ANKRD46 (ankyrin repeat domain-containing 46) is a small uncharacterized protein of 228 residues, with four N-terminal ankyrin repeats and a single predicted C-terminal transmembrane helix, and endogenously tagged ANKRD46 localizes prominently to the endoplasmic reticulum, consistent with a tail-anchored ER membrane protein. It is a validated target of miR-21, whose inhibition raises ANKRD46 levels. No molecular activity or biological role has been established.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0016020 membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Membrane (IEA, UniProt subcellular location). ANKRD46 has a single predicted C-terminal transmembrane helix, and OpenCell places endogenously tagged ANKRD46 prominently in the endoplasmic reticulum; accepted, with the ER added as a NEW, more specific row. Reason: UniProt annotates [file:human/ANKRD46/ANKRD46-uniprot.txt "FT TRANSMEM 190..210"] and states [file:human/ANKRD46/ANKRD46-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass membrane"] (ECO:0000305, curator inference). OpenCell imaging supports a membrane location: [file:human/ANKRD46/ANKRD46-bioinformatics/RESULTS.md "ANKRD46 cell_line_id=1394 terminus=N categories=['publication_ready', 'er_3', 'vesicles_1']"] Supporting Evidence: file:human/ANKRD46/ANKRD46-uniprot.txt FT TRANSMEM 190..210 file:human/ANKRD46/ANKRD46-uniprot.txt CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass membrane file:human/ANKRD46/ANKRD46-bioinformatics/RESULTS.md ANKRD46 cell_line_id=1394 terminus=N categories=['publication_ready', 'er_3', 'vesicles_1'] |
| GO:0005783 endoplasmic reticulum | HDA PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | NEW | Summary: Endoplasmic reticulum (NEW, HDA). In OpenCell, endogenously N-terminally tagged ANKRD46 in HEK293T cells gives a prominent ER signal, with only a weak vesicle signal. Reason: OpenCell records [file:human/ANKRD46/ANKRD46-bioinformatics/RESULTS.md "ANKRD46 cell_line_id=1394 terminus=N categories=['publication_ready', 'er_3', 'vesicles_1']"], where [file:human/ANKRD46/ANKRD46-bioinformatics/RESULTS.md "grade 3 = Prominent signal"] This is a high-throughput imaging survey, hence HDA. It fits the predicted C-terminal transmembrane helix [file:human/ANKRD46/ANKRD46-uniprot.txt "FT TRANSMEM 190..210"], the usual signature of an ER-inserted tail-anchored protein. GO:0005783 is a more specific location than the existing membrane row, but not its descendant (membrane is not an ancestor of the ER organelle term), so it is not redundant. Supporting Evidence: file:human/ANKRD46/ANKRD46-bioinformatics/RESULTS.md ANKRD46 cell_line_id=1394 terminus=N categories=['publication_ready', 'er_3', 'vesicles_1'] file:human/ANKRD46/ANKRD46-bioinformatics/RESULTS.md grade 3 = Prominent signal file:human/ANKRD46/ANKRD46-uniprot.txt FT TRANSMEM 190..210 |
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Download this section (compressed HTML)Q: Is ANKRD46 inserted into the ER as a tail-anchored protein with its ankyrin repeats facing the cytosol, and which of its many deposited membrane-protein interactors are genuine?
Experiment: Image endogenously tagged ANKRD46 against organelle markers and test protease protection of its N-terminal ankyrin domain to establish topology.
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: ANKRD46's molecular activity and biological role are unknown; it is an ER membrane protein by high-throughput imaging, and none of its many deposited interactors has been validated.
OPEN BIOLOGY MF_DARK
What is known: The only GOA annotation is membrane, inferred from a predicted transmembrane helix; OpenCell imaging adds the ER. Interaction databases hold many high-throughput partners (121 in IntAct, 138 in BioGRID), most of them membrane proteins from two-hybrid screens, but none is validated or captured in a GO row. The literature treats ANKRD46 only as a miRNA target. PAN-GO assigns nothing.
Significance: ANKRD46 is a recurrent miR-21 target in cancer studies, but without a known function its regulation cannot be interpreted.
What would resolve it: Confirm the ER localization against ER markers, test its topology as a tail-anchored protein, and validate the strongest deposited interactors.
Provenance (the field's own admissions):
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