Disruption of zebrafish cyclin G-associated kinase (GAK) function impairs the expression of Notch-dependent genes during neurogenesis and causes defects in neuronal development.
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Zebrafish has two auxilin paralogs, GAK and auxilin (zAux), which differ in domain structure (GAK has an N-terminal kinase domain) and expression patterns. Both can functionally substitute for Drosophila auxilin in rescuing Notch signaling defects, and the J-domain is essential for this rescue.
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GFP-tagged zAux expressed in HeLa cells is mostly cytosolic at low expression levels with enrichment near perinuclear regions that overlap with clathrin, likely representing the trans-Golgi network.
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zAux expression during embryonic development is restricted to neural tissues: hindbrain neurons, spinal cord neurons, and otic vesicles.
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Electronic Gene Ontology annotations created by transferring manual GO annotations between related proteins based on shared sequence features
Electronic Gene Ontology annotations created by ARBA machine learning models
Deep research report for dnajc6 (A0A8M9QG43) in Danio rerio
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Auxilin/DNAJC6 is a J-domain protein co-chaperone that recruits and activates HSC70 to catalyze ATP-dependent disassembly of clathrin coats at the terminal step of clathrin-mediated endocytosis, essential for synaptic vesicle recycling.
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The PTEN-like domain binds phosphoinositides to target auxilin to endocytic membranes; the domain has only probable phosphatase activity and its primary role is membrane targeting.
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Loss-of-function mutations in DNAJC6 cause PARK19 (autosomal recessive juvenile-onset Parkinson's disease), linking auxilin dysfunction to dopaminergic neurodegeneration via accumulation of clathrin-coated vesicles and impaired synaptic vesicle recycling.