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| Domain hiding | Altered binding specificity | Motif hiding | Composite binding site formation |
| Uncategorised | Rheostatic | Allostery | Avidity-sensing |
| Physicochemical compatibility | Pre-translational | Competition |
| Motif | Start | End | Switch Type | Switch Subtype | Switch Description | Information |
Ataxin-1 - ATXN1 - Homo sapiens | |||||||
| LIG_14-3-3_1 | 772 | 777 | Binary | Physicochemical compatibility | Phosphorylation of S775 by RAC-alpha serine/threonine-protein kinase (AKT1) in the 14-3-3-binding motif of Ataxin-1 (ATXN1) induces binding to the 14-3-3 protein zeta/delta (YWHAZ) protein. | ||
Cyclin-dependent kinase inhibitor 1 - CDKN1A - Homo sapiens | |||||||
| LIG_PCNA_PIPBox_1 | 144 | 153 | Binary | Physicochemical compatibility | Phosphorylation of T145 in the PCNA-binding motif of Cyclin-dependent kinase inhibitor 1 (CDKN1A) by RAC-alpha serine/threonine-protein kinase (AKT1) inhibits binding to Proliferating cell nuclear antigen (PCNA). As a result, Cyclin-dependent kinase inhibitor 1 (CDKN1A) no longer inhibits Proliferating cell nuclear antigen (PCNA) and blocking of DNA replication is relieved. | ||
Cyclin-dependent kinase inhibitor 1B - CDKN1B - Homo sapiens | |||||||
| LIG_14-3-3_3 | 154 | 159 | Specificity | Motif hiding | Phosphorylation of a 14-3-3-binding motif in the NLS of Cyclin-dependent kinase inhibitor 1B (CDKN1B) by RAC-alpha serine/threonine-protein kinase (AKT1) induces binding of 14-3-3 protein gamma (YWHAG), which hides the NLS and prevents binding to Importin subunit alpha-1 (KPNA1), thereby mediating cytoplasmic retention of Cyclin-dependent kinase inhibitor 1B (CDKN1B). Binding of 14-3-3 dimer involves an additional C-terminal 14-3-3-binding motif (see switch details). | ||
| LIG_14-3-3_3 | 154 | 159 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Cyclin-dependent kinase inhibitor 1B (CDKN1B) by RAC-alpha serine/threonine-protein kinase (AKT1) and ribosomal protein S6 kinases (Ribosomal protein S6 kinase alpha-1 (RPS6KA1), Ribosomal protein S6 kinase alpha-3 (RPS6KA3)) induces binding of 14-3-3 dimer. Binding of 14-3-3 results in cytoplasmic localisation of Cyclin-dependent kinase inhibitor 1B (CDKN1B) (see switch details), thereby alleviating Cyclin-dependent kinase inhibitor 1B (CDKN1B)-mediated inhibition of cyclin-dependent kinases and cell cycle progression. | |||
| LIG_14-3-3_3 | 193 | 198 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Cyclin-dependent kinase inhibitor 1B (CDKN1B) by RAC-alpha serine/threonine-protein kinase (AKT1) and ribosomal protein S6 kinases (Ribosomal protein S6 kinase alpha-1 (RPS6KA1), Ribosomal protein S6 kinase alpha-3 (RPS6KA3)) induces binding of 14-3-3 dimer. Binding of 14-3-3 results in cytoplasmic localisation of Cyclin-dependent kinase inhibitor 1B (CDKN1B) (see switch details), thereby alleviating Cyclin-dependent kinase inhibitor 1B (CDKN1B)-mediated inhibition of cyclin-dependent kinases and cell cycle progression. | |||
Forkhead box protein O3 - FOXO3 - Homo sapiens | |||||||
| LIG_14-3-3_3 | 250 | 255 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Forkhead box protein O3 (FOXO3) by RAC-alpha serine/threonine-protein kinase (AKT1) induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (YWHAB). This interaction results in cytoplasmic retention and inactivation of Forkhead box protein O3 (FOXO3). | |||
| LIG_14-3-3_3 | 29 | 34 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Forkhead box protein O3 (FOXO3) by RAC-alpha serine/threonine-protein kinase (AKT1) induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (YWHAB). This interaction results in cytoplasmic retention and inactivation of Forkhead box protein O3 (FOXO3). | |||
Forkhead box protein O4 - FOXO4 - Homo sapiens | |||||||
| LIG_14-3-3_2 | 193 | 199 | Binary | Physicochemical compatibility | Phosphorylation of S197 by in the 14-3-3-binding motif of Forkhead box protein O4 (FOXO4) induces binding to the 14-3-3 protein zeta/delta (YWHAZ) protein. | ||
| LIG_14-3-3_1 | 29 | 34 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Foxo4 by PKB induces binding of 14-3-3 dimer. In the nucleus, this blocks binding to DNA, while in the cytoplasm it blocks reimport of Foxo4 into the nucleus by blocking its Nuclear Localisation Signal (NLS). Since binding of 14-3-3 to a single motif occurs with an affinity similar to the affinity of Foxo4 for DNA, multivalent binding of 14-3-3 dimer is required for efficient inhibition of DNA binding. | |||
| LIG_14-3-3_2 | 193 | 199 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Foxo4 by PKB induces binding of 14-3-3 dimer. In the nucleus, this blocks binding to DNA, while in the cytoplasm it blocks reimport of Foxo4 into the nucleus by blocking its Nuclear Localisation Signal (NLS). Since binding of 14-3-3 to a single motif occurs with an affinity similar to the affinity of Foxo4 for DNA, multivalent binding of 14-3-3 dimer is required for efficient inhibition of DNA binding. | |||
RAC-alpha serine/threonine-protein kinase - AKT1 - Homo sapiens | |||||||
| DOC_AGCK_PIF_1 | 469 | 474 | Binary | Physicochemical compatibility | Phosphorylation of S473 in the PIF motif of RAC-alpha serine/threonine-protein kinase (AKT1) by Serine/threonine-protein kinase mTOR (MTOR) (as part of mTORC2 complex) induces intramolecular interaction with the PIF-binding pocket, resulting in cis-activation of RAC-alpha serine/threonine-protein kinase (AKT1). Dephosphorylation of the PIF motif by PHLPP1/2 (PHLPP1 for Akt2/3 and PHLPP2 for Akt1/3) results in reduced Akt activity, probably by disrupting the interaction with the Akt PIF pocket and thus cis-activation. | ||
| DOC_WW_Pin1_4 | 447 | 452 | Binary | Physicochemical compatibility | Phosphorylation of T450 in the Pin1-binding motif of RAC-alpha serine/threonine-protein kinase (AKT1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
| DOC_WW_Pin1_4 | 89 | 94 | Binary | Physicochemical compatibility | Phosphorylation of T92 in the Pin1-binding motif of RAC-alpha serine/threonine-protein kinase (AKT1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein. | ||
RAF proto-oncogene serine/threonine-protein kinase - RAF1 - Homo sapiens | |||||||
| LIG_14-3-3_1 | 256 | 261 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in RAF proto-oncogene serine/threonine-protein kinase (RAF1) in response to growth factors induces high-avidity binding to dimeric 14-3-3 protein zeta/delta (YWHAZ), with pS621 being the high-affinity interaction site. This interaction locks RAF proto-oncogene serine/threonine-protein kinase (RAF1) in an inhibited conformation. | |||