Skip to main content
. 2022 Jan 19;18(1):e10584. doi: 10.15252/msb.202110584

Figure 6. The amino acid resolution binding site information allows accurate predictions of functional effects of disease mutations and PTMs.

Figure 6

  1. PPI networks of KEAP1 showing reproducibly selected high/medium confidence interactions with mutations or phosphosites overlapping with the binding motif or in the flanking regions (± 2 residues).The disease‐associated mutation is colored in red (orange if not disease associated). Phosphosites are colored in gray. Dashed‐edges represent mutations or phosphosites in motif residues.
  2. FP competition experiments of wild‐type and disease mutant peptides binding to KEAP1 Kelch using FITC‐NFE2L1228–243 as probe (n = 3, technical replicates, shown are individual data points. Source data are provided).
  3. Peptide sequences related to the interactions shown in panel (A).
  4. PPI networks of KPNA4 showing reproducibly selected high/medium confidence interactions with mutations or phosphosites overlapping with the binding motif or in the flanking regions (± 2 residues).
  5. FP competition experiments of wild‐type, disease mutant, and phospho‐peptides binding to KPNA4. The affinities of NXK2‐5 wild‐type and K194R mutant for KPNA4 were determined using FITC‐Myc320–328 as a probe; the affinities of unphosphorylated and phosphorylated NCOR2 peptides were determined using FITC‐NCOR21307–1322 as probe (n = 3, technical replicates, shown are individual data points. Source data is provided).
  6. Peptide sequences related to the interactions shown in panel (D).
  7. Representative cellular localization experiments of the GFP‐based NLS sensor fused to wild‐type or K194R mutant NKX2‐5192–207 peptide. HEK293 cells were transiently transfected with the NLS sensor and fixed 36 h after transfection, and imaged using epifluorescence microscopy. The nucleus was stained with DAPI. The scale bar indicates 10 μm (n = 3, independent experiments).
  8. Peptides for additional baits with disease‐associated mutations in the consensus binding motif.

Data information: For (C), (F) and (H): Motifs are highlighted with blue background and key residues are indicated in bold letters, phosphosites are indicated by a box, and disease‐associated mutations of SLiMs are indicated in red bold letters.

Source data are available online for this figure.