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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 |
| Type: Binary Subtype: Physicochemical compatibility | Type: Cumulative Subtype: Rheostatic | Type: Specificity Subtype: Altered binding specificity |
| Protein | Motif | Start | End | Switch description | Information |
Type: Binary Subtype: Physicochemical compatibility | |||||||
| PTM of a residue in a motif or in its flanking regions alters the physicochemical and/or structural compatibility of the motif with its binding partner. This can either induce or enhance an interaction, or result in inhibition or even abrogation of an interaction. | |||||||
| EGFR_HUMAN | LIG_PTB_Phospho_1 | 1104 | 1110 | Phosphorylation of Y1110 in the PTB-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the Docking protein 1 (DOK1) protein. | |||
| ERBB3_HUMAN | LIG_PTB_Phospho_1 | 1322 | 1328 | Phosphorylation of Y1328 in the PTB-binding motif of Receptor tyrosine-protein kinase erbB-3 (ERBB3) induces binding to the SHC-transforming protein 1 (SHC1) protein. | |||
| IL2RB_HUMAN | LIG_PTB_Phospho_1 | 358 | 364 | Phosphorylation of Y364 in the PTB-binding motif of Interleukin-2 receptor subunit beta (IL2RB) induces binding to the SHC-transforming protein 1 (SHC1) protein. | |||
| IL4RA_HUMAN | LIG_PTB_Phospho_1 | 491 | 497 | Phosphorylation of Y497 in the PTB-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the Insulin receptor substrate 1 (IRS1) protein. | |||
| INSR_HUMAN | LIG_PTB_Phospho_1 | 993 | 999 | Phosphorylation of Y999 in the PTB-binding motif of Insulin receptor (INSR) induces binding to the SHC-transforming protein 1 (SHC1) protein. | |||
| ITB3_HUMAN | LIG_PTB_Phospho_1 | 767 | 773 | Phosphorylation of Y773 in the PTB-binding motif of Integrin beta-3 (ITGB3) induces binding to the Docking protein 1 (DOK1) protein. | |||
| ITB3_HUMAN | LIG_PTB_Phospho_1 | 779 | 785 | Phosphorylation of Y785 in the PTB-binding motif of Integrin beta-3 (ITGB3) induces binding to the SHC-transforming protein 1 (SHC1) protein. | |||
| ITB4_HUMAN | LIG_PTB_Phospho_1 | 1590 | 1596 | Phosphorylation of Y1596 in the PTB-binding motif of Integrin beta-4 (ITGB4) induces binding to the SHC-transforming protein 1 (SHC1) protein. | |||
| LRP1_HUMAN | LIG_PTB_Phospho_1 | 4501 | 4507 | Phosphorylation of Y4507 in the PTB-binding motif of Prolow-density lipoprotein receptor-related protein 1 (LRP1) induces binding to the SHC-transforming protein 1 (SHC1) protein. | |||
| MT_POVMA | LIG_PTB_Phospho_1 | 244 | 250 | Phosphorylation of Y250 in the PTB-binding motif of Middle T antigen induces binding to the SHC-transforming protein 1 (Shc1) protein. | |||
| MUSK_MOUSE | LIG_PTB_Phospho_1 | 547 | 553 | Phosphorylation of Y553 in the PTB-binding motif of Muscle, skeletal receptor tyrosine-protein kinase (Musk) induces binding to the Protein Dok-7 (Dok7) protein. | |||
| NTRK1_HUMAN | LIG_PTB_Phospho_1 | 490 | 496 | Phosphorylation of Y496 in the PTB-binding motif of High affinity nerve growth factor receptor (NTRK1) induces binding to the SHC-transforming protein 1 (SHC1) protein. | |||
| RET_MOUSE | LIG_PTB_Phospho_1 | 1057 | 1063 | Phosphorylation of Y1063 in the PTB-binding motif of Proto-oncogene tyrosine-protein kinase receptor Ret (Ret) induces binding to the Docking protein 1 (Dok1) protein. | |||
| SHIP1_HUMAN | LIG_PTB_Phospho_1 | 1016 | 1022 | Phosphorylation of Y1022 in the PTB-binding motif of Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 (INPP5D) induces binding to the SHC-transforming protein 1 (SHC1) protein. | |||
| SHIP1_HUMAN | LIG_PTB_Phospho_1 | 909 | 915 | Phosphorylation of Y915 in the PTB-binding motif of Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 (INPP5D) induces binding to the SHC-transforming protein 1 (SHC1) protein. | |||
| ITB3_HUMAN | LIG_PTB_Phospho_1 | 779 | 785 | Phosphorylation of T779 in the PTB-binding motif of Integrin beta-3 (ITGB3) inhibits its interaction with SHC-transforming protein 1 (SHC1). | |||
Type: Cumulative Subtype: Rheostatic | |||||||
| Rheostatic switches gradually alter the affinity of a motif for a single binding partner by addition of multiple PTMs that additively contribute to this modulation. Additional modifications can either strengthen or weaken an interaction. | |||||||
| ITB3_HUMAN | LIG_PTB_Phospho_1 | 779 | 785 | While phosphorylation of Y785 in the PTB-binding motif of Integrin beta-3 (ITGB3) induces binding to SHC-transforming protein 1 (SHC1), additional phosphorylation of Y773 further increases the strength of the interaction. | |||
Type: Specificity Subtype: Altered binding specificity | |||||||
| The balance of the competition for overlapping or adjacent, mutually exclusive interaction interfaces is tipped in favor of one of the interactors by PTM-dependent modulation of the intrinsic affinity of a binding region. Multiple, successive PTMs allow sequential switching of different binding partners in an ordered manner by step-wise alteration of binding specificity. | |||||||
| ITB3_HUMAN | LIG_PTB_Phospho_1 | 767 | 773 | Phosphorylation of Y773 in Integrin beta-3 (ITGB3) switches the specificity of ITGB3 from Talin-1 (TLN1) to Docking protein 1 (DOK1), with a 2-fold decrease of the affinity for TLN1 and close to a 400-fold increase of the affinity for DOK1. This switch results in negative regulation of integrin activation. | |||
| ITB3_HUMAN | LIG_PTB_Phospho_1 | 779 | 785 | Phosphorylation of Integrin beta-3 (ITGB3) at Y785 switches the specificity of integrin from Kindlin-2 (Fermitin family homolog 2 (FERMT2)) to the adaptor protein SHC-transforming protein 1 (SHC1). | |||