Proteins / CRAF
CRAF
RAF proto-oncogene serine/threonine-protein kinase · gene RAF1
RAF kinase
UniProt P04049
HSP90 client (literature): strong
3D structure ↓
35 interaction partners · volcano ↗
MAPK pathway activity (phosphorylated ERK2 reporter) under basal conditions. Scores are WT-relative: 1 = wild type.
14,033 variantsmissense decreased 36% · increased 24%526 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 | AF-M | -1.21 | 5.9e-62 | +0.01 | 0.411 | 12 | supported | Structure ↗ |
| CLEC16A | AF-M | -1.44 | 4.2e-54 | -0.12 | 0.005 | 8 | supported | Structure ↗ |
| RAP1B | AF-M | -0.91 | 1.1e-43 | +0.33 | 1.3e-04 | 13 | supported | Structure ↗ |
| KSR1 | AF-M | -0.81 | 3.9e-43 | +0.06 | 0.171 | 13 | supported | Structure ↗ |
| ARAF | AF-M | -0.94 | 1.3e-39 | +0.04 | 0.342 | 14 | supported | Structure ↗ |
| CDC37 | PDB | -1.00 | 1.0e-33 | -1.07 | 1.8e-34 | 12 | supported | Structure ↗ |
| BRAF | AF-M | -0.95 | 1.3e-33 | -0.26 | 5.1e-04 | 11 | supported | Structure ↗ |
| STK3 STKc_C-Raf #2 | AF-M | -2.04 | 6.6e-32 | +0.11 | 0.963 | 3 | supported | Structure ↗ |
| GNB1 | RF2-PPI | -0.75 | 5.1e-28 | +0.20 | 0.003 | 11 | supported | Structure ↗ |
| RAP1A | PDB | -1.21 | 1.8e-26 | +0.11 | 0.252 | 7 | supported | Structure ↗ |
| GNB2 | AF-M | -1.06 | 7.5e-25 | -0.16 | 0.016 | 6 | supported | Structure ↗ |
| KRAS | PDB | -1.16 | 1.1e-24 | +0.09 | 0.138 | 7 | supported | Structure ↗ |
| NRAS | AF-M | -0.54 | 8.5e-23 | +0.25 | 1.6e-05 | 14 | supported | Structure ↗ |
| KRAS | AF-M | -0.53 | 1.1e-22 | +0.24 | 3.1e-05 | 14 | supported | Structure ↗ |
| RAP1A | AF-M | -0.60 | 2.2e-22 | +0.31 | 2.0e-04 | 10 | supported | Structure ↗ |
| PPP1CB | RF2-PPI | +1.91 | 2.7e-22 | -0.50 | 4.2e-07 | 7 | supported | Structure ↗ |
| HRAS | PDB | -1.14 | 5.3e-22 | +0.15 | 0.015 | 6 | supported | Structure ↗ |
| MRAS | AF-M | -0.62 | 3.9e-21 | +0.21 | 2.1e-04 | 10 | supported | Structure ↗ |
| RRAS2 | AF-M | -0.53 | 1.1e-20 | +0.22 | 1.5e-04 | 13 | supported | Structure ↗ |
| HRAS | AF-M | -0.53 | 1.1e-19 | +0.25 | 1.3e-04 | 14 | supported | Structure ↗ |
| YWHAB res 142-611 | AF-M | +2.00 | 5.5e-18 | -0.42 | 9.0e-05 | 7 | supported | Structure ↗ |
| YWHAB STKc_C-Raf | AF-M | +1.02 | 0.075 | -0.67 | 5.6e-17 | 10 | supported | Structure ↗ |
| RAP2A | AF-M | -0.58 | 5.7e-15 | +0.37 | 1.8e-05 | 8 | supported | Structure ↗ |
| SFN C1_A_C-Raf | AF-M | +1.62 | 4.4e-12 | -0.49 | 3.0e-08 | 9 | supported | Structure ↗ |
| HSP90AB1 | PDB | -0.02 | 0.002 | -0.55 | 6.8e-10 | 6 | supported | Structure ↗ |
| NDUFA10 res 94-522 | AF-M | +0.34 | 3.2e-07 | +0.35 | 1.1e-09 | 21 | supported | Structure ↗ |
| TAOK1 | AF-M | -0.42 | 3.3e-09 | -0.14 | 0.009 | 9 | supported | Structure ↗ |
| MAP2K6 | AF-M | -0.37 | 5.0e-09 | -0.30 | 1.7e-06 | 9 | supported | Structure ↗ |
| GNB2 | RF2-PPI | -0.47 | 1.5e-08 | +0.22 | 0.011 | 9 | supported | Structure ↗ |
| MAP2K3 | AF-M | -0.34 | 4.3e-08 | -0.31 | 2.2e-06 | 9 | supported | Structure ↗ |
| NR3C1 C1_A_C-Raf | AF-M | -0.59 | 6.6e-08 | -0.01 | 0.482 | 5 | supported | Structure ↗ |
| MAP3K1 | AF-M | -0.34 | 1.5e-07 | -0.20 | 0.006 | 7 | supported | Structure ↗ |
| MEK1 | PDB | -0.08 | 1.2e-04 | -0.27 | 8.4e-07 | 18 | supported | Structure ↗ |
| MEK1 | RF2-PPI | -0.33 | 2.7e-06 | -0.25 | 1.4e-04 | 9 | supported | Structure ↗ |
| MAP2K5 | AF-M | -0.29 | 5.1e-06 | -0.26 | 8.0e-06 | 10 | supported | Structure ↗ |
| A0A1B0GUL7 | RF2-PPI | -0.28 | 2.3e-04 | -0.27 | 2.1e-04 | 7 | supported | Structure ↗ |
| CSNK1G1 | AF-M | +0.89 | 7.4e-04 | -0.25 | 7.0e-04 | 10 | supported | Structure ↗ |
| JAK2 | AF-M | -0.23 | 7.1e-04 | -0.03 | 0.503 | 13 | supported | Structure ↗ |
| MEK1 | AF-M | -0.20 | 0.001 | -0.05 | 0.127 | 13 | supported | Structure ↗ |
| NR3C1 STKc_C-Raf | AF-M | +0.09 | 0.686 | -0.27 | 0.002 | 6 | supported | Structure ↗ |
| SFN res 612-622 | AF-M | -0.25 | 0.047 | -0.30 | 0.003 | 4 | supported | Structure ↗ |
| STK3 STKc_C-Raf | AF-M | -0.28 | 0.007 | -0.25 | 0.005 | 4 | supported | Structure ↗ |
| LSM14A | AF-M | +0.48 | 0.027 | -0.24 | 0.055 | 4 | supported | Structure ↗ |
| LOC113496266 | PDB | -0.22 | 0.046 | -0.03 | 0.827 | 6 | supported | Structure ↗ |
| MEK2 | RF2-PPI | -0.05 | 0.298 | -0.16 | 0.001 | 18 | not supported | Structure ↗ |
| MEK2 | AF-M | -0.11 | 0.009 | -0.13 | 0.013 | 16 | not supported | Structure ↗ |
| NDUFA10 C1_A_C-Raf | AF-M | +0.45 | 0.055 | +0.13 | 0.351 | 5 | not supported | Structure ↗ |