MAPK variant effect atlas
Proteins / KSR2

KSR2

Kinase suppressor of Ras 2

Scaffold pseudokinase UniProt Q6VAB6 HSP90 client (literature): strong 3D structure ↓ 9 interaction partners · volcano ↗
Mutagenized 2–485Mutagenized 487–950SAM 24–152SAMCRD 408–464Kinase 665–934Kinase1950 aagrey box: mutagenized region

MAPK pathway activity (phosphorylated ERK2 reporter) under basal conditions. Scores are WT-relative: 1 = wild type.

20,940 variantsmissense decreased 8% · increased 26%
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.
Domain Secondary structure Relative SASA pLDDT Curated feature Annotated interface Active site Inter-domain contact HSP90 contact CDC37 contact 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 * -
SAM CRD Kinase 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340 360 380 400 420 440 460 480 500 520 540 560 580 600 620 640 660 680 700 720 740 760 780 800 820 840 860 880 900 920 940 0.50 1.00 2.02
Click a position for its interactions and annotations — ■ the Interface strip marks positions in ≥1 supported interface (darker = more partners)

Structure · KSR2 alone

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Interfaces of KSR2

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
MEK1AF-M+0.928.5e-51-0.841.1e-3816supportedStructure ↗
MEK2AF-M+0.923.7e-49-0.846.2e-3817supportedStructure ↗
KSR1AF-M-0.691.2e-36+0.611.8e-1218supportedStructure ↗
MEK1PDB+0.531.8e-21-0.742.1e-3518supportedStructure ↗
BRAFAF-M-0.665.2e-33+0.581.6e-1020supportedStructure ↗
PRKAA1
res 22-687
AF-M-0.662.5e-26+1.124.6e-1015supportedStructure ↗
SOX2AF-M-1.002.2e-24+0.831.4e-125supportedStructure ↗
FBXL2RF2-PPI-1.022.8e-23+0.220.0514supportedStructure ↗
BRAFRF2-PPI-0.728.1e-23+0.591.1e-1211supportedStructure ↗
ARAFAF-M-0.638.2e-22+0.574.1e-1114supportedStructure ↗
CRAFAF-M-0.624.9e-19+0.554.0e-1011supportedStructure ↗
BRAF
SAM_KSR1_N
RF2-PPI-0.371.7e-06––10supportedStructure ↗
PRKAA1
res 469-776
AF-M-0.449.8e-05+0.130.7747supportedStructure ↗
CDC27RF2-PPI-0.030.782––5not supportedStructure ↗