Proteins / EGFR
EGFR
Epidermal growth factor receptor
Receptor tyrosine kinase
UniProt P00533
HSP90 client (literature): non
3D structure ↓
47 interaction partners · volcano ↗
MAPK pathway activity (phosphorylated ERK2 reporter) under basal conditions. Scores are WT-relative: 1 = wild type.
10,256 variantsmissense decreased 35% · increased 7%351 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 | |
|---|---|---|---|---|---|---|---|---|
| CTR9 | RF2-PPI | +0.79 | 2.4e-48 | +0.22 | 0.002 | 21 | supported | Structure ↗ |
| CHIA | RF2-PPI | +1.12 | 7.6e-33 | +0.10 | 0.541 | 6 | supported | Structure ↗ |
| EPS15 | RF2-PPI | -1.23 | 3.4e-31 | +0.49 | 1.9e-09 | 9 | supported | Structure ↗ |
| ITGB2 | RF2-PPI | -1.23 | 8.6e-29 | +0.28 | 9.7e-04 | 9 | supported | Structure ↗ |
| ERBB2 | AF-M | -0.87 | 1.0e-25 | +0.25 | 2.4e-04 | 16 | supported | Structure ↗ |
| JPH1 | RF2-PPI | +0.83 | 6.2e-22 | +0.01 | 0.537 | 7 | supported | Structure ↗ |
| NCK1 | RF2-PPI | -1.63 | 7.2e-21 | +0.49 | 2.9e-04 | 3 | supported | Structure ↗ |
| PPIB | AF-M | -0.84 | 9.4e-18 | +0.37 | 2.2e-04 | 7 | supported | Structure ↗ |
| GATB | RF2-PPI | -0.82 | 9.5e-18 | +0.52 | 4.8e-09 | 6 | supported | Structure ↗ |
| ADAMTS9 res 694-1073 | RF2-PPI | +0.54 | 2.4e-17 | +0.25 | 3.9e-04 | 12 | supported | Structure ↗ |
| LRIG3 | RF2-PPI | -1.04 | 3.3e-17 | +0.38 | 6.0e-05 | 7 | supported | Structure ↗ |
| NOTCH2 PTKc_EGFR #2 | RF2-PPI | -0.72 | 3.6e-17 | -0.05 | 0.969 | 13 | supported | Structure ↗ |
| ARAF | RF2-PPI | -1.05 | 1.6e-16 | +0.41 | 1.0e-05 | 7 | supported | Structure ↗ |
| SH2B3 | RF2-PPI | -0.59 | 1.8e-07 | -0.77 | 3.7e-16 | 10 | supported | Structure ↗ |
| IARS1 | RF2-PPI | +0.62 | 9.7e-16 | +0.17 | 0.092 | 13 | supported | Structure ↗ |
| PIK3R4 | RF2-PPI | +0.61 | 1.1e-15 | +0.21 | 0.009 | 11 | supported | Structure ↗ |
| LSM11 | RF2-PPI | -1.28 | 1.3e-15 | +1.10 | 2.5e-15 | 3 | supported | Structure ↗ |
| BUB3 | RF2-PPI | +0.97 | 1.9e-15 | +0.15 | 0.445 | 4 | supported | Structure ↗ |
| SEL1L | RF2-PPI | -0.75 | 5.7e-14 | +0.27 | 0.003 | 10 | supported | Structure ↗ |
| EGF PTKc_EGFR | AF-M | -0.74 | 3.4e-12 | +0.14 | 0.153 | 10 | supported | Structure ↗ |
| CLP1 | RF2-PPI | +0.46 | 4.3e-12 | +0.27 | 3.2e-04 | 11 | supported | Structure ↗ |
| MLST8 | RF2-PPI | +0.77 | 4.8e-12 | -0.05 | 0.467 | 4 | supported | Structure ↗ |
| ITGA2B | RF2-PPI | +0.57 | 1.4e-11 | +0.07 | 0.887 | 8 | supported | Structure ↗ |
| SOS1 | RF2-PPI | +0.56 | 3.6e-11 | +0.10 | 0.061 | 9 | supported | Structure ↗ |
| ERRFI1 | AF-M | -0.57 | 5.9e-11 | +0.19 | 2.2e-04 | 24 | supported | Structure ↗ |
| ERBB3 | PDB | -0.22 | 0.001 | +0.30 | 2.0e-10 | 20 | supported | Structure ↗ |
| KAT7 | RF2-PPI | +0.54 | 3.4e-10 | +0.23 | 0.004 | 9 | supported | Structure ↗ |
| ERRFI1 | PDB | -0.48 | 7.7e-10 | +0.25 | 3.4e-05 | 18 | supported | Structure ↗ |
| SGSM2 PTKc_EGFR | AF-M | -0.58 | 2.9e-09 | +0.41 | 9.2e-06 | 9 | supported | Structure ↗ |
| PLAA | RF2-PPI | +0.54 | 8.3e-09 | +0.17 | 0.451 | 4 | supported | Structure ↗ |
| FERMT1 | RF2-PPI | -0.05 | 0.875 | +0.51 | 2.1e-08 | 6 | supported | Structure ↗ |
| CTNND1 | RF2-PPI | +0.52 | 2.4e-08 | +0.14 | 0.290 | 8 | supported | Structure ↗ |
| SGSM2 PTKc_EGFR #2 | AF-M | -0.79 | 1.8e-07 | +0.62 | 2.2e-06 | 4 | supported | Structure ↗ |
| MYO9A | RF2-PPI | -0.60 | 2.6e-07 | +0.29 | 0.001 | 9 | supported | Structure ↗ |
| CBLC | RF2-PPI | +0.28 | 0.044 | +0.50 | 5.2e-07 | 5 | supported | Structure ↗ |
| B4GALT1 | RF2-PPI | -0.93 | 5.3e-07 | +0.38 | 0.008 | 3 | supported | Structure ↗ |
| CRKL | RF2-PPI | +0.57 | 1.1e-06 | -0.05 | 0.519 | 3 | supported | Structure ↗ |
| VAV2 | RF2-PPI | -0.01 | 0.556 | -0.68 | 1.2e-06 | 4 | supported | Structure ↗ |
| WDR44 | RF2-PPI | +0.33 | 2.7e-06 | +0.25 | 0.004 | 12 | supported | Structure ↗ |
| CTNNB1 | RF2-PPI | +0.51 | 4.4e-06 | +0.41 | 7.1e-04 | 4 | supported | Structure ↗ |
| ACOT9 | RF2-PPI | +0.34 | 4.9e-06 | +0.16 | 0.185 | 6 | supported | Structure ↗ |
| NOTCH2 PTKc_EGFR #3 | RF2-PPI | -0.23 | 0.033 | +0.54 | 1.5e-05 | 4 | supported | Structure ↗ |
| LRIG1 | RF2-PPI | -0.47 | 1.9e-05 | +0.32 | 6.1e-04 | 8 | supported | Structure ↗ |
| SOS2 PTKc_EGFR | RF2-PPI | -0.48 | 8.8e-05 | +0.26 | 0.016 | 8 | supported | Structure ↗ |
| ERBB3 | AF-M | -0.29 | 1.1e-04 | +0.19 | 1.4e-04 | 19 | supported | Structure ↗ |
| EED | RF2-PPI | +0.12 | 0.101 | +0.44 | 5.1e-04 | 3 | supported | Structure ↗ |
| MIOS | RF2-PPI | -0.10 | 0.902 | +0.33 | 5.1e-04 | 6 | supported | Structure ↗ |
| ANKRD13A | RF2-PPI | +0.25 | 7.1e-04 | +0.28 | 0.008 | 8 | supported | Structure ↗ |
| CD2AP | RF2-PPI | -0.44 | 0.001 | -0.05 | 0.678 | 10 | supported | Structure ↗ |
| SOS2 PTKc_EGFR #2 | RF2-PPI | -0.49 | 0.003 | +0.35 | 0.015 | 4 | supported | Structure ↗ |
| PTPRF | RF2-PPI | +0.44 | 0.003 | -0.16 | 0.061 | 5 | supported | Structure ↗ |
| EGFR PTKc_EGFR #2 | PDB | +0.13 | 0.190 | -0.43 | 0.008 | 4 | supported | Structure ↗ |
| EGFR PTKc_EGFR | PDB | -0.08 | 0.069 | -0.04 | 0.482 | 11 | supported | Structure ↗ |
| ABL1 | AF-M | +0.34 | 0.320 | -0.18 | 0.071 | 4 | not supported | Structure ↗ |
| EGF PTKc_EGFR #2 | AF-M | +0.19 | 0.110 | +0.20 | 0.201 | 5 | not supported | Structure ↗ |
| NOTCH2 PTKc_EGFR | RF2-PPI | -0.02 | 0.893 | -0.12 | 0.247 | 5 | not supported | Structure ↗ |
| TWF1 | RF2-PPI | -0.07 | 0.694 | -0.20 | 0.357 | 3 | not supported | Structure ↗ |
| JUP | RF2-PPI | +0.07 | 0.419 | +0.07 | 0.976 | 9 | not supported | Structure ↗ |
| ADAMTS9 PTKc_EGFR | RF2-PPI | +0.12 | 0.526 | -0.05 | 0.617 | 6 | not supported | Structure ↗ |
| ATP6V1H | RF2-PPI | +0.05 | 0.764 | +0.02 | 0.828 | 4 | not supported | Structure ↗ |