- Fold
- Soluble, predominantly ordered single chain built from six WD40 repeats — predicted to close into a seven-bladed β-propeller. Non-enzyme.
- Interaction Pocket
- High-confidence hypothesis (0.84). A residue-level pocket on the propeller face / central channel — the surface a WD40 scaffold uses to bind partners, and the one thing a fold alone does not tell you.
- Function Context
- Non-enzyme scaffold; recently implicated as an ATM-dependent genome-maintenance factor required for p53 accumulation.
- Flexible Regions
- Only ~8% disordered — a compact, ordered propeller, well-suited to structural work.
- Clean Signal
- No membrane, and no amyloidogenic segments predicted.
Model-reported confidence for the headline calls (amber = the load-bearing prediction the rest of the profile builds on). These are model-estimated probabilities that rank and gate each call — not calibrated rates of experimental success.
The Gap
Why This Target Is Still Dark
WDR89 is a paradox of the dark proteome: evolutionarily conserved yet almost entirely uncharacterised. It sits at IDG Tdark — essentially no dedicated primary literature, no known ligand, no experimental structure in the PDB. Until recently there was nothing to say about what it does. That changed in early 2026, when a Dependency-Map correlation analysis pulled WDR89 out of obscurity as a genome-maintenance factor: it relocalises to the nucleolus on DNA damage in an ATM-dependent manner, is required for p53 accumulation after irradiation, and its depletion increases DNA damage.
So interest is arriving faster than structural information exists. That is exactly where prediction earns its keep: everything below is computed from the canonical 387-residue sequence and derived structural predictions, with no experimental WDR89 structure used as input. For a newly-interesting orphan, there is nothing to look up.
Architecture & Topology
How the Sequence Is Organised
| Element | Residues | Note |
|---|---|---|
| WD40 repeats ×6 | 21–358 | Six ~40-residue repeats (21–65, 68–107, 112–156, 168–208, 214–254, 319–358) fold into the blades of the propeller. |
| C-terminal closure strand | 367–386 | The 'velcro' strand that closes the seven-bladed propeller; contributes pocket residues. |
The Predicted Pocket
The Predicted Interaction Pocket
A high-confidence pocket (0.84) on the propeller. Because the contributing residues are scattered across the sequence (WD4–WD5 loops and the C-terminal closure) but converge in space, the pocket is a spatial prediction, not a sequence artefact. For a scaffold protein, the pocket is the function — it is where WDR89 would recruit the partners implicated in its genome-maintenance role. No known binders — a genuine orphan surface.
Site: Propeller face / central channel (WD4–WD5 loops + C-terminal closure)
Post-Translational & Structural Features
Specific, Testable Residues
- Ubiquitination-rich. The dominant predicted modification — consistent with a protein whose abundance and DNA-damage response are regulated by the ubiquitin system.
- Phosphorylation sites. A smaller set of predicted phosphosites — candidate control points for the ATM-dependent, damage-induced relocalisation reported for WDR89.
- No membrane, disorder or amyloid signal. A clean, compact, ordered propeller — the whole chain is a viable target for structural work.
Recommended Experimental Follow-Up
An Orphan Sequence, Turned Into a Ranked Plan
Each prediction is paired with the experiment that would test it and the readout to watch for.
| Prediction | Experiment | Readout |
|---|---|---|
| Seven-bladed β-propeller fold | Limited proteolysis / recombinant expression of the propeller | A stable, well-behaved construct |
| Interaction pocket (WD4–WD5 + C-strand) | Alanine scan at the pocket + AP-MS partner mapping | Loss of specific partner binding |
| Genome-maintenance role | Pocket-mutant rescue of the DNA-damage / p53 phenotype | Which partners the pocket controls |
| Ubiquitination sites | Point mutants at predicted sites | Change in WDR89 stability / turnover |
| Phospho sites | Phosphomimetic / phospho-null mutants | Change in damage-induced relocalisation |
Scope & Limitations
What This Is — and Isn't
- Prediction, not experiment. These are computational hypotheses to prioritise experiments — not a substitute for a structure or an assay. No result here has been validated in the wet lab.
- The pocket is predicted; no binder is named. For a scaffold the honest output is a residue-level interaction-surface hypothesis, not a ligand or a proven complex.
- The seven-blade count is an inference. UniProt annotates six WD40 repeats; the seven-bladed β-propeller is the standard predicted fold for that architecture, not an explicit experimental fact. The genome-maintenance role rests on a single 2026 preprint — treat it as an emerging, not settled, function.
All predictions were generated with Orbion's Astra suite from the canonical WDR89 sequence (UniProt Q96FK6), using AlphaFold-derived structural features. Reported values are model outputs; model internals are out of scope.
References
- [1]UniProt Consortium. UniProtKB entry Q96FK6 (WDR89, human). uniprot.org.
- [2]Pharos / Illuminating the Druggable Genome. WDR89 target record — Tdark. pharos.nih.gov.
- [3]Minaker S.W., Negri G.L., Morin G.B., Stirling P.C. Dependency Map correlation analysis reveals WDR89 as a genome maintenance factor. bioRxiv 2026.01.28.698016 (2026; preprint). https://doi.org/10.64898/2026.01.28.698016