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Group by :Switch typeMotif classProteinEnzymePathway            Group Index    Colouring Info              Filtered: PFAM:PF02174 (14 hits) x
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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

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Type: Binary Subtype: Physicochemical compatibilityType: Binary Subtype: Pre‑translationalType: Specificity Subtype: Altered binding specificity
Type: Specificity Subtype: Competition


ProteinMotifStartEndSwitch descriptionInformation

Type: Specificity Subtype: Competition
Competitive binding of multiple binding partners to overlapping or adjacent, mutually exclusive interaction interfaces depends on local target protein abundance, which can be regulated by changing the expression level or subcellular localisation of the competitors, or by scaffolding.
ITB7_HUMANLIG_Talin770779The integrin regulator Talin-1 (TLN1) and the actin-crosslinking Filamins Filamin-A (FLNA) use overlapping binding sites on the cytoplasmic tails of beta integrin subunits Integrin beta-7 (ITGB7), which makes their interaction with beta integrin mutually exclusive.
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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_HUMANLIG_PTB_Phospho_111041110Phosphorylation of Y1110 in the PTB-binding motif of Epidermal growth factor receptor (EGFR) induces binding to the Docking protein 1 (DOK1) protein.
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IL4RA_HUMANLIG_PTB_Phospho_1491497Phosphorylation of Y497 in the PTB-binding motif of Interleukin-4 receptor subunit alpha (IL4R) induces binding to the Insulin receptor substrate 1 (IRS1) protein.
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ITB3_HUMANLIG_PTB_Phospho_1767773Phosphorylation of Y773 in the PTB-binding motif of Integrin beta-3 (ITGB3) induces binding to the Docking protein 1 (DOK1) protein.
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MUSK_MOUSELIG_PTB_Phospho_1547553Phosphorylation of Y553 in the PTB-binding motif of Muscle, skeletal receptor tyrosine-protein kinase (Musk) induces binding to the Protein Dok-7 (Dok7) protein.
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RET_MOUSELIG_PTB_Phospho_110571063Phosphorylation 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.
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PI51C_HUMANLIG_PTB_Talin650653Phosphorylation of S650 in the PTB-binding motif of Phosphatidylinositol-4-phosphate 5-kinase type-1 gamma (PIP5K1C) blocks its interaction with Talin-1 (TLN1). Phosphorylation of Y649 by Src kinase enhances the interaction, possibly indirectly by inhibiting S650 phosphorylation.
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PI51C_MOUSELIG_PTB_Talin645648Phosphorylation of S645 in the PTB-binding motif of Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c) by Cyclin-dependent kinase 5 (Cdk5) inhibits its interaction with Talin-1 (Tln1).
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PI51C_MOUSELIG_PTB_Talin645648Phosphorylation of Y644 in Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c) promotes its association with Talin-1 (Tln1).
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Type: Binary Subtype: Pre‑translational
Pre-translational mechanisms such as alternative splicing, alternative promoter-usage and/or RNA editing result in inclusion or removal of exons that contain an entire or partial motif.
ITB1_HUMANLIG_Talin775785Alternative splicing alters the flanking regions of the PTB-binding motif of Isoform Beta-1D of Integrin beta-1 (ITGB1), inducing higher affinity binding to Talin-1 (TLN1). Alteration of residue 788 from G to Q and alteration of residue 786 from A to P increases the binding affinity from 491 micromolar in the canonical Isoform Beta-1A of Integrin beta-1 (ITGB1) to 95 micromolar in Isoform Beta-1D of Integrin beta-1 (ITGB1).
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ITB1_HUMANLIG_Talin775785Alternative splicing alters the flanking regions of the PTB-binding motif of Isoform Beta-1D of Integrin beta-1 (ITGB1), inducing higher affinity binding to Talin-2 (TLN2). The alteration of residue 788 from G to Q and alteration of residue 786 from A to P increases the binding affinity from 652 micromolar in the canonical Isoform Beta-1A of Integrin beta-1 (ITGB1) to 36 micromolar in Isoform Beta-1D of Integrin beta-1 (ITGB1).
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PI51C_MOUSELIG_PTB_Talin645648Alternative splicing removes the PTB domain-binding motif of Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c), abrogating binding to Talin-1 (Tln1). Integrin receptors, Tln1 and Isoform PIPKIgamma661 of Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (Pip5k1c) (PIPKIgamma661) are recruited to focal adhesions, inducing synthesis of PI(4,5)P2. The regulated and localised generation of PI(4,5)P2 facilitates the assembly and/or disassembly of focal adhesions.
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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_HUMANLIG_PTB_Apo_2767774Phosphorylation 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.
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ITB3_HUMANLIG_PTB_Phospho_1767773Phosphorylation 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.
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