Proteins / RET
RET
Proto-oncogene tyrosine-protein kinase receptor Ret
Receptor tyrosine kinase
UniProt P07949
HSP90 client (literature): weak
3D structure ↓
6 interaction partners · volcano ↗
MAPK pathway activity (phosphorylated ERK2 reporter) under basal conditions. Scores are WT-relative: 1 = wild type.
10,106 variantsmissense decreased 25% · increased 12%1,634 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 | |
|---|---|---|---|---|---|---|---|---|
| RET | PDB | -0.20 | 1.3e-28 | +0.46 | 1.7e-19 | 20 | supported | Structure ↗ |
| RAPH1 | RF2-PPI | +0.21 | 3.1e-21 | -0.12 | 0.468 | 6 | supported | Structure ↗ |
| SORL1 PTKc_RET #2 | RF2-PPI | -0.25 | 3.2e-16 | +0.04 | 0.609 | 7 | supported | Structure ↗ |
| PLCG1 | AF-M | +0.19 | 4.1e-12 | -0.55 | 8.7e-13 | 8 | supported | Structure ↗ |
| PTPRA | RF2-PPI | -0.20 | 1.3e-07 | +0.35 | 0.005 | 5 | supported | Structure ↗ |
| SORL1 PTKc_RET | RF2-PPI | -0.22 | 9.8e-07 | -0.19 | 0.095 | 8 | supported | Structure ↗ |
| NTRK1 | AF-M | -0.14 | 0.730 | -0.29 | 0.019 | 3 | supported | Structure ↗ |
| GNPTAB | RF2-PPI | +0.13 | 2.1e-22 | -0.11 | 0.319 | 8 | not supported | Structure ↗ |
| CBLC | RF2-PPI | +0.17 | 5.6e-15 | -0.12 | 0.207 | 4 | not supported | Structure ↗ |
| GFRA1 | AF-M | -0.14 | 0.173 | -0.17 | 0.258 | 4 | not supported | Structure ↗ |