MAPK variant effect atlas
Proteins / MEK2

MEK2

Dual specificity mitogen-activated protein kinase kinase 2 · gene MAP2K2

MEK kinase UniProt P36507 HSP90 client (literature): non 3D structure ↓ 14 interaction partners · volcano ↗
Mutagenized 2–400Kinase 68–400Kinase1400 aagrey box: mutagenized region

Abundance under HSP90 inhibition (pimitespib). The HSP90 calls compare each variant's inhibited and untreated abundance. Scores are WT-relative: 1 = wild type.

8,551 variantsmissense decreased 36% · increased 2%HSP90-dependent 39% of missense & deletionsbuffered 23% · poorly buffered 16% · WT-like or increased 62%
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 buffered
0%25%50%75%100%
Fraction of variants at this position that are buffered: wild-type-like untreated but decreased under HSP90 inhibition (HSP90i condition only).
Fraction HSP90-dependent
0%25%50%75%100%
Fraction of variants at this position whose abundance falls under HSP90 inhibition by at least the wild-type-to-synonymous gap (the paper's dependence call; HSP90i condition only).
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.
Domain Secondary structure Relative SASA pLDDT Curated feature Annotated interface Active site Inter-domain contact HSP90 contact CDC37 contact Fraction buffered Fraction HSP90-dependent Fraction decreased Fraction increased Interface A V I L G F Y W C M P S T N Q D E H K R * -
Kinase 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340 360 380 400 0.08 1.00 2.00
Click a position for its interactions and annotations — ■ the Interface strip marks positions in ≥1 supported interface (darker = more partners)

Structure · MEK2 alone

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Interfaces of MEK2

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.

PartnerSourceActivity dq Abundance dqInterface positionsSupported
MAP2K5
PKc_MAP2K2 #2
AF-M+0.732.3e-09+0.370.0193supportedStructure ↗
MAP2K5
PKc_MAP2K2
AF-M+0.536.6e-08+0.300.1203supportedStructure ↗
CRAFAF-M-0.267.4e-07+0.160.11715supportedStructure ↗
BRAFAF-M-0.211.5e-05+0.200.03413supportedStructure ↗
STK26AF-M-0.331.6e-05+0.140.31911supportedStructure ↗
KSR2AF-M-0.255.4e-05+0.100.48715supportedStructure ↗
RHOBTB2RF2-PPI+0.288.2e-05+0.270.0804supportedStructure ↗
ARAFAF-M-0.221.5e-04+0.150.21715supportedStructure ↗
KSR1AF-M-0.225.4e-04+0.140.22917supportedStructure ↗
MEK1AF-M+0.260.001+0.130.52312supportedStructure ↗
MAPK8AF-M-0.270.002+0.070.9638supportedStructure ↗
MAP3K2RF2-PPI-0.220.012+0.120.7006supportedStructure ↗
MAPK3RF2-PPI+0.130.031+0.240.0198supportedStructure ↗
MAPK1AF-M-0.020.036+0.140.09511supportedStructure ↗
MAP4K5AF-M-0.030.065+0.120.45110supportedStructure ↗
MEK2PDB+0.018.0e-05+0.150.18012not supportedStructure ↗
CRAFRF2-PPI-0.190.002+0.130.16818not supportedStructure ↗
BRAFRF2-PPI-0.140.009+0.150.34011not supportedStructure ↗
MAP3K1RF2-PPI-0.040.012+0.080.94511not supportedStructure ↗
MAPK3AF-M-0.120.014+0.180.08811not supportedStructure ↗
MAP3K7AF-M-0.130.024+0.180.06218not supportedStructure ↗
BBS7RF2-PPI+0.190.028+0.010.46710not supportedStructure ↗
MAPK1RF2-PPI+0.140.059+0.200.1036not supportedStructure ↗
ARAFRF2-PPI-0.090.065+0.090.40117not supportedStructure ↗
MOSAF-M-0.020.110+0.120.40111not supportedStructure ↗
PGRMC1RF2-PPI+0.100.258+0.160.2667not supportedStructure ↗
MOSRF2-PPI-0.020.673+0.170.2678not supportedStructure ↗
WDR83AF-M-0.060.364-0.010.30511not supportedStructure ↗
MAP2K3AF-M+0.040.422+0.090.7847not supportedStructure ↗
MAPK8RF2-PPI-0.130.470-0.000.46514not supportedStructure ↗