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Gene Review

ACBD5  -  acyl-CoA binding domain containing 5

Bos taurus

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Disease relevance of DBI

  • A fraction highly enriched for recombinant ACBP was obtained by extracting induced E. coli cells with 1 M-acetic acid [1].
  • The photocrosslinked acyl-CoA-ACBP complex was separated from unlabelled ACBP on reverse-phase h.p.l.c. and the purified complex was digested with trypsin, Staphylococcus aureus V8 proteinase or endoproteinase Asp-N [2].

High impact information on DBI

  • The folding kinetics of bovine acyl-CoA binding protein was studied by (15)N relaxation dispersion measurements under equilibrium conditions [3].
  • The formation of a native-like structure containing eight conserved hydrophobic residues is rate limiting in two-state protein folding of ACBP [4].
  • Frog DBI contains two paired basic amino acids (Lys-Lys) at positions 14-15 and 62-63 and a single cysteine within the biologically active region of the molecule [5].
  • The distribution of both DBI mRNA and DBI-like immunoreactivity indicates that DBI is selectively expressed in glial cells [5].
  • Endozepine competes with benzodiazepines for saturable binding sites in synaptosomes and in mitochondria of specific peripheral tissues [6].

Biological context of DBI


Anatomical context of DBI

  • Our microscopic results point to the role of ACBP as an intermembrane transporter of acyl-CoA and demonstrate the ability of AFM to reveal the remodelling of membranes by surfactants and proteins [10].
  • The regional distribution of DBI in the human brain is similar to that observed in rat brain: high concentrations in cortical and limbic areas, cerebellum, and brainstem, and low concentrations in the basal ganglia [11].
  • Measurements of CA activity in intact red blood cells were conducted to confirm DBI remains extracellular [12].
  • Moreover, the biosynthesis of DBI is up-regulated in the cerebellum and cerebral cortex of rats made tolerant to diazepam, suggesting that changes in the biosynthesis of DBI might be one of the mechanisms eliciting tolerance to benzodiazepine [13].
  • Data presented here suggest that (i) Ep/DBI levels are not regulated by trophic hormones in these steroidogenic cell lines, and (ii) that the peptide has a relatively long half-life (greater than 3 h), a finding incompatible with suggestions of it having a rapid turnover [14].

Associations of DBI with chemical compounds

  • Both endozepine and DBI have been shown to elicit behavioral effects, suggesting that they function as pharmacologically-active ligands of the GABA (gamma-aminobutyric acid) receptor complex [15].
  • Human endozepine, an 86 amino acid polypeptide, was originally isolated from human brain tissue as a putative ligand of the benzodiazepine receptor [15].
  • Inhibition of total CA activity with acetazolamide and inhibition of extracellular-facing membrane-associated CA with DBI caused an identical intracellular pH decrease in intact NPE cells [12].
  • Diazepam binding inhibitor (DBI) is a peptide, initially identified for its ability of displacing the binding of diazepam [13].
  • We have used two cell lines (Y-1 mouse adrenal cell tumour and MA-10 mouse Leydig cell tumour), both of which exhibit hormone stimulated steroid production, to investigate the role of Ep/DBI in acute hormone stimulated steroidogenesis [14].

Other interactions of DBI


Analytical, diagnostic and therapeutic context of DBI


  1. Gene synthesis, expression in Escherichia coli, purification and characterization of the recombinant bovine acyl-CoA-binding protein. Mandrup, S., Højrup, P., Kristiansen, K., Knudsen, J. Biochem. J. (1991) [Pubmed]
  2. Determination by photoaffinity labelling of the hydrophobic part of the binding site for acyl-CoA esters on acyl-CoA-binding protein from bovine liver. Hach, M., Pedersen, S.N., Börchers, T., Højrup, P., Knudsen, J. Biochem. J. (1990) [Pubmed]
  3. The inverted chevron plot measured by NMR relaxation reveals a native-like unfolding intermediate in acyl-CoA binding protein. Teilum, K., Poulsen, F.M., Akke, M. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  4. The formation of a native-like structure containing eight conserved hydrophobic residues is rate limiting in two-state protein folding of ACBP. Kragelund, B.B., Osmark, P., Neergaard, T.B., Schiødt, J., Kristiansen, K., Knudsen, J., Poulsen, F.M. Nat. Struct. Biol. (1999) [Pubmed]
  5. Frog diazepam-binding inhibitor: peptide sequence, cDNA cloning, and expression in the brain. Lihrmann, I., Plaquevent, J.C., Tostivint, H., Raijmakers, R., Tonon, M.C., Conlon, J.M., Vaudry, H. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  6. Identification of des-(Gly-Ile)-endozepine as an effector of corticotropin-dependent adrenal steroidogenesis: stimulation of cholesterol delivery is mediated by the peripheral benzodiazepine receptor. Besman, M.J., Yanagibashi, K., Lee, T.D., Kawamura, M., Hall, P.F., Shively, J.E. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  7. Complete amino acid sequences of bovine and human endozepines. Homology with rat diazepam binding inhibitor. Marquardt, H., Todaro, G.J., Shoyab, M. J. Biol. Chem. (1986) [Pubmed]
  8. Short-range, long-range and transition state interactions in the denatured state of ACBP from residual dipolar couplings. Fieber, W., Kristjansdottir, S., Poulsen, F.M. J. Mol. Biol. (2004) [Pubmed]
  9. Bovine and human cDNA sequences encoding a putative benzodiazepine receptor ligand. Webb, N.R., Rose, T.M., Malik, N., Marquardt, H., Shoyab, M., Todaro, G.J., Lee, D.C. DNA (1987) [Pubmed]
  10. Acyl-coenzyme A organizes laterally in membranes and is recognized specifically by acyl-coenzyme A binding protein. Cohen Simonsen, A., Bernchou Jensen, U., Faergeman, N.J., Knudsen, J., Mouritsen, O.G. FEBS Lett. (2003) [Pubmed]
  11. Distribution of a putative endogenous modulator of the GABAergic system in human brain. Ferrarese, C., Appollonio, I., Frigo, M., Piolti, R., Tamma, F., Frattola, L. Neurology (1989) [Pubmed]
  12. Membrane-associated carbonic anhydrase in cultured rabbit nonpigmented ciliary epithelium. Wu, Q., Delamere, N.A., Pierce, W. Invest. Ophthalmol. Vis. Sci. (1997) [Pubmed]
  13. Diazepam binding inhibitor peptide: cloning and gene expression. Mocchetti, I., Santi, M.R. Neuropharmacology (1991) [Pubmed]
  14. Endozepine/diazepam binding inhibitor in adrenocortical and Leydig cell lines: absence of hormonal regulation. Brown, A.S., Hall, P.F., Shoyab, M., Papadopoulos, V. Mol. Cell. Endocrinol. (1992) [Pubmed]
  15. Human DBI (endozepine): relationship to a homologous membrane associated protein (MA-DBI). Todaro, G.J., Rose, T.M., Shoyab, M. Neuropharmacology (1991) [Pubmed]
  16. Stimulation by endozepine of the side-chain cleavage of cholesterol in a reconstituted enzyme system. Brown, A.S., Hall, P.F. Biochem. Biophys. Res. Commun. (1991) [Pubmed]
  17. Purification and characterization of variants of acyl-CoA-binding protein in the bovine liver. Jensen, M.S., Højrup, P., Rasmussen, J.T., Knudsen, J. Biochem. J. (1992) [Pubmed]
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