Proteins / SHP2
SHP2
Tyrosine-protein phosphatase non-receptor type 11 · gene PTPN11
Phosphatase
UniProt Q06124
HSP90 client (literature): unknown
3D structure ↓
15 interaction partners · volcano ↗
MAPK pathway activity (phosphorylated ERK2 reporter) under basal conditions. Scores are WT-relative: 1 = wild type.
12,609 variantsmissense decreased 43% · increased 19%2,771 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 | |
|---|---|---|---|---|---|---|---|---|
| GAB2 SH2_C-SH2_SHP_like #2 | AF-M | -0.38 | 2.1e-42 | -0.02 | 0.444 | 26 | supported | Structure ↗ |
| GAB1 | AF-M | -0.48 | 3.4e-42 | -0.10 | 0.079 | 18 | supported | Structure ↗ |
| GAB3 SH2_N-SH2_SHP_like | AF-M | -0.39 | 2.1e-40 | -0.05 | 0.255 | 25 | supported | Structure ↗ |
| GAB1 | PDB | -0.65 | 2.4e-27 | -0.13 | 0.456 | 9 | supported | Structure ↗ |
| GAB2 SH2_C-SH2_SHP_like | AF-M | -0.54 | 1.3e-26 | -0.01 | 0.523 | 14 | supported | Structure ↗ |
| SOS1 | AF-M | -0.45 | 5.2e-22 | +0.15 | 0.058 | 12 | supported | Structure ↗ |
| GAB3 | RF2-PPI | -0.48 | 7.3e-22 | -0.02 | 0.794 | 13 | supported | Structure ↗ |
| GAB3 SH2_C-SH2_SHP_like | AF-M | -0.63 | 3.6e-21 | -0.12 | 0.209 | 8 | supported | Structure ↗ |
| FRS2 | AF-M | -0.46 | 2.3e-20 | -0.03 | 0.606 | 12 | supported | Structure ↗ |
| THEMIS | AF-M | -0.27 | 1.7e-15 | -0.16 | 0.028 | 10 | supported | Structure ↗ |
| PDCD1 | PDB | -0.45 | 2.7e-15 | -0.09 | 0.917 | 7 | supported | Structure ↗ |
| CD28 | PDB | -0.86 | 1.2e-13 | -0.19 | 0.121 | 3 | supported | Structure ↗ |
| SOS1 | RF2-PPI | -0.26 | 2.2e-13 | +0.24 | 9.8e-04 | 11 | supported | Structure ↗ |
| GRB2 | AF-M | -0.24 | 8.0e-10 | +0.10 | 0.278 | 15 | supported | Structure ↗ |
| SOS2 | RF2-PPI | -0.18 | 2.0e-09 | +0.21 | 0.009 | 10 | supported | Structure ↗ |
| TXNIP | PDB | -0.38 | 9.1e-06 | -0.01 | 0.839 | 8 | supported | Structure ↗ |
| IRS1 | PDB | +0.11 | 1.3e-05 | -0.36 | 4.9e-04 | 5 | supported | Structure ↗ |
| IL6ST | RF2-PPI | +1.90 | 0.009 | -0.69 | 2.9e-04 | 3 | supported | Structure ↗ |
| SHP2 SH2_C-SH2_SHP_like | PDB | -0.06 | 0.199 | -0.29 | 7.6e-04 | 8 | supported | Structure ↗ |
| HDGF | RF2-PPI | +2.02 | 0.874 | -0.81 | 9.5e-04 | 3 | supported | Structure ↗ |
| SHP2 PTPc-N11 | PDB | -0.18 | 0.061 | -0.64 | 0.055 | 3 | supported | Structure ↗ |
| MPZL1 | AF-M | +0.04 | 1.5e-18 | +0.04 | 0.887 | 28 | not supported | Structure ↗ |
| MPZL1 | PDB | +0.16 | 3.0e-06 | -0.08 | 0.301 | 27 | not supported | Structure ↗ |
| cagA | PDB | -0.05 | 5.9e-05 | +0.06 | 0.438 | 5 | not supported | Structure ↗ |
| SHP2 PTPc-N11 #2 | PDB | +0.12 | 0.387 | +0.09 | 0.402 | 4 | not supported | Structure ↗ |
| FN1 | PDB | +0.22 | 0.952 | +0.05 | 0.469 | 3 | not supported | Structure ↗ |