Gene Ontology annotation through association of InterPro records with GO terms
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
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
The novel gene encoding a putative transmembrane protein is mutated in gnathodiaphyseal dysplasia (GDD).
Expression and function of epithelial anoctamins.
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The expression survey found surface localization but no ANO5 calcium-activated halide response in its FRT assay.
"When expressed in
Fisher Rat Thyroid (FTR) cells, all ANO proteins localized to the plasma
membrane but only ANO1, 2, 6, and 7 produced Ca(2+)-activated Cl(-) conductance,
as analyzed by ATP-induced iodide quenching of YFP fluorescence."
ANOs 3-7 in the anoctamin/Tmem16 Cl- channel family are intracellular proteins.
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ANO3–7 expression did not produce calcium-activated chloride currents in the tested HEK293 context; intracellular retention limits a conclusion about intrinsic channel capacity.
"Expression of ANOs 3-7 in
HEK293 cells did not generate Cl(-) currents activated by intracellular Ca(2+),
as determined by whole cell patch clamp electrophysiology."
Anoctamins are a family of Ca2+-activated Cl- channels.
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The family expression study reports transient calcium-activated currents, including the ANO5 experiment; it did not measure ANO5-specific anion ranking.
"Using whole-cell patch clamping we
demonstrate that Ano4-10 are all able to produce transient Ca(2+)-activated
Cl(-) currents when expressed in HEK293 cells."
ANO5 ensures trafficking of annexins in wounded myofibers.
ANOs transport cytosolic Cl- to extracellular region
ANO5, ANO6 expose PS, PE on endothelial cells
Gain of function of TMEM16E/ANO5 scrambling activity caused by a mutation associated with gnathodiaphyseal dysplasia.
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Human ANO5 expression produces currents under conditions where matched controls show only small background currents.
"Under identical experimental conditions, non-transfected control cells presented only small background currents lacking any time dependence"
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Calcium favors activation of ANO5-associated currents but is not an absolute requirement in the tested CHO expression system.
"the presence of cytosolic Ca2+ was not strictly necessary for TMEM16E activation, but strongly favored it"
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Calcium-stimulated ANO5 expression supports surface phosphatidylserine exposure in cell assays.
"we observed clear fluorescence signals lining the cell boundaries of EGFP-positive cells after 5–10 min, but not of non-transfected neighboring cells"
Anoctamin 5/TMEM16E facilitates muscle precursor cell fusion.
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Exogenous human ANO5 supports calcium-induced phosphatidylserine exposure in HEK293 cells.
"Ca2+ stimulation elicited PtdSer exposure in the vast majority of cells expressing exogenous ANO5 in contrast to parental HEK293 cells"
Dysregulated calcium homeostasis prevents plasma membrane repair in Anoctamin 5/TMEM16E-deficient patient muscle cells.
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ANO5-GFP overlaps the ER marker in human myoblasts.
"co-expression of ANO5-GFP with an RFP-tagged ER luminal marker (RFP-KDEL or ER-RFP) in healthy human myoblasts showed overlapping reticular staining of both proteins"
TMEM16E regulates endothelial cell procoagulant activity and thrombosis.
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Endogenous endothelial TMEM16E contributes to phosphatidylserine exposure in human HUVECs.
"PS externalization in response to TNF-α or Ca2+ ionophore was markedly inhibited in HUVECs following silencing of TMEM16E or TMEM16F"
A novel missense mutation in ANO5/TMEM16E is causative for gnathodiaphyseal dyplasia in a large Italian pedigree.
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The GDD study provides contrary evidence to a general calcium-activated chloride-channel interpretation.
"However, recent data together with our own experiments reported here add weight
to the hypothesis that ANO5 may not function as calcium-activated chloride
channel."
TMEM16E/ANO5 mutations related to bone dysplasia or muscular dystrophy cause opposite effects on lipid scrambling.
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The tested muscle-disease and GDD variants have opposing effects on ANO5 activity in the same HEK293 assay system; only abstract-level details were available.
"Our results collectively
demonstrate that, on the level of protein function, MD mutations are associated
to loss-of-function and GDD mutations to gain-of-function phenotypes, confirming
conjectures made on the basis of inheritance modes."
Molecular cloning and characterization of the murine gnathodiaphyseal dysplasia gene GDD1.
Functional Interdependence of Anoctamins May Influence Conclusions from Overexpression Studies.
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ANO5-associated current depends on expression background; the Discussion links it to ANO6 absence rather than ANO6 presence.
"ion currents attributed to the expression of ANO5, ANO9, or ANO10 were dependent on the presence (ANO9) or absence (ANO5 and -10) of ANO6"
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Endogenous ANO6 adds to the total scrambling signal alongside ANO5-associated activity.
"Overall, endogenous ANO6 provides a small scramblase activity in addition to the PL scramblase induced by ANO3 and ANO5, but not by ANO9"
Targeting of Intracellular TMEM16 Proteins to the Plasma Membrane and Activation by Purinergic Signaling.
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Engineered CFP-CAAX surface targeting does not yield detectable added ANO5 scrambling in this assay; this negative result must be distinguished from non-CAAX experiments.
"In our study, we could not confirm scrambling activity for TMEM16E, TMEM16J and TMEM16K"