Gene or accession: CG8627 Missed gene Comments: Dear FlyBase Curators, Correct annotation would be: acyl-coa binding protein \- binds Acyl-CoA \- acts as a transporter and/or pool-former of Acyl-CoA Synonyms (aliases) for DBI: \- diazepam-binding protein (DBI) \- acyl-CoA binding protein (ACBP) \- endozepine _________________________________ 1. Many possible biological roles have been suggested for DBI \- binding of Acyl-CoA \- stimulation of steroidogenesis through peripheral benzodiazepine receptors (also known as mitochondrial benzodiazepine receptors) \- modulation of GABA receptor type A (DBI/ACBP protein was first purified and also named on the bases of its ability to inhibit diazepam binding to GABA receptors of type A) \- stimulation of insulin secretion \- antibacterial properties \- stimulation of cholecystokinin (CCK) secretion \- binding of lead (lead-binding protein) 2. However the binding of Acyl-CoA is the only function of DBI/ACBP which has been supported with remarkable body of experimental evidence. 3. Evidence: \- extensive biochemical data \- for a reviews: Kragelund BB et al. Biochim Biophys Acta. 1999 Nov 23;1441(2-3):150-61. Review. Knudsen J et. al. Mol Cell Biochem. 1999 Feb;192(1-2):95-103. Review. \- three-dimensional structure of ACBP/DBI and palmitoyl-CoA has been resolved by multidimensional nuclear magnetic resonance (NMR) spectroscopy Kragelund BB, et al. J Mol Biol. 1993 Apr 20;230(4):1260-77. \- knock-out experiments in S. cerevisiae Schjerling CK et. al. J Biol Chem. 1996 Sep 13;271(37):22514-21. \- please note that DBI/ACBP has been conserved throughout the evolution and is found in unicellular eukaryote S. cerevisiae and also in prokaryote Deinococcus radiodurans. Therefore it is highly unlikely that the real function of ACBP/DBI would be binding of diazepam..... 4. Our own studies have shown that in D. melanogaster the expression of ACBP/DBI is expressed in the following tissues: \- outer vacuolate epithelium of the stomodeal valve of the cardia \- in distal part of the anterior Malpighian tubules, \- fat body, \- gametes of both sexes \- pupal and larval brains (no expression in adult CNS). Localization and morphological characteristics of structures that do express DBI/ACBP suggest that these structures are most likely glial cells and their processes. Kolmer M, et. al. Mol Cell Biol. 1994 Oct;14(10):6983-95. 5. On the basis of the expression of DBI in some but not all tissues with high energy consumption, we proposed that in D. melanogaster, DBI is involved in energy metabolism in a manner that depends on the substrate used for energy production (most likely Acyl-CoA, however we have no direct experimental evidence so far). _________________________________________________ Finally, please also see a Swiss-Prot annotation line below (entry name: ACBP_BOVIN) FUNCTION: BINDS MEDIUM- AND LONG-CHAIN ACYL-COA ESTERS WITH VERY HIGH AFFINITY AND MAY FUNCTION AS AN INTRACELLULAR CARRIER OF ACYL-COA ESTERS. IT IS ALSO ABLE TO DISPLACE DIAZEPAM FROM THE BENZODIAZEPINE (BZD) RECOGNITION SITE LOCATED ON THE GABA TYPE A RECEPTOR. IT IS THEREFORE POSSIBLE THAT THIS PROTEIN ALSO ACTS AS A NEUROPEPTIDE TO MODULATE THE ACTION OF THE GABA RECEPTOR. _______________________________ Thank you for your time and for keeping FlyBase up and running. with all the best wishes, Meelis