anti bait coip anti tag western anti tag western blot anti tag western Jones R., Ruas M., Gregory F., Moulin S., Delia D., Manoukian S., Rowe J., Brookes S., Peters G. Apoptosis - Interactions involving proteins with a function related to apoptosis There are two experiments which are similar with Milan diploid fibroblasts; because of different treatments I have created separate experiments with different exp-modification annotation. To enhance expression of p14ARF, cells were infected with a recombinant retrovirus encoding an ER-E2F1 fusion protein. Upon addition of 4-hydroxy tamoxifen to activate E2F1 expression, p14ARF became detectable by immunoblotting. Cells - human diploid fibroblasts gordon.peters@cancer.org.uk Accepted 2007-Not a month!-13 by DAVET. Cancer Res. (0008-5472) 2007 davet IMEx A CDKN2A mutation in familial melanoma that abrogates binding of p16INK4a to CDK4 but not CDK6. A CDKN2A mutation in familial melanoma that abrogates binding of p16INK4a to CDK4 but not CDK6. Cancer Res. (0008-5472) 2007 imex curation Jones R., Ruas M., Gregory F., Moulin S., Delia D., Manoukian S., Rowe J., Brookes S., Peters G. Apoptosis - Interactions involving proteins with a function related to apoptosis Cancer - Interactions investigated in the context of cancer There are two experiments which are similar with Milan HDFs; because of different treatments I have created separate experiments with different exp-modification annotation. To enhance expression of p14ARF, cells were infected with a recombinant retrovirus encoding an ER-E2F1 fusion protein. Upon addition of 4-hydroxy tamoxifen to activate E2F1 expression, p14ARF became detectable by immunoblotting. gordon.peters@cancer.org.uk 22-Jan-2008: Contacted by JYOTI. davet Only protein-protein interactions imex curation in vitro In vitro anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Jones R., Ruas M., Gregory F., Moulin S., Delia D., Manoukian S., Rowe J., Brookes S., Peters G. Apoptosis - Interactions involving proteins with a function related to apoptosis gordon.peters@cancer.org.uk 22-Jan-2008: Contacted by JYOTI. Cancer Res. (0008-5472) 2007 davet IMEx A CDKN2A mutation in familial melanoma that abrogates binding of p16INK4a to CDK4 but not CDK6. A CDKN2A mutation in familial melanoma that abrogates binding of p16INK4a to CDK4 but not CDK6. Cancer Res. (0008-5472) 2007 imex curation Jones R., Ruas M., Gregory F., Moulin S., Delia D., Manoukian S., Rowe J., Brookes S., Peters G. Apoptosis - Interactions involving proteins with a function related to apoptosis Cancer - Interactions investigated in the context of cancer There are two experiments which are similar with Milan HDFs; because of different treatments I have created separate experiments with different exp-modification annotation. To enhance expression of p14ARF, cells were infected with a recombinant retrovirus encoding an ER-E2F1 fusion protein. Upon addition of 4-hydroxy tamoxifen to activate E2F1 expression, p14ARF became detectable by immunoblotting. gordon.peters@cancer.org.uk 22-Jan-2008: Contacted by JYOTI. davet Only protein-protein interactions imex curation human-milan_df Homo sapiens primary diploid skin fibroblasts homozygous for the R24P mutation in p16INK4A milan_df Human Milan diploid fibroblasts A culture of primary skin fibroblasts from a biopsy of a patient homozygous for the R24P mutation in p16INK4A anti bait coip anti bait coimmunoprecipitation anti bait coip western blot western blot Immuno blot Immuno blot Jones R., Ruas M., Gregory F., Moulin S., Delia D., Manoukian S., Rowe J., Brookes S., Peters G. Apoptosis - Interactions involving proteins with a function related to apoptosis There are two experiments which are similar with Milan HDFs; because of different treatments I have created separate experiments with different exp-modification annotation. To enhance expression of p14ARF, cells were infected with a recombinant retrovirus encoding an ER-E2F1 fusion protein. Upon addition of 4-hydroxy tamoxifen to activate E2F1 expression, p14ARF became detectable by immunoblotting. gordon.peters@cancer.org.uk Accepted 2007-Not a month!-13 by DAVET. 22-Jan-2008: Contacted by JYOTI. Cancer Res. (0008-5472) 2007 davet IMEx A CDKN2A mutation in familial melanoma that abrogates binding of p16INK4a to CDK4 but not CDK6. A CDKN2A mutation in familial melanoma that abrogates binding of p16INK4a to CDK4 but not CDK6. Cancer Res. (0008-5472) 2007 imex curation Jones R., Ruas M., Gregory F., Moulin S., Delia D., Manoukian S., Rowe J., Brookes S., Peters G. Apoptosis - Interactions involving proteins with a function related to apoptosis Cancer - Interactions investigated in the context of cancer There are two experiments which are similar with Milan HDFs; because of different treatments I have created separate experiments with different exp-modification annotation. To enhance expression of p14ARF, cells were infected with a recombinant retrovirus encoding an ER-E2F1 fusion protein. Upon addition of 4-hydroxy tamoxifen to activate E2F1 expression, p14ARF became detectable by immunoblotting. gordon.peters@cancer.org.uk 22-Jan-2008: Contacted by JYOTI. davet Only protein-protein interactions imex curation human-hs68 Homo sapiens Hs68 normal diploid foreskin fibroblasts hs68 Human Hs68 normal diploid foreskin fibroblasts anti bait coip anti bait coimmunoprecipitation anti bait coip anti tag western anti tag western blot anti tag western Jones R., Ruas M., Gregory F., Moulin S., Delia D., Manoukian S., Rowe J., Brookes S., Peters G. Apoptosis - Interactions involving proteins with a function related to apoptosis There are two experiments which are similar with Milan HDFs; because of different treatments I have created separate experiments with different exp-modification annotation. To enhance expression of p14ARF, cells were infected with a recombinant retrovirus encoding an ER-E2F1 fusion protein. Upon addition of 4-hydroxy tamoxifen to activate E2F1 expression, p14ARF became detectable by immunoblotting. gordon.peters@cancer.org.uk Accepted 2007-Not a month!-13 by DAVET. 22-Jan-2008: Contacted by JYOTI. Cancer Res. (0008-5472) 2007 davet IMEx cdn2a_human Cyclin-dependent kinase inhibitor 2A CDKN2A CDKN2 Cyclin-dependent kinase 4 inhibitor A p16-INK4a Multiple tumor suppressor 1 MTS1 protein protein human Homo sapiens Human MEPAAGSSMEPSADWLATAAARGRVEEVRALLEAGALPNAPNSYGRRPIQVMMMGSARVAELLLLHGAEPNCADPATLTRPVHDAAREGFLDTLVVLHRAGARLDVRDAWGRLPVDLAEELGHRDVARYLRAAAGGTRGSNHARIDAAEGPSDIPD E59C0E6174B48255 cdk6_human Cyclin-dependent kinase 6 CDK6 Serine/threonine-protein kinase PLSTIRE Cell division protein kinase 6 CDKN6 protein protein human Homo sapiens Human MEKDGLCRADQQYECVAEIGEGAYGKVFKARDLKNGGRFVALKRVRVQTGEEGMPLSTIREVAVLRHLETFEHPNVVRLFDVCTVSRTDRETKLTLVFEHVDQDLTTYLDKVPEPGVPTETIKDMMFQLLRGLDFLHSHRVVHRDLKPQNILVTSSGQIKLADFGLARIYSFQMALTSVVVTLWYRAPEVLLQSSYATPVDLWSVGCIFAEMFRRKPLFRGSSDVDQLGKILDVIGLPGEEDWPRDVALPRQAFHSKSAQPIEKFVTDIDELGKDLLLKCLTFNPAKRISAYSALSHPYFQDLERCKENLDSHLPPSQNTSELNTA 571733EE6BE7FD4A arf_human Tumor suppressor ARF p14ARF CDKN2A CDKN2 MLM Alternative reading frame Cyclin-dependent kinase inhibitor 2A protein protein human Homo sapiens Human MVRRFLVTLRIRRACGPPRVRVFVVHIPRLTGEWAAPGAPAAVALVLMLLRSQRLGQQPLPRRPGHDDGQRPSGGAAAAPRRGAQLRRPRHSHPTRARRCPGGLPGHAGGAAPGRGAAGRARCLGPSARGPG DIP protein Q8N726 original sequence version: 97 DIP protein Q8N726 original sequence version: 113 DIP protein Q8N726 original sequence version: 72 7739A9050C21BC96 cdk4_human Cyclin-dependent kinase 4 CDK4 Cell division protein kinase 4 PSK-J3 protein protein human Homo sapiens Human MATSRYEPVAEIGVGAYGTVYKARDPHSGHFVALKSVRVPNGGGGGGGLPISTVREVALLRRLEAFEHPNVVRLMDVCATSRTDREIKVTLVFEHVDQDLRTYLDKAPPPGLPAETIKDLMRQFLRGLDFLHANCIVHRDLKPENILVTSGGTVKLADFGLARIYSYQMALTPVVVTLWYRAPEVLLQSTYATPVDMWSVGCIFAEMFRRKPLFCGNSEADQLGKIFDLIGLPPEDDWPRDVSLPRGAFPPRGPRPVQSVVPEMEESGAQLLLEMLTFNPHKRISAFRALQHSYLHKDEGNPE DIP protein P11802 original sequence version: 177 DIP protein P11802 original sequence version: 135 DIP protein P11802 original sequence version: 136 DIP protein P11802 original sequence version: 200 DIP protein P11802 original sequence version: 86 0916A0C07403A33A mdm2_human E3 ubiquitin-protein ligase Mdm2 MDM2 p53-binding protein Mdm2 Oncoprotein Mdm2 Double minute 2 protein RING-type E3 ubiquitin transferase Mdm2 protein protein human Homo sapiens Human MCNTNMSVPTDGAVTTSQIPASEQETLVRPKPLLLKLLKSVGAQKDTYTMKEVLFYLGQYIMTKRLYDEKQQHIVYCSNDLLGDLFGVPSFSVKEHRKIYTMIYRNLVVVNQQESSDSGTSVSENRCHLEGGSDQKDLVQELQEEKPSSSHLVSRPSTSSRRRAISETEENSDELSGERQRKRHKSDSISLSFDESLALCVIREICCERSSSSESTGTPSNPDLDAGVSEHSGDWLDQDSVSDQFSVEFEVESLDSEDYSLSEEGQELSDEDDEVYQVTVYQAGESDTDSFEEDPEISLADYWKCTSCNEMNPPLPSHCNRCWALRENWLPEDKGKDKGEISEKAKLENSTQAEEGFDVPDCKKTIVNDSRESCVEENDDKITQASQSQESEDYSQPSTSSSIIYSSQEDVKEFEREETQDKEESVESSLPLNAIEPCVICQGRPKNGCIVHGKTGHLMACFTCAKKLKKRNKPCPVCRQPIQMIVLTYFP DIP protein Q00987 original sequence version: 93 DIP protein Q00987-1 original sequence version: 192 DIP protein Q00987 original sequence version: 88 DIP protein Q00987 original sequence version: 180 DIP protein Q00987 original sequence version: 188 DIP protein Q00987 original sequence version: 189 DIP protein Q00987 original sequence version: 115 DIP protein Q00987-1 original sequence version: null DIP protein Q00987 original sequence version: 149 DIP protein Q00987 original sequence version: 146 DIP protein Q00987 original sequence version: 140 DIP protein Q00987 original sequence version: 183 DIP protein Q00987 original sequence version: 145 DIP protein Q00987 original sequence version: 182 DIP protein Q00987 original sequence version: 151 DIP protein Q00987 original sequence version: 156 DIP protein Q00987-1 original sequence version: 160 DIP protein Q00987 original sequence version: 160 DIP protein Q00987 original sequence version: 168 DIP protein Q00987 original sequence version: 186 DIP protein Q00987 original sequence version: 206 F37CE163876BC983 cdk4-cdkn2a-4 2 6 unspecified role unspecified role prey prey P42771:p.Arg24Pro mutation disrupting mutation disrupting interaction mutation disrupting mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain R P Wed May 02 19:06:11 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'arg24pro' Tue Jun 30 18:16:45 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg24Pro' P42771:p.Ala20Pro mutation disrupting mutation disrupting interaction mutation disrupting mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain A P Wed May 02 16:24:49 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'ala20pro' Tue Jun 30 16:33:39 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ala20Pro' region ha tag ha tag YPYDVPDYA epitope tag YPYDVPDYA epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 9 unspecified role unspecified role bait bait physical association physical association 1 B 2HA-tagged wild-type p16INK4a coprecipitated with both CDK4 and CDK6, whereas the A20P variant did not. In line with the in vitro binding data, the R24P variant coprecipitated with CDK6 but not with CDK4. P42771 infection The arg24pro mutation in p16INK4A does not affect binding to CDK6, although it abrogates binding to CDK4. cdk4-cdkn2a-3 3 6 unspecified role unspecified role prey prey region 35s radiolabel 35s radiolabel 35S s35 radiolabelled S35 s35 radiolabelled 35S S35 undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined P42771:p.Ala20Pro mutation disrupting strength mutation disrupting interaction strength mutation disrupting strength certain certain sequence position certain certain certain sequence position certain A P Wed May 02 14:44:44 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'ala20pro' Tue Jun 30 20:06:51 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ala20Pro' undefined mutation mutation disrupting strength mutation disrupting interaction strength mutation disrupting strength certain certain sequence position certain certain certain sequence position certain Wed Jul 06 16:30:11 BST 2016 Sequence change details about this feature cannot be ascertained or do not fit with the current version of the referenced protein, so they have been deleted as a result of our quality control procedures. The original label was 'arg24pro' in vitro In vitro 9 unspecified role unspecified role bait bait region 35s radiolabel 35s radiolabel 35S s35 radiolabelled S35 s35 radiolabelled 35S S35 undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined in vitro In vitro physical association physical association 1 A cdk6-cdkn2a-2 2 6 unspecified role unspecified role prey prey region ha tag ha tag YPYDVPDYA epitope tag YPYDVPDYA epitope tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined P42771:p.Ala20Pro mutation disrupting mutation disrupting interaction mutation disrupting mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain A P Wed May 02 18:51:33 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'ala20pro' Tue Jun 30 20:12:18 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ala20Pro' 7 unspecified role unspecified role bait bait physical association physical association 1 B 2HA-tagged wild-type p16INK4a coprecipitated with both CDK4 and CDK6, whereas the A20P variant did not. In line with the in vitro binding data, the R24P variant coprecipitated with CDK6 but not with CDK4. The arg24pro mutation in p16INK4A does not affect binding to CDK6, although it abrogates binding to CDK4. P42771 infection cdk6-cdkn2a-3 3 7 unspecified role unspecified role bait bait region 35s radiolabel 35s radiolabel 35S s35 radiolabelled S35 s35 radiolabelled 35S S35 undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined 6 unspecified role unspecified role prey prey P42771:p.Ala20Pro mutation disrupting mutation disrupting interaction mutation disrupting mutation analysis mutation analysis certain certain sequence position certain certain certain sequence position certain A P Thu Jul 07 12:16:15 BST 2016 This feature has been corrected as a result of our quality control procedures. The original label was ala20pro Wed May 02 15:44:50 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'ala20pro' Tue Jun 30 20:12:40 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Ala20Pro' region 35s radiolabel 35s radiolabel 35S s35 radiolabelled S35 s35 radiolabelled 35S S35 undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined physical association physical association 1 A cdkn2a-cdk6-2 1 6 unspecified role unspecified role prey prey arg24pro variant variant certain certain sequence position certain certain certain sequence position certain 7 unspecified role unspecified role bait bait physical association physical association 2 B the 16INK4a immune complexes from Milan cells contained CDK6 but not CDK4 In Milan HDF lysates p16INK4A R24P coimmunoprecipitates CDK6 but not CDK4. cdk6-cdkn2a-5 1 6 unspecified role unspecified role bait bait arg24pro variant variant certain certain sequence position certain certain certain sequence position certain R P 7 unspecified role unspecified role prey prey physical association physical association 2 B In Milan HDF lysates p16INK4A R24P coimmunoprecipitates with CDK6 but not CDK4. p16ink4a-cdk4-1 5 6 unspecified role unspecified role bait bait 7 unspecified role unspecified role prey prey 9 unspecified role unspecified role prey prey association association 2 B In the normal HDFs, both CDK4 and CDK6 were present in the p16INK4a immunoprecipitates cdk6-cdkn2a-4 5 6 unspecified role unspecified role prey prey 7 unspecified role unspecified role bait bait physical association physical association 2 B In the normal HDFs, both CDK4 and CDK6 were present in the p16INK4a immunoprecipitates and endogenous p16INK4a was coprecipitated with CDK4 and CDK6 cdk4-cdkn2a-5 5 9 unspecified role unspecified role bait bait 6 unspecified role unspecified role prey prey physical association physical association 2 B In the normal HDFs, both CDK4 and CDK6 were present in the p16INK4a immunoprecipitates and endogenous p16INK4a was coprecipitated with CDK4 and CDK6 p16INK4A (R24P) does not coimmunoprecipitate with CDK4 in Milan HDF lysates. arf-mdm2-1 4 8 unspecified role unspecified role bait bait 10 unspecified role unspecified role prey prey physical association physical association 2 C Induction of ARF was accompanied by a corresponding up-regulation of MDM2 and p53, and under these conditions it was possible to show an association between endogenous ARF and MDM2