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Tbio Acyl-CoA-binding protein

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.

This gene encodes diazepam binding inhibitor, a protein that is regulated by hormones and is involved in lipid metabolism and the displacement of beta-carbolines and benzodiazepines, which modulate signal transduction at type A gamma-aminobutyric acid receptors located in brain synapses. The protein is conserved from yeast to mammals, with the most highly conserved domain consisting of seven contiguous residues that constitute the hydrophobic binding site for medium- and long-chain acyl-Coenzyme A esters. Diazepam binding inhibitor is also known to mediate the feedback regulation of pancreatic secretion and the postprandial release of cholecystokinin, in addition to its role as a mediator in corticotropin-dependent adrenal steroidogenesis. Three pseudogenes located on chromosomes 6, 8 and 16 have been identified. Multiple transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

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Property Summary

NCBI Gene PubMed Count 60
PubMed Score 242.76
PubTator Score 240.58

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (3)

Disease Target Count Z-score Confidence
Hepatic encephalopathy 25 3.353 1.7
Cryptosporidiosis 12 3.248 1.6

Expression

  Differential Expression (9)

Disease log2 FC p
chronic lymphosyte leukemia 1.300 1.9e-06
Multiple myeloma 2.267 1.5e-03
oligodendroglioma 1.600 3.0e-02
astrocytoma 1.300 9.6e-20
glioblastoma multiforme 1.300 9.1e-20
pancreatic ductal adenocarcinoma liver m... -2.305 1.3e-03
pediatric high grade glioma 1.300 1.1e-06
ovarian cancer 2.600 1.5e-06
pituitary cancer 1.800 1.2e-04

Synonym

Accession P07108 B8ZWD2 B8ZWD6 B8ZWD7 P08869 Q4VWZ6 Q53SQ7 Q6IB48 Q9UCI8 ACBP
Symbols EP
ACBP
ACBD1
CCK-RP

Gene

DBI

PANTHER Protein Class (1)

PDB

2CB8   2FJ9  

  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG Inparanoid

 UniProt Keyword (13)

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 GO Function (4)

 GO Component (4)

 GO Process (2)

 Compartment GO Term (28)

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 MGI Phenotype (8)

 HCA RNA Cell Line (56)

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Pathway (16)

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Gene RIF (26)

PMID Text
26290636 Serum endozepine-4 levels are increased in hepatic coma.
25898985 Structural and functional properties of ACBD1, commonly known as ACBP. [Review]
24819876 High ACBP expression is associated with non-small cell lung cancer.
24818357 There was a significant difference in the rs2276596 polymorphism C/A allele frequency of the DBI gene (P < 0.0001) between alcoholics and healthy controls.
24401326 results indicate that a dysfunction of the neurosteroid system might be operative in BPD in spite of unchanged DBI plasma levels.
24080521 Acyl-CoA binding protein and epidermal barrier function. [review]
23727119 Endogenous potentiation of GABAergic synaptic transmission and responses to GABA uncaging in the thalamic reticular nucleus is absent in mice in which DBI is deleted and mice in which benzodiazepine binding to alpha3 subunit-containing GABAARs is disrupted.
21448843 A human preadipocyte cell line SGBS is well suited to examine differential expression of the Acyl-CoA binding protein (ACBP) during adipogenesis.
20511713 Gene annotation enrichment analysis revealed ACBP-mediated down-regulation of 18 genes encoding key enzymes in glycerolipid, cholesterol and fatty acid metabolism.
20345851 The regulation of novel low-abundance transcript variants of human acyl-CoA binding protein, was analysed.
19874574 Observational study of gene-disease association. (HuGE Navigator)
19815704 Data suggest that the presence of gamma-glutamyl hydrolase and diazepam-binding inhibitor in urine serves as a rationale for developing them as urinary markers of clinical outcomes for patients treated with neoadjuvant chemotherapy.
19088433 ACBP is a transcriptional regulator of the HMGCS1 and HMGCR genes encoding rate-limiting enzymes of cholesterol synthesis pathway.
19086053 Observational study of gene-disease association. (HuGE Navigator)
18240651 study found a significant difference in the +529A/T (rs8192503) polymorphism allele frequency of the DBI gene between the alcoholics & controls; data suggest that mutation allele of the DBI gene polymorphism was one of the risk factors for alcoholism
17266179 Observational study of gene-disease association. (HuGE Navigator)
17262885 Observational study of gene-disease association. (HuGE Navigator)
17262885 we obtained evidence from two Caucasian study populations that the minor allele of ACBP rs2084202 might be associated with reduced risk of type 2 diabetes
17044054 Here high resolution crystal structures of human cytosolic liver ACBP, unliganded and liganded with a physiological ligand, myristoyl-CoA are described. The binding of the acyl-CoA molecule induces only few structural differences near the binding pocket
16908521 Acyl coenzyme A-binding protein has a role in augmenting bid-induced mitochondrial damage and cell death by activating mu-calpain
16904689 Observational study of gene-disease association. (HuGE Navigator)
16055366 Results identify new acyl-CoA binding protein transcripts in human and mouse tissues, generated by alternative first exon usage.
16042405 Data show for the first time in a physiological context that transgenic expression of acyl-coenzyme A binding protein may play a role in liver fatty acyl-coenzyme A metabolism.
14755437 Missense changes in diazepam binding inhibitorwere not associated with schizophrenia
12396232 ACBP has a role as an essential protein in human cells
12015306 PPRE in intron 1 of the ACBP gene is a bona fide PPARgamma-response element.

AA Sequence 

MSQAEFEKAAEEVRHLKTKPSDEEMLFIYGHYKQATVGDINTERPGMLDFTGKAKWDAWNELKGTSKEDA      1 - 70
MKAYINKVEELKKKYGI                                                          71 - 87
//

Text Mined References (70)

PMID Year Title
26290636 2015 Endozepine-4 levels are increased in hepatic coma.
25944712 2015 N-terminome analysis of the human mitochondrial proteome.
25898985 2015 Long-chain acyl-CoA esters in metabolism and signaling: Role of acyl-CoA binding proteins.
24819876 2014 Acyl-coenzyme A-binding protein regulates Beta-oxidation required for growth and survival of non-small cell lung cancer.
24818357 2014 Relationship between alcohol dependence and the DBI rs2276596 (C/A) polymorphism in Japanese.
24401326 2014 Diazepam binding inhibitor and dehydroepiandrosterone sulphate plasma levels in borderline personality disorder adolescents.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
24080521 2014 Acyl-CoA binding protein and epidermal barrier function.
23727119 2013 Endogenous positive allosteric modulation of GABA(A) receptors by diazepam binding inhibitor.
23533145 2013 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
23376485 2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine.
23251661 2012 Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
22814378 2012 N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.
21908771 2011 The first identification of lysine malonylation substrates and its regulatory enzyme.
21698759 2011 Identification of a novel human Acyl-CoA binding protein isoform with a unique C-terminal domain.
21448843 2011 Differential expression of alternative Acyl-CoA binding protein (ACBP) transcripts in an inducible human preadipocyte cell line.
21269460 2011 Initial characterization of the human central proteome.
21079819 2010 Expression, purification and functional characterization of recombinant human acyl-CoA-binding protein (ACBP) from erythroid cells.
20511713 2010 ACBP knockdown leads to down-regulation of genes encoding rate-limiting enzymes in cholesterol and fatty acid metabolism.
20458337 MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.
20345851 2011 Specific regulation of low-abundance transcript variants encoding human Acyl-CoA binding protein (ACBP) isoforms.
20068231 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
19874574 2009 Genetical genomic determinants of alcohol consumption in rats and humans.
19815704 2009 Genoproteomic mining of urothelial cancer suggests {gamma}-glutamyl hydrolase and diazepam-binding inhibitor as putative urinary markers of outcome after chemotherapy.
19608861 2009 Lysine acetylation targets protein complexes and co-regulates major cellular functions.
19413330 2009 Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.
19088433 2008 Transcriptional regulation of HMG-CoA synthase and HMG-CoA reductase genes by human ACBP.
19086053 2009 Identification of new putative susceptibility genes for several psychiatric disorders by association analysis of regulatory and non-synonymous SNPs of 306 genes involved in neurotransmission and neurodevelopment.
18240651 2007 The relationship between alcoholism and DBI gene polymorphism in Japanese--genotyping of the +529A/T in DBI gene polymorphism based on PCR.
17953517 2008 Acyl-CoA-binding protein (ACBP) localizes to the endoplasmic reticulum and Golgi in a ligand-dependent manner in mammalian cells.
17266179 2007 Candidate gene association study of type 2 diabetes in a nested case-control study of the EPIC-Potsdam cohort - role of fat assimilation.
17262885 2007 Association of acyl-CoA-binding protein (ACBP) single nucleotide polymorphisms and type 2 diabetes in two German study populations.
17207965 2007 hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes.
17044054 2007 High resolution crystal structures of unliganded and liganded human liver ACBP reveal a new mode of binding for the acyl-CoA ligand.
16908521 2006 Acyl coenzyme A-binding protein augments bid-induced mitochondrial damage and cell death by activating mu-calpain.
16904689 2007 Association of a Met88Val diazepam binding inhibitor (DBI) gene polymorphism and anxiety disorders with panic attacks.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16341674 2005 Transcriptome analysis of human gastric cancer.
16055366 2005 Identification of new acyl-CoA binding protein transcripts in human and mouse.
16042405 2005 Acyl-coenzyme A binding protein expression alters liver fatty acyl-coenzyme A metabolism.
15815621 2005 Generation and annotation of the DNA sequences of human chromosomes 2 and 4.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15342556 2004 Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions.
14755437 2004 Multiple missense mutations in the diazepam binding inhibitor (DBI) gene identified in schizophrenia but lack of disease association.
14602800 2003 Characterization of endozepines in the human testicular tissue: effect of triakontatetraneuropeptide on testosterone secretion.
12665801 2003 Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12396232 2002 Acyl-CoA binding protein is an essential protein in mammalian cell lines.
12015306 2002 The gene encoding the Acyl-CoA-binding protein is activated by peroxisome proliferator-activated receptor gamma through an intronic response element functionally conserved between humans and rodents.
10737800 2000 Shotgun sequencing of the human transcriptome with ORF expressed sequence tags.
9657356 1998 Diazepam binding inhibitor and total cholesterol plasma levels in cirrhosis and hepatocellular carcinoma.
9477145 1998 Diazepam binding inhibitor (DBI) in the plasma of pediatric and adult epileptic patients.
9022045 1997 The transcriptional and translational control of diazepam binding inhibitor expression in rat male germ-line cells.
8964506 1996 Structure of the rat gene encoding the multifunctional acyl-CoA-binding protein: conservation of intron 1 sequences in rodents and man. Addendum.
8634149 1996 A human gene encoding diazepam-binding inhibitor/acy1-CoA-binding protein: transcription and hormonal regulation in the androgen-sensitive human prostatic adenocarcinoma cell line LNCaP.
8396705 1993 ACTH-induced mitochondrial DBI receptor (MDR) and diazepam binding inhibitor (DBI) expression in adrenals of hypophysectomized rats is not cause-effect related to its immediate steroidogenic action.
8245508 1993 Expression of diazepam-binding inhibitor peptide in human skin: an immunohistochemical and ultrastructural study.
8043504 1994 The pharmacology of neurosteroidogenesis.
7794798 1995 Increased expression of diazepam binding inhibitor in human brain tumors.
7789980 1995 Molecular cloning and chromosomal localization of a pseudogene related to the human acyl-CoA binding protein/diazepam binding inhibitor.
7626442 1995 Role of the peripheral-type benzodiazepine receptor and the polypeptide diazepam binding inhibitor in steroidogenesis.
7534063 1995 The characterization of two diazepam binding inhibitor (DBI) transcripts in humans.
7527352 1994 Androgen regulation of the messenger RNA encoding diazepam-binding inhibitor/acyl-CoA-binding protein in the human prostatic adenocarcinoma cell line LNCaP.
3525533 1986 Complete amino acid sequences of bovine and human endozepines. Homology with rat diazepam binding inhibitor.
3413112 1988 Chromosomal localization of the human diazepam binding inhibitor gene.
3020548 1986 Cloning and expression of cDNA for human diazepam binding inhibitor, a natural ligand of an allosteric regulatory site of the gamma-aminobutyric acid type A receptor.
2881742 1987 Bovine and human cDNA sequences encoding a putative benzodiazepine receptor ligand.
1469708 1992 Acyl-CoA-binding protein/diazepam-binding inhibitor gene and pseudogenes. A typical housekeeping gene family.
1440058 1992 New chromosomal mapping assignments for argininosuccinate synthetase pseudogene 1, interferon-beta 3 gene, and the diazepam binding inhibitor gene.
1292782 1992 Purification and analysis of growth regulating proteins secreted by a human melanoma cell line.