Domain hiding |   Altered binding specificity |   Motif hiding |   Composite binding site formation |
  Uncategorised |   Rheostatic |   Allostery |   Avidity-sensing |
  Physicochemical compatibility |   Pre-translational |   Competition |
Type: Binary Subtype: Pre‑translational | Type: Specificity Subtype: Altered binding specificity |
Protein | Motif | Start | End | Switch description | Information |
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. | |||||||
B2L11_HUMAN | DEG_SCF_TRCP1_2 | 93 | 98 | Alternative splicing removes the extended SCF-TrCP degron motif of Bcl-2-like protein 11 (BCL2L11), abrogating binding to F-box/WD repeat-containing protein 1A (BTRC). Upon mitogen survival signals, RPS6KA1 and RPS6KA2 kinases are up-regulated and rapidly phosphorylate the three serines of Isoform Bim(EL) of Bcl-2-like protein 11 (BCL2L11). This facilitates the binding of betaTrCP and subsequent ubiquitination and degradation of Isoform Bim(EL) of Bcl-2-like protein 11 (BCL2L11). | |||
REST_HUMAN | DEG_SCF_TRCP1_2 | 1008 | 1013 | Alternative splicing removes the beta-TrCP-binding degron of RE1-silencing transcription factor (REST), abrogating binding to F-box/WD repeat-containing protein 1A (BTRC), and therefore altering the half-life of the variant. Up-regulation of the protein isoform without the degron has been linked to cancer. | |||
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. | |||||||
YAP1_HUMAN | DEG_SCF_TRCP1_2 | 383 | 387 | Phosphorylation of Yorkie homolog (YAP1) at S381 by Serine/threonine-protein kinase LATS1 (LATS1) (a key regulator of the Hippo Pathway) primes the sequence for phosphorylation by Casein kinase I isoform epsilon (CSNK1E) at S384 and S387. This targets YAP1 to the SCF ubiqutin ligase complex, F-box/WD repeat-containing protein 1A (BTRC), which marks is YAP1 for subsequent degradation by the proteasomal system. N.B. Serine/threonine-protein kinase LATS2 (LATS2) can replace LATS1 and Casein kinase I isoform delta (CSNK1D) can replace CSNK1E |