- Fold
- Predicted membrane-associated — UniProt classifies it as a peripheral ER-membrane protein with a hydrophobic N-terminal segment annotated as a signal peptide (1–23), consistent with its reported ER-membrane and lipid-droplet localisation.
- Active-Site Region
- AstraBIND unclassified hypothesis (confidence 0.704) — a residue-level, substrate/cofactor-facing starting point for docking / mutagenesis; no validated ligand.
- Clean Signal
- One aggregation-prone segment flagged (AstraUNFOLD amyloid max 0.533) — worth screening in construct design.
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
Most tractable enzyme families have been structurally explored. METTL7B (also catalogued as thiol S-methyltransferase TMT1B) has not: an IDG Tbio target with no experimental structure in the PDB and only a handful of functional studies. It is reported to transfer a methyl group from S-adenosyl-L-methionine onto small-molecule thiol acceptors — metabolising substrates such as hydrogen sulfide and the drug captopril — and to sit on the endoplasmic-reticulum membrane and lipid droplets. Interest is real (oncology and lipid metabolism), yet there is almost nothing to look up.
That combination — genuine interest, near-zero structural information — is where prediction earns its keep: everything below is computed from the canonical 244-residue sequence with Orbion's Astra suite, with no experimental METTL7B structure used as input. For a target this dark, there is no structure to consult.
Architecture & Topology
How the Sequence Is Organised
| Element | Residues | Note |
|---|---|---|
| Signal Peptide | 1–23 | UniProt. |
The Predicted Pocket
The Predicted Active-Site Region
A residue-level binding hypothesis from AstraBIND (confidence 0.704, HIGH). AstraBIND is retrieval-based: candidate binders are drawn from public panels (PDB, IUPHAR, ChEMBL, homology), not designed de novo. Treat these as a starting point for docking / mutagenesis, not a validated ligand or a proven druggable site.
Site: Predicted substrate / cofactor-facing residues
Post-Translational & Structural Features
Specific, Testable Residues
- Aggregation-prone segment flagged (AstraUNFOLD amyloid max 0.533) — a short hydrophobic stretch worth screening or engineering out when designing a soluble construct for expression.
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 |
|---|---|---|
| Active-Site Region Residues | Alanine scan at the predicted site + thiol S-methyltransferase assay (SAM donor, thiol acceptor such as hydrogen sulfide) | Loss of methyl-transfer activity at the predicted site |
| Disordered / Flexible Regions | Fusion-partner insertion or terminal truncation | Improved expression / thermostability for structural work |
| Predicted Peripheral Membrane Association | Protease-protection / membrane-fractionation assay | Confirm ER-membrane / lipid-droplet association |
Scope & Limitations
What This Is — and Isn't
- Prediction, not experiment. These are computational hypotheses to prioritise experiments — not a structure or an assay. Nothing here is wet-lab validated.
- The pocket is predicted; the ligand is not named. AstraBIND is retrieval-based; the honest output is a residue-level hypothesis, not a proven druggable site or a validated binder.
- Largely correlative disease biology. METTL7B's oncology rationale rests on expression and knock-down studies — required for proliferation and tumorigenesis in non-small-cell lung cancer, and linked to Golgi integrity and invasion in breast cancer via RhoBTB1 — rather than a validated driver mechanism, and there is no Mendelian disease gene. Its alkyl-thiol / xenobiotic-methylation activity is biochemically reported but its role in tumour biology is unsettled. Treat the therapeutic case as a hypothesis.
All predictions were generated with Orbion's Astra suite from the canonical METTL7B sequence (UniProt Q6UX53), using AlphaFold-derived structural features. Reported values are model outputs; model internals are out of scope.
References
- [1]UniProt Consortium. UniProtKB entry Q6UX53 (METTL7B, human). uniprot.org.
- [2]Pharos (Illuminating the Druggable Genome). METTL7B target record — Tbio. pharos.nih.gov.
- [3]McKinnon CM et al. The tumor suppressor RhoBTB1 controls Golgi integrity and breast cancer cell invasion through METTL7B. (2017). https://doi.org/10.1186/s12885-017-3138-3
- [4]Liu D et al. METTL7B Is Required for Cancer Cell Proliferation and Tumorigenesis in Non-Small Cell Lung Cancer. (2020). https://doi.org/10.3389/fphar.2020.00178
- [5]Maldonato BJ et al. Human METTL7B is an alkyl thiol methyltransferase that metabolizes hydrogen sulfide and captopril. (2021). https://doi.org/10.1038/s41598-021-84218-5