- Fold
- Seven transmembrane helices; multi-pass plasma-membrane receptor; non-enzyme.
- Lipid-Facing Surface
- Predicted lipid-facing surface (AstraBIND confidence 0.679, medium). A residue-level membrane-interface hypothesis — a starting point for docking and mutagenesis, not a claim of an orthosteric drug pocket. No validated ligand.
- Structural Anchors
- Conserved TM3–ECL2 disulfide C96–C174; N-glycosylation at N3 and N184 (UniProt).
- Flexible Regions
- Elevated predicted disorder — disordered N-terminus (1–17), long intracellular loop (209–277) and C-tail (353–373) — the natural truncation boundaries for construct design.
- Clean Signal
- One aggregation-prone segment flagged (AstraUNFOLD max 0.536) — 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 receptor families have been structurally explored. GPR173 remains dark: an IDG Tbio class A GPCR with no experimental structure in the PDB and a thin primary literature. It is SREB3 — one of three super-conserved receptors expressed in brain — and is reported to be the receptor for the neuropeptide phoenixin, through which it augments gonadotropin-releasing-hormone signalling in the hypothalamus and pituitary and promotes granulosa-cell proliferation in the ovary. That pairing is largely inferred by similarity and from rodent and cell models, so even the receptor's pharmacology is unsettled.
That combination — genuine interest, near-zero structural information — is exactly where prediction earns its keep: everything below is computed from the canonical 373-residue sequence with Orbion's Astra suite, with no experimental GPR173 structure or validated ligand used as input. For a genuine orphan, there is nothing to look up.
Architecture & Topology
How the Sequence Is Organised
| Element | Residues | Note |
|---|---|---|
| Transmembrane Helices | 7 predicted | Boundaries: 27–47; 60–80; 98–118; 140–160; 189–209; 288–308; 323–343. |
The Predicted Pocket
A Predicted Lipid-Facing Surface
AstraBIND classifies this as a membrane-mimetic / lipid-facing surface, not an orthosteric pocket — so we present it as a membrane-interface hypothesis only, and a low-confidence one (no ligand-bound relative to retrieve from). It is an exploratory surface for mutagenesis, not a validated ligand site or a druggable pocket.
Site: Membrane-facing / lipid interface (transmembrane surface)
Post-Translational & Structural Features
Specific, Testable Residues
- Disulfide bond C96–C174. Annotated in UniProt (rule-based); the conserved class A TM3–ECL2 bridge that caps the pocket — a fold sanity-check and a Cys→Ala mutagenesis handle.
- N-glycosylation at position 3, 184 — on the extracellular N-terminus and ECL2 (UniProt).
- Aggregation-prone segment flagged (AstraUNFOLD amyloid max 0.536) — a modest aggregation liability worth screening during construct design.
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 |
|---|---|---|
| Lipid-Facing Surface Residues (TM3, TM6, TM7) | Alanine scan + docking at the predicted membrane-facing site | Binding or SAR at the predicted surface |
| Disulfide C96–C174 | Cys→Ala mutagenesis (C96A, C174A) | Expression / fold loss — fold-integrity check |
| Disordered ICL3 (209–277) and C-Tail (353–373) | Fusion-partner insertion or terminal truncation | Expression / thermostability for structural work |
| Reported Phoenixin Receptor Activity | Phoenixin-14 / -20 challenge in a GnRH / kisspeptin neuron model | Confirm receptor–peptide coupling |
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 site is predicted; no ligand is named. AstraBIND is retrieval-based, and here it flags a lipid-facing surface rather than a classical orthosteric pocket — a residue-level hypothesis, not a proven druggable site or a validated binder.
- Reproductive biology inferred, not proven here. GPR173's phoenixin pairing and its roles in GnRH / kisspeptin signalling and folliculogenesis come from rodent and cell-model studies and by-similarity annotation, not from a solved human receptor–ligand complex. Treat the therapeutic case as a hypothesis.
All predictions were generated with Orbion's Astra suite from the canonical GPR173 sequence (UniProt Q9NS66), using AlphaFold-derived structural features. Reported values are model outputs; model internals are out of scope.
References
- [1]UniProt Consortium. UniProtKB entry Q9NS66 (GPR173, human). uniprot.org.
- [2]Pharos (Illuminating the Druggable Genome). GPR173 target record — Tbio. pharos.nih.gov.
- [3]Treen AK et al. Phoenixin Activates Immortalized GnRH and Kisspeptin Neurons Through the Novel Receptor GPR173. (2016). https://doi.org/10.1210/me.2016-1039
- [4]Stein LM et al. Hypothalamic action of phoenixin to control reproductive hormone secretion in females: importance of the orphan G protein-coupled receptor Gpr173. (2016). https://doi.org/10.1152/ajpregu.00191.2016
- [5]Nguyen XP et al. Effect of the neuropeptide phoenixin and its receptor GPR173 during folliculogenesis. (2019). https://doi.org/10.1530/rep-19-0025