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
Human Costars Family Protein ABRACL Modulates Actin Dynamics and Cell Migration and Associates with Tumorigenic Growth.
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Purified untagged recombinant ABRACL binds F-actin directly in a co-sedimentation assay, though weakly.
"These results indicated that purified recombinant ABRACL bound to F-actin, although very weakly, under the in vitro experimental conditions."
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ABRACL and cofilin interact in cells, shown by proximity ligation that is lost on knockdown of either partner and by co-immunoprecipitation of endogenous cofilin.
"Fluorescence PLA signals were detected in the control cells but greatly diminished in ABRACL- or cofilin-knockdown cells"
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ABRACL inhibits cofilin-stimulated depolymerisation of pyrene F-actin in a dose-dependent manner.
"the addition of ABRACL in the reaction blunted this effect of cofilin in a dose-dependent manner"
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The inhibition is not simple displacement - ABRACL does not prevent cofilin from binding F-actin.
"We found that ABRACL did not inhibit the co-sedimentation of cofilin with F-actin"
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ABRACL alone inhibits actin polymerisation in vitro, which the authors note is inconsistent with the direction of the cellular F/G-actin phenotype.
"These in vitro results appeared to contradict the above-mentioned finding of decreased F/G-actin ratios in cells lacking ABRACL"
Costars, a Dictyostelium protein similar to the C-terminal domain of STARS, regulates the actin cytoskeleton and motility.
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cosA-null Dictyostelium cells move more slowly toward cAMP but steer normally, indicating a motility-machinery defect rather than a chemotactic-orientation defect.
"Analysis of cell motion in cAMP gradients revealed decreased speed but wild-type-like directional persistence of cosA(-) cells, suggesting a defect in the cellular machinery for motility rather than for chemotactic orientation."
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Loss of Costars increases cytoskeleton-associated actin, the opposite sign to the human knockdown phenotype.
"cosA(-) cells exhibited changes in the actin cytoskeleton, showing aberrant distribution of F-actin in fluorescence cell staining and an increased amount of cytoskeleton-associated actin."
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The human ortholog functionally replaces Costars in Dictyostelium, which is the strongest available warrant for the phylogenetic transfer.
"Expressing cosA or its human counterpart mCostars eliminated abnormalities of cosA(-) cells."
Characterization of the Abracl-Expressing Cell Populations in the Embryonic Mammalian Telencephalon.
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The paper's only statement linking Abracl to cilia is a citation of a third-party high-throughput proteomics study, not an observation of its own.
"a high-throughput proteomics study in non-neuronal cell lines has shown that Abracl is associated with the primary cilia"
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Its own data place Abracl outside the ventricular zone, where the ciliated progenitors reside.
"our results show that neither Abracl mRNA nor Abracl were expressed in the VZ"
A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface.
Solution structure of the human HSPC280 protein.
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The fold is winged helix-like but the protein does not bind DNA, which forecloses the annotation a winged-helix fold would otherwise invite.
"However, HEPC280 is not a typical DNA-binding winged helix protein in that it lacks DNA-binding activity."
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A hydrophobic groove is conserved between the Costars family and the Abra C-terminal domain and is proposed to mediate protein interaction.
"Comparisons with the C-terminal 80-residue domain of proteins in the Abra family reveal a conserved hydrophobic groove in the HSPC280 family, which may allow HSPC280 to interact with other proteins."
HSPC280, a winged helix protein expressed in the subventricular zone of the developing ganglionic eminences, inhibits neuronal differentiation.
What actually places ABRACL in the cilium?
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The entire physical-interaction record for ABRACL in IntAct is one proximity-labelling experiment.
"Detection methods observed: proximity-dependent biotin identification."
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The Costars family is retained in four proteomes that build no cilium, while four cilium-core control families are absent from all of them.
"Costars distribution therefore does not track cilium presence in either direction."
Affinage mechanistic annotation for ABRACL (human)