CG6836 encodes a 328-residue multi-pass membrane protein of the OST-alpha/TMEM184 family (Pfam Solute_trans_a), with seven predicted transmembrane helices, a predicted extracellular N-terminus carrying several N-glycosylation sequons and a cytoplasmic C-terminus. Phylogenetic analysis and Ensembl Compara place it in the OST-alpha (SLC51A) lineage rather than with the TMEM184 or Hfl1 proteins. It is therefore the fly counterpart of the vertebrate OST-alpha subunit, which pairs with OST-beta to form a facilitated-diffusion transporter for bile acids and steroid conjugates. No experimental work has been done on the fly protein. Its substrate, its partner requirement (no fly OST-beta is known), its subcellular location and its physiological role are all undetermined. Insects lack the vertebrate enterohepatic bile-acid circulation, and the ancestral substrates of the OST-alpha lineage are thought to be other steroid-like or lipid-derived solutes.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Plasma membrane is a reasonable OST-alpha ortholog inference, though it has not been tested in the fly. Reason: UniProt curators assign "Cell membrane" by similarity (ECO:0000250), and this IEA row maps that assignment to GO. The re-review tree places CG6836 in the OST-alpha (SLC51A) lineage, and Dawson et al. list FBgn0036834 among putative OST-alpha orthologs. Vertebrate OST-alpha works at the basolateral plasma membrane. The predicted topology (glycosylated extracellular N-terminus, seven transmembrane helices) is what a cell-surface protein would have. One caveat is kept explicit. Vertebrate OST-alpha needs OST-beta to reach the plasma membrane, and no fly OST-beta is known. So the location is a homology inference, not a measured fact. It is the most specific location the evidence supports, and no evidence points to another compartment. Supporting Evidence: file:DROME/CG6836/CG6836-uniprot.txt SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane file:DROME/CG6836/CG6836-bioinformatics/RESULTS.md In the NJ tree CG6836 is sister to the vertebrate SLC51A clade (human, mouse, zebrafish). PMID:20538072 It is important to note that the list of putative OSTΞ± orthologues includes genes from invertebrates such as the sea squirt (Ciona intestinalis; ENSCING00000009741), fruit fly (Drosophila melanogaster; FBgn0036834), and roundworm (Caenorhabditis elegans; C18A3.4). PMID:23506901 Heterodimerization of the two subunits increases the stability of the individual proteins, facilitates their post-translational modification, and is required for delivery of the functional transporter complex to the plasma membrane. |
| GO:0016020 membrane | IEA GO_REF:0000117 | ACCEPT | Summary: Integral membrane location is directly supported by the seven predicted transmembrane helices. Reason: This is an ARBA rule-based row, so the rule itself is not used as evidence. The claim stands on sequence features of the 328-residue canonical product. It has seven independently predicted helical transmembrane segments and an OST-alpha family classification. The broad term says only what the sequence directly shows. It is consistent with, and not in conflict with, the more specific plasma membrane row, which rests on ortholog inference. Supporting Evidence: file:DROME/CG6836/CG6836-uniprot.txt FT TRANSMEM 45..65 file:DROME/CG6836/CG6836-uniprot.txt Belongs to the OST-alpha family. {ECO:0000305}. |
| GO:0016020 membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Membrane location transferred from mouse Slc51a is sound and agrees with the sequence features. Reason: The donor, mouse Slc51a (Q8R000), is in the OST-alpha lineage that the re-review tree places CG6836 in, so this is a phylogenetically appropriate transfer. The curators transferred only a location from the donor. They did not transfer its bile-acid transport activity or its enterohepatic process terms. That omission is treated as deliberate, and those terms are not added here. Supporting Evidence: file:DROME/CG6836/CG6836-bioinformatics/RESULTS.md In the NJ tree CG6836 is sister to the vertebrate SLC51A clade (human, mouse, zebrafish). file:DROME/CG6836/CG6836-uniprot.txt FT TRANSMEM 45..65 |
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Download this section (compressed HTML)Q: Does CG6836 reach the plasma membrane on its own, or does it need a fly single-pass partner that plays the role of vertebrate OST-beta?
Q: Is CG6836 left out of the PANTHER 19.0 fly classification on purpose, and which PTHR23423 subfamily would its sequence score into?
Q: Are the substrates ecdysteroid conjugates or other steroid-derived solutes, the class proposed as the ancestral cargo of the OST-alpha lineage?
Experiment: Tag endogenous CG6836 by CRISPR knock-in. Determine its tissue distribution and apical or basolateral polarity in epithelia such as the midgut and Malpighian tubules. Use surface biotinylation and PNGase F to test the predicted extracellular glycosylated N-terminus.
Experiment: Express CG6836 in Xenopus oocytes, alone and together with candidate fly partners. Measure uptake and efflux of radiolabelled steroid conjugates (estrone-3-sulfate, taurocholate as a positive control set by the vertebrate transporter) and of ecdysteroid conjugates.
What is not known β curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: Whether CG6836 transports anything, which solute it moves, and whether it needs a partner subunit are unknown.
OPEN BIOLOGY WHOLLY_DARK
What is known: CG6836 is placed in the OST-alpha lineage, whose vertebrate members transport bile acids and steroid conjugates only as OST-alpha/OST-beta heterodimers. Flies have no recognized OST-beta, and insects lack bile acids.
What would resolve it: Heterologous expression (Xenopus oocytes or S2 cells), alone and with candidate fly single-pass partners, with uptake and efflux assays for steroid conjugates, ecdysteroids and eicosanoid-like lipids.
Provenance (the field's own admissions):
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