4it6
Crystal structure of amino acid residues 1-120 of CG17282
Structural highlights
FunctionBDBT_DROME Functions in planar polarity establishment and circadian rhythms by promoting the activity and localization of dco/dbt (PubMed:24210908, PubMed:26082158, PubMed:36994075). Required for regulating the levels of dco/dbt and per in the nuclei of photoreceptor cells and thereby is involved in normal oscillations of the circadian clock proteins in the eye (PubMed:24210908, PubMed:36994075). In the dark, the cry circadian and rhodopsin visual pathways, activate the accumulation of the protein into Arr1- and Arr2-dependent cytosolic foci which are required for dco localization to photoreceptor nuclei (PubMed:24210908, PubMed:26082158, PubMed:36994075). It is possible that the accumulation into foci results in the dissociation of the protein from dco, thus allowing dco to interact with importins and microtubles for nuclear transport (PubMed:24210908, PubMed:26082158, PubMed:36994075). By promoting nuclei localization and kinase activity of dco towards per, it is essential for regulating normal cycles of per nuclear accumulation in brain circadian neurons and thus is important for normal circadian behavior (PubMed:24210908, PubMed:36994075). Essential for regulating the establishment of planar cell polarity in the wing (PubMed:32750048). Forms a complex with Ankrd49 which likely functions in the regulation of planar polarity by promoting the activity of dco during planar polarity establishment (PubMed:32750048). Within the complex, directly promotes dco activity in regulating phosphorylation and asymmetric localization of core planar polarity proteins such as dsh (PubMed:32750048).[1] [2] [3] [4] Publication Abstract from PubMedThe kinase DOUBLETIME is a master regulator of the Drosophila circadian clock, yet the mechanisms regulating its activity remain unclear. A proteomic analysis of DOUBLETIME interactors led to the identification of an unstudied protein designated CG17282. RNAi-mediated knockdown of CG17282 produced behavioral arrhythmicity and long periods and high levels of hypophosphorylated nuclear PERIOD and phosphorylated DOUBLETIME. Overexpression of DOUBLETIME in flies suppresses these phenotypes and overexpression of CG17282 in S2 cells enhances DOUBLETIME-dependent PERIOD degradation, indicating that CG17282 stimulates DOUBLETIME's circadian function. In photoreceptors, CG17282 accumulates rhythmically in PERIOD- and DOUBLETIME-dependent cytosolic foci. Finally, structural analyses demonstrated CG17282 is a noncanonical FK506-binding protein with an inactive peptide prolyl-isomerase domain that binds DOUBLETIME and tetratricopeptide repeats that may promote assembly of larger protein complexes. We have named CG17282 BRIDE OF DOUBLETIME and established it as a mediator of DOUBLETIME's effects on PERIOD, most likely in cytosolic foci that regulate PERIOD nuclear accumulation. Noncanonical FK506-Binding Protein BDBT Binds DBT to Enhance Its Circadian Function and Forms Foci at Night.,Fan JY, Agyekum B, Venkatesan A, Hall DR, Keightley A, Bjes ES, Bouyain S, Price JL Neuron. 2013 Nov 20;80(4):984-96. doi: 10.1016/j.neuron.2013.08.004. Epub 2013, Nov 7. PMID:24210908[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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