GIPC3 is a broadly expressed, 312-residue member of the GIPC family, with a central PDZ domain and flanking GH1 and GH2 regions. Recessive variants cause nonsyndromic sensorineural hearing loss. Mouse orthology supports a MYO6-binding role, while the human hair-cell mechanism remains incompletely characterized.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Positive ST6GAL2 binding lacks a specific functional assignment. Reason: The positive ST6GAL2 pair is preserved with Q96JF0-2. Partner enzyme activity does not establish a specific GIPC3 function; remove the uninformative generic label. Clone limits are documented in the manual page. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Positive PLEKHA2 binding lacks a specific functional assignment. Reason: A8K727 resolves to PLEKHA2/Q9HB19. Its phosphoinositide-binding role does not establish a GIPC3 adaptor mechanism. The positive pair remains documented despite removal of the uninformative label. |
| GO:0070853 myosin VI binding | ISO PMID:37096733 GIPC3 couples to MYO6 and PDZ domain proteins, and shapes th... | NEW | Summary: Propose conditional MYO6-binding transfer from mouse. Reason: Mouse binding plus verified orthology supports conditional ISO. Curate donor Q8R5M0 IPI from PMID:37096733 before implementation; current ND-only annotations do not establish that prerequisite. This is a proposed curation ordering, not a failed hard validation rule. Propagation Review Root cause: SOURCE STALE OR MISSING Sources checked: UniProtKB:Q8R5M0 · Gipc3 SOURCE STALE OR MISSING The experimental literature supports donor binding and official orthology supports transfer, but the retained QuickGO donor record lacks this term. This flags a missing annotation prerequisite, not stale biology, donor misidentification or evidence of functional loss. Supporting Evidence: PMID:37096733 GH2 domain of GIPC3 interacts with HCBD of MYO6 UniProtKB:Q8R5M0 file:human/GIPC3/GIPC3-deep-research-manual.md |
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Download this section (compressed HTML)Q: Can mouse Q8R5M0 be curated to GO:0070853 with IPI from PMID:37096733 before implementing the proposed human ISO annotation?
Experiment: Compare purified human GIPC3 binding to MYO6 and MYO18A individually and together. In a hair-cell model, test interaction-defective mutants with matched expression/localization for rescue of apical geometry.
Type: Binding, ternary-complex reconstitution and controlled rescue
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The molecular mechanism by which human GIPC3 supports hair-cell organization is unresolved, including whether it forms a force-transmitting MYO6–MYO18A bridge.
OPEN BIOLOGY MF_DARK
What is known: Mouse experiments establish partner binding and apical organization; the corresponding human interaction is inferred by orthology. MYO6 may act as a motor or anchor, but simultaneous force coupling and human apical localization remain untested.
What would resolve it: Test human partner binding and simultaneous complex formation, then separate structural coupling from protein abundance in hair cells.
Provenance (the field's own admissions):
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