Proteins / MEK1
MEK1
Dual specificity mitogen-activated protein kinase kinase 1 · gene MAP2K1
MEK kinase
UniProt Q02750
HSP90 client (literature): non
3D structure ↓
11 interaction partners · volcano ↗
MAPK pathway activity (phosphorylated ERK2 reporter) under basal conditions. Scores are WT-relative: 1 = wild type.
8,699 variantsmissense decreased 11% · increased 21%
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 | |
|---|---|---|---|---|---|---|---|---|
| KSR1 | PDB | -0.24 | 1.5e-10 | +0.05 | 0.290 | 16 | supported | Structure ↗ |
| MAPK1 | RF2-PPI | +0.20 | 1.7e-08 | -0.13 | 0.628 | 7 | supported | Structure ↗ |
| MEK1 PKc_MAP2K1 | PDB | +0.16 | 1.3e-07 | -0.05 | 0.623 | 12 | supported | Structure ↗ |
| PLEKHF2 | RF2-PPI | +0.43 | 2.0e-07 | +0.06 | 0.976 | 3 | supported | Structure ↗ |
| MEK2 | AF-M | +0.26 | 3.2e-06 | -0.07 | 0.494 | 12 | supported | Structure ↗ |
| KSR1 | AF-M | -0.24 | 9.2e-06 | +0.06 | 0.290 | 16 | supported | Structure ↗ |
| MAPK1 | AF-M | +0.16 | 9.7e-06 | -0.03 | 0.379 | 12 | supported | Structure ↗ |
| MAP3K1 | RF2-PPI | +0.24 | 1.5e-05 | -0.12 | 0.159 | 11 | supported | Structure ↗ |
| KSR2 | AF-M | -0.21 | 3.7e-05 | +0.03 | 0.523 | 14 | supported | Structure ↗ |
| KSR2 | PDB | -0.18 | 3.8e-05 | +0.01 | 0.687 | 15 | supported | Structure ↗ |
| BRAF | AF-M | -0.23 | 3.9e-05 | +0.04 | 0.400 | 12 | supported | Structure ↗ |
| CRAF | AF-M | -0.23 | 1.6e-04 | +0.05 | 0.446 | 12 | supported | Structure ↗ |
| PEBP4 | RF2-PPI | -0.26 | 0.001 | -0.24 | 0.019 | 5 | supported | Structure ↗ |
| ARAF | AF-M | -0.18 | 0.001 | +0.04 | 0.451 | 14 | supported | Structure ↗ |
| CRAF | PDB | -0.15 | 1.4e-06 | +0.05 | 0.173 | 15 | not supported | Structure ↗ |
| MEK1 PKc_MAP2K1 #2 | PDB | +0.10 | 8.9e-05 | -0.07 | 0.870 | 10 | not supported | Structure ↗ |
| MAPK3 | AF-M | +0.13 | 1.8e-04 | +0.07 | 0.173 | 12 | not supported | Structure ↗ |
| BRAF | PDB | -0.15 | 2.6e-04 | +0.07 | 0.253 | 18 | not supported | Structure ↗ |
| CRAF | RF2-PPI | -0.16 | 0.001 | +0.06 | 0.432 | 10 | not supported | Structure ↗ |
| TRIB1 | RF2-PPI | +0.05 | 0.010 | +0.02 | 0.739 | 5 | not supported | Structure ↗ |
| MAPK3 | RF2-PPI | +0.04 | 0.029 | -0.13 | 1.000 | 6 | not supported | Structure ↗ |
| MAP3K8 | AF-M | -0.16 | 0.029 | +0.03 | 0.503 | 9 | not supported | Structure ↗ |
| MAP3K8 | RF2-PPI | +0.08 | 0.053 | -0.17 | 0.249 | 7 | not supported | Structure ↗ |
| MAP3K1 | AF-M | +0.02 | 0.073 | -0.11 | 0.455 | 8 | not supported | Structure ↗ |
| MAP2K6 | AF-M | -0.02 | 0.087 | -0.11 | 0.579 | 5 | not supported | Structure ↗ |
| MAPK3 | PDB | +0.01 | 0.101 | -0.03 | 0.870 | 22 | not supported | Structure ↗ |
| 14-3-3zeta | PDB | -0.10 | 0.101 | -0.16 | 0.434 | 4 | not supported | Structure ↗ |
| MAP3K2 | RF2-PPI | +0.09 | 0.130 | -0.12 | 0.229 | 13 | not supported | Structure ↗ |
| MEK1 PKc_MAP2K1 #3 | PDB | -0.08 | 0.154 | +0.04 | 0.732 | 6 | not supported | Structure ↗ |
| MAP3K3 | RF2-PPI | -0.08 | 0.159 | -0.05 | 0.898 | 10 | not supported | Structure ↗ |
| STK11 | AF-M | +0.04 | 0.171 | -0.06 | 0.816 | 7 | not supported | Structure ↗ |
| MEK1 PKc_MAP2K1 #4 | PDB | -0.05 | 0.173 | +0.09 | 0.358 | 5 | not supported | Structure ↗ |
| ARAF | RF2-PPI | -0.15 | 0.203 | -0.01 | 0.877 | 8 | not supported | Structure ↗ |
| MAP3K4 | AF-M | -0.05 | 0.209 | -0.05 | 0.866 | 8 | not supported | Structure ↗ |
| MAP3K7 | AF-M | +0.00 | 0.257 | +0.05 | 0.344 | 17 | not supported | Structure ↗ |
| WDR83 | AF-M | -0.11 | 0.260 | -0.14 | 0.444 | 11 | not supported | Structure ↗ |
| WNK1 | AF-M | -0.05 | 0.730 | -0.17 | 0.324 | 6 | not supported | Structure ↗ |
| GRK2 | RF2-PPI | +0.09 | 0.456 | -0.14 | 0.917 | 4 | not supported | Structure ↗ |
| BRAF | RF2-PPI | +0.06 | 0.998 | -0.07 | 0.572 | 10 | not supported | Structure ↗ |