Proteins / KSR2
KSR2
Kinase suppressor of Ras 2
Scaffold pseudokinase
UniProt Q6VAB6
HSP90 client (literature): strong
3D structure ↓
9 interaction partners · volcano ↗
Protein abundance under basal conditions (untreated, or vehicle where a drug arm exists). Scores are WT-relative: 1 = wild type.
10,300 variantsmissense decreased 16% · increased 1%
Other cells fade; highlighted cells are outlined.
Annotation tracks
Structure
Function
Chaperone
Variant effect
Track legend & definitions
Secondary structure
alpha helix3-10 helixpi helixbeta strandbeta bridgeturnbendno_ss
DSSP assignment on the reference structure.
Relative SASA
0.000.250.500.751.00
Side-chain solvent accessibility (0 = buried, 1 = fully exposed). The pipeline calls a residue surface-exposed above 0.25.
pLDDT
50.062.575.087.5100.0
AlphaFold per-residue confidence. The analysis drops residues below 60.
Curated feature
Protein-protein interfaceCatalytic / active siteLigand / substrate pocketRegulatory elementOther annotation
UniProt / literature annotation, coloured by class. Red marks a curated protein-protein interface — the independent comparison for our predicted interfaces.
Annotated interface
yesno
Curated protein-interface residue, independent of any structure prediction in this study.
Active site
yesno
Curated catalytic / active-site residue.
Inter-domain contact
yesno
Residue contacting another domain of the same protein (all-atom), so a variant effect there may be intramolecular rather than at a PPI.
HSP90 contact
TrueFalseUnknown
Contacts HSP90 in the chaperone-client cryo-EM structures ('Unknown' where the protein was not mapped).
CDC37 contact
TrueFalseUnknown
Contacts CDC37. These positions report kinase foldability rather than a canonical binding surface.
Fraction decreased
0%25%50%75%100%
Fraction of variants at this position classified decreased in this assay (2.5th-percentile rule).
Fraction increased
0%25%50%75%100%
Fraction of variants at this position classified increased in this assay.
Click a position for its interactions and annotations
— ■ the Interface strip marks
positions in ≥1 supported interface (darker = more partners)
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One row per interface: complexes of the same pair and source whose interfaces overlap (IoU ≥ 0.3) are merged, as in the Fig. 6c,d volcano plots (median Cohen's d; q from the geometric-mean p). Supported: at least one complex with q < 0.05 and |d| ≥ 0.2 in either basal assay.
| Partner | Source | Activity d | q | Abundance d | q | Interface positions | Supported | |
|---|---|---|---|---|---|---|---|---|
| MEK1 | AF-M | +0.92 | 8.5e-51 | -0.84 | 1.1e-38 | 16 | supported | Structure ↗ |
| MEK2 | AF-M | +0.92 | 3.7e-49 | -0.84 | 6.2e-38 | 17 | supported | Structure ↗ |
| KSR1 | AF-M | -0.69 | 1.2e-36 | +0.61 | 1.8e-12 | 18 | supported | Structure ↗ |
| MEK1 | PDB | +0.53 | 1.8e-21 | -0.74 | 2.1e-35 | 18 | supported | Structure ↗ |
| BRAF | AF-M | -0.66 | 5.2e-33 | +0.58 | 1.6e-10 | 20 | supported | Structure ↗ |
| PRKAA1 res 22-687 | AF-M | -0.66 | 2.5e-26 | +1.12 | 4.6e-10 | 15 | supported | Structure ↗ |
| SOX2 | AF-M | -1.00 | 2.2e-24 | +0.83 | 1.4e-12 | 5 | supported | Structure ↗ |
| FBXL2 | RF2-PPI | -1.02 | 2.8e-23 | +0.22 | 0.051 | 4 | supported | Structure ↗ |
| BRAF | RF2-PPI | -0.72 | 8.1e-23 | +0.59 | 1.1e-12 | 11 | supported | Structure ↗ |
| ARAF | AF-M | -0.63 | 8.2e-22 | +0.57 | 4.1e-11 | 14 | supported | Structure ↗ |
| CRAF | AF-M | -0.62 | 4.9e-19 | +0.55 | 4.0e-10 | 11 | supported | Structure ↗ |
| BRAF SAM_KSR1_N | RF2-PPI | -0.37 | 1.7e-06 | – | – | 10 | supported | Structure ↗ |
| PRKAA1 res 469-776 | AF-M | -0.44 | 9.8e-05 | +0.13 | 0.774 | 7 | supported | Structure ↗ |
| CDC27 | RF2-PPI | -0.03 | 0.782 | – | – | 5 | not supported | Structure ↗ |