Proteins / GRB2
GRB2
Growth factor receptor-bound protein 2
Adapter
UniProt P62993
HSP90 client (literature): unknown
3D structure ↓
26 interaction partners · volcano ↗
MAPK pathway activity (phosphorylated ERK2 reporter) under basal conditions. Scores are WT-relative: 1 = wild type.
4,807 variantsmissense decreased 14% · increased 35%
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 | |
|---|---|---|---|---|---|---|---|---|
| LAT2 | AF-M | -1.65 | 7.3e-52 | -0.87 | 2.5e-12 | 8 | supported | Structure ↗ |
| PTPN6 | AF-M | -1.36 | 8.1e-42 | -0.69 | 6.8e-07 | 10 | supported | Structure ↗ |
| SHP2 | AF-M | -1.18 | 2.8e-39 | -0.78 | 1.0e-11 | 11 | supported | Structure ↗ |
| LAT | AF-M | -1.52 | 7.4e-38 | -1.15 | 3.8e-19 | 6 | supported | Structure ↗ |
| GAB3 | RF2-PPI | +0.57 | 3.5e-12 | +0.77 | 6.0e-27 | 13 | supported | Structure ↗ |
| ERRFI1 | AF-M | -0.10 | 0.327 | +1.09 | 1.5e-24 | 5 | supported | Structure ↗ |
| PTPN22 | RF2-PPI | -0.10 | 0.100 | +0.89 | 6.2e-24 | 7 | supported | Structure ↗ |
| PTPN22 | AF-M | -0.67 | 6.6e-24 | +0.16 | 0.013 | 18 | supported | Structure ↗ |
| ARHGAP12 | AF-M | -0.79 | 3.3e-22 | -0.07 | 0.272 | 12 | supported | Structure ↗ |
| TNK2 | AF-M | -0.80 | 8.0e-20 | -0.05 | 0.133 | 8 | supported | Structure ↗ |
| GAB2 | PDB | +1.21 | 9.0e-19 | +0.51 | 2.0e-05 | 6 | supported | Structure ↗ |
| BTK SH2_GRB2_like | AF-M | -1.32 | 6.7e-18 | -0.55 | 2.1e-05 | 4 | supported | Structure ↗ |
| NTRK3 SH2_GRB2_like | AF-M | -0.80 | 1.2e-17 | -0.78 | 1.1e-14 | 8 | supported | Structure ↗ |
| DLGAP1 | AF-M | -0.48 | 0.002 | +0.85 | 1.4e-15 | 5 | supported | Structure ↗ |
| THEMIS | AF-M | +0.58 | 3.6e-15 | +0.56 | 1.6e-10 | 15 | supported | Structure ↗ |
| DCTN1 | AF-M | -0.32 | 2.6e-07 | +0.81 | 3.7e-15 | 6 | supported | Structure ↗ |
| PAK2 | RF2-PPI | -0.00 | 0.814 | +0.56 | 7.7e-15 | 19 | supported | Structure ↗ |
| ARHGAP9 | AF-M | -0.72 | 3.8e-14 | -0.19 | 4.5e-06 | 10 | supported | Structure ↗ |
| RAPGEF1 | RF2-PPI | +0.01 | 0.714 | +0.81 | 4.7e-14 | 4 | supported | Structure ↗ |
| REPS2 | RF2-PPI | -0.00 | 0.821 | +0.80 | 1.2e-13 | 4 | supported | Structure ↗ |
| GRB2 SH2_GRB2_like | PDB | +0.50 | 4.7e-11 | -0.12 | 0.013 | 15 | supported | Structure ↗ |
| GAB2 | AF-M | -0.21 | 0.011 | +0.36 | 1.0e-10 | 16 | supported | Structure ↗ |
| VAV3 | AF-M | +0.69 | 1.8e-10 | +0.43 | 1.3e-07 | 9 | supported | Structure ↗ |
| GRB2 SH2_GRB2_like #3 | PDB | -0.59 | 1.6e-08 | +0.58 | 2.4e-07 | 8 | supported | Structure ↗ |
| PAK1 | AF-M | -0.43 | 2.1e-08 | -0.20 | 0.596 | 18 | supported | Structure ↗ |
| REPS1 | RF2-PPI | -0.12 | 0.193 | +0.54 | 4.7e-08 | 6 | supported | Structure ↗ |
| Vav1 | PDB | +0.55 | 1.0e-06 | +0.57 | 5.5e-08 | 9 | supported | Structure ↗ |
| DOCK1 | AF-M | -0.54 | 4.3e-07 | -0.23 | 0.556 | 8 | supported | Structure ↗ |
| THEMIS | PDB | +0.07 | 0.949 | +0.44 | 2.7e-06 | 13 | supported | Structure ↗ |
| GRB2 SH2_GRB2_like #2 | PDB | +0.40 | 3.6e-06 | -0.39 | 2.2e-04 | 6 | supported | Structure ↗ |
| NTRK3 SH3_GRB2_C | AF-M | -0.49 | 0.001 | +0.24 | 0.142 | 5 | supported | Structure ↗ |
| BTK SH3_GRB2_C | AF-M | +0.12 | 0.079 | +0.32 | 0.005 | 4 | supported | Structure ↗ |
| LRRK1 | AF-M | +0.17 | 0.165 | +0.13 | 0.123 | 8 | supported | Structure ↗ |