Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Combined Automated Annotation using Multiple IEA Methods
Defective calmodulin-dependent rapid apical endocytosis in zebrafish sensory hair cell mutants.
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The study interprets rapid FM1-43 uptake as apical endocytosis; later channel-permeation evidence makes the specificity of that interpretation uncertain for mercury.
"rapid apical endocytosis in zebrafish lateral line sensory hair cells is calcium and calmodulin dependent"
Integration of Tmc1/2 into the mechanotransduction complex in zebrafish hair cells is regulated by Transmembrane O-methyltransferase (Tomt).
Genetic analysis of vertebrate sensory hair cell mechanosensation: the zebrafish circler mutants.
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The mercury mutant class has impaired acoustic-vibrational responses and reduced microphonics, supporting a mechanotransduction defect.
"orbiter, mercury, and gemini larvae have normal hair cell morphology and yet do not respond to acoustic-vibrational stimuli"
UniProtKB entry A0A193KX02 for Danio rerio tomt
Falcon deep research for Danio rerio tomt (UniProt A0A193KX02)
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Falcon deep research synthesizes the Erickson 2017 eLife study and the Jung & Muller 2023 review to conclude that
zebrafish Tomt is a Golgi/ER secretory-pathway protein essential for hair-cell mechano-electrical transduction, where
it selectively enables trafficking and bundle targeting of the Tmc1/Tmc2 MET channel subunits rather than acting as a
bundle-resident structural channel component.
"functions primarily in the **secretory pathway (Golgi/ER)** to enable **trafficking and bundle targeting of Tmc1/Tmc2 (MET channel subunits)**"
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Falcon supports a trafficking-facilitator model, with the primary physical-interaction experiment performed using mouse TOMT and TMC1 in HEK cells; direct zebrafish chaperone biochemistry remains unestablished.
"support a direct physical interaction between **TOMT and TMC1**, consistent with a model where TOMT acts as a chaperone/escort or trafficking facilitator in the secretory pathway"
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Falcon summarizes dispensability of canonical COMT chemistry for MET; the H183A rescue is mouse TOMT in zebrafish, and does not show lack of native zebrafish methyltransferase activity.
"key data suggest canonical catechol-O-methyltransferase chemistry is **not strictly required** for its MET role"
Actual PTHR43836 PAINT lineage and positive ancestral assertions for zebrafish Tomt
FM1-43 dye behaves as a permeant blocker of the hair-cell mechanotransducer channel.
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Primary mouse cochlear experiments establish an alternative explanation for rapid FM1-43 hair-cell loading, distinct from vesicle uptake.
"FM1-43 behaves as a permeant blocker of the mechanotransducer channel."