Proteins / BRAF
BRAF
Serine/threonine-protein kinase B-raf
RAF kinase
UniProt P15056
HSP90 client (literature): weak
3D structure ↓
19 interaction partners · volcano ↗
MAPK pathway activity (phosphorylated ERK2 reporter) under basal conditions. Scores are WT-relative: 1 = wild type.
16,218 variantsmissense decreased 19% · increased 24%3,308 dominant negative variants
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.
Fraction dominant-negative
0%25%50%75%100%
Fraction of variants at this position called dominant negative: basal pathway activity below the empty-vector threshold (basal activity only).
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 | |
|---|---|---|---|---|---|---|---|---|
| KSR2 STKc_Raf | RF2-PPI | -0.43 | 2.9e-68 | +0.81 | 5.7e-22 | 12 | supported | Structure ↗ |
| BRAF STKc_Raf | PDB | -0.38 | 1.0e-50 | +0.78 | 2.7e-17 | 11 | supported | Structure ↗ |
| ARAF | AF-M | -0.43 | 2.1e-49 | +0.82 | 9.3e-20 | 11 | supported | Structure ↗ |
| KSR2 | AF-M | -0.40 | 4.1e-48 | +0.51 | 4.6e-11 | 20 | supported | Structure ↗ |
| CRAF | AF-M | -0.43 | 2.1e-42 | +0.82 | 7.2e-17 | 10 | supported | Structure ↗ |
| ITCH | AF-M | +1.01 | 2.5e-39 | -0.57 | 7.0e-10 | 9 | supported | Structure ↗ |
| KSR1 | AF-M | -0.38 | 2.4e-37 | +0.48 | 3.7e-09 | 21 | supported | Structure ↗ |
| CDC37 | PDB | -0.25 | 3.1e-37 | -0.61 | 2.9e-06 | 11 | supported | Structure ↗ |
| KSR1 | RF2-PPI | -0.36 | 1.6e-36 | +0.45 | 3.7e-09 | 21 | supported | Structure ↗ |
| YWHAZ res 241-719 | PDB | +1.12 | 2.7e-29 | -0.61 | 8.1e-16 | 10 | supported | Structure ↗ |
| MEK2 | RF2-PPI | +0.26 | 4.4e-26 | +0.03 | 0.609 | 9 | supported | Structure ↗ |
| MAP2K3 | AF-M | -0.04 | 3.5e-25 | +0.18 | 0.019 | 9 | supported | Structure ↗ |
| MAP2K6 | AF-M | -0.05 | 7.2e-24 | +0.21 | 0.009 | 8 | supported | Structure ↗ |
| MEK1 | PDB | +0.06 | 9.4e-23 | +0.06 | 0.033 | 17 | supported | Structure ↗ |
| STK11 | AF-M | -0.11 | 3.9e-21 | +0.23 | 0.002 | 11 | supported | Structure ↗ |
| STK11 | RF2-PPI | -0.13 | 3.9e-16 | +0.24 | 0.002 | 10 | supported | Structure ↗ |
| V9P4T4 | PDB | +1.11 | 1.4e-13 | -0.60 | 5.9e-13 | 11 | supported | Structure ↗ |
| RAP1A | AF-M | -0.23 | 6.9e-05 | +0.35 | 1.9e-04 | 8 | supported | Structure ↗ |
| KRAS | PDB | -0.29 | 1.9e-04 | +0.35 | 9.7e-04 | 6 | supported | Structure ↗ |
| BRAF STKc_Raf #2 | PDB | +0.48 | 0.009 | -0.22 | 2.3e-04 | 15 | supported | Structure ↗ |
| RAP1B | AF-M | -0.21 | 0.002 | +0.32 | 0.001 | 7 | supported | Structure ↗ |
| MRAS | AF-M | -0.21 | 0.009 | +0.31 | 0.002 | 10 | supported | Structure ↗ |
| KSR2 res 49-77 | RF2-PPI | -0.28 | 0.033 | -0.02 | 0.534 | 10 | supported | Structure ↗ |
| HRAS | AF-M | +0.49 | 0.046 | -0.15 | 0.167 | 11 | supported | Structure ↗ |
| MEK1 | RF2-PPI | -0.04 | 1.9e-25 | +0.10 | 0.182 | 10 | not supported | Structure ↗ |
| MEK2 | AF-M | -0.09 | 6.9e-20 | +0.12 | 0.069 | 12 | not supported | Structure ↗ |
| MEK1 | AF-M | -0.07 | 9.7e-19 | +0.13 | 0.061 | 10 | not supported | Structure ↗ |
| A0A1B0GUL7 | RF2-PPI | -0.08 | 5.6e-16 | +0.12 | 0.158 | 8 | not supported | Structure ↗ |
| MAP2K7 | AF-M | -0.04 | 6.7e-15 | +0.15 | 0.116 | 5 | not supported | Structure ↗ |
| BRAF STKc_Raf #3 | PDB | -0.15 | 0.002 | -0.01 | 0.795 | 13 | not supported | Structure ↗ |
| YWHAZ res 239-735 | PDB | -0.07 | 0.045 | +0.09 | 0.388 | 7 | not supported | Structure ↗ |
| NRAS | AF-M | +0.42 | 0.127 | -0.14 | 0.883 | 13 | not supported | Structure ↗ |
| HSP90AB1 | PDB | +0.23 | 0.834 | -0.05 | 0.215 | 4 | not supported | Structure ↗ |
| KRAS | AF-M | +0.32 | 0.295 | -0.07 | 0.445 | 12 | not supported | Structure ↗ |
| YWHAZ STKc_Raf | PDB | -0.21 | 0.320 | -0.16 | 0.340 | 5 | not supported | Structure ↗ |