InterPro domain: IPR035984

Acyl-CoA-binding protein (ACBP) is a small (10 Kd) protein that binds medium- and long-chain acyl-CoA esters with very high affinity and may function as an intracellular carrier of acyl-CoA esters [ 1 ]. ACBP is also known as diazepam binding inhibitor (DBI) or endozepine (EP) because of its ability 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 [ 2 ].

ACBP is a highly conserved protein of about 90 residues that is found in all four eukaryotic kingdoms, Animalia, Plantae, Fungi and Protista, and in some eubacterial species [ 3 ].

Although ACBP occurs as a completely independent protein, intact ACB domains have been identified in a number of large, multifunctional proteins in a variety of eukaryotic species. These include large membrane-associated proteins with N-terminal ACB domains, multifunctional enzymes with both ACB and peroxisomal enoyl-CoA Delta(3), Delta(2)-enoyl-CoA isomerase domains, and proteins with both an ACB domain and ankyrin repeats ( IPR002110 ) [ 4 ].

The ACB domain consists of four alpha-helices arranged in a bowl shape with ahighly exposed acyl-CoA-binding site. The ligand is boundthrough specific interactions with residues on the protein, most notablyseveral conserved positive charges that interact with the phosphate group onthe adenosine-3'phosphate moiety, and the acyl chain is sandwiched between thehydrophobic surfaces of CoA and the protein [ 4 ].

Other proteins containing an ACB domain include:

• Endozepine-like peptide (ELP) (gene DBIL5) from mouse [ 5 ]. ELP is a testis-specific ACBP homologue that may be involved in the energy metabolism of the mature sperm.
• MA-DBI, a transmembrane protein of unknown function which has been found in mammals. MA-DBI contains a N-terminal ACB domain.
• DRS-1 [ 6 ], a human protein of unknown function that contains a N-terminal ACB domain and a C-terminal enoyl-CoA isomerase/hydratase domain.

1. Molecular cloning of the gene for the yeast homolog (ACB) of diazepam binding inhibitor/endozepine/acyl-CoA-binding protein. Proc. Natl. Acad. Sci. U.S.A. 89, 11287-91
2. Diazepam binding inhibitor (DBI): a peptide with multiple biological actions. Life Sci. 49, 325-44
3. Evolution of the acyl-CoA binding protein (ACBP). Biochem. J. 392, 299-307
4. Binding site differences revealed by crystal structures of Plasmodium falciparum and bovine acyl-CoA binding protein. J. Mol. Biol. 309, 181-92
5. A novel endozepine-like peptide (ELP) is exclusively expressed in male germ cells. Mol. Cell. Endocrinol. 122, 69-80
6. Molecular cloning and expression of a novel human cDNA related to the diazepam binding inhibitor. Biochim. Biophys. Acta 1454, 126-31