Full text data of DBI
DBI
[Confidence: low (only semi-automatic identification from reviews)]
Acyl-CoA-binding protein; ACBP (Diazepam-binding inhibitor; DBI; Endozepine; EP)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Acyl-CoA-binding protein; ACBP (Diazepam-binding inhibitor; DBI; Endozepine; EP)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P07108
ID ACBP_HUMAN Reviewed; 87 AA.
AC P07108; B8ZWD2; B8ZWD6; B8ZWD7; P08869; Q4VWZ6; Q53SQ7; Q6IB48;
read moreAC Q9UCI8;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 146.
DE RecName: Full=Acyl-CoA-binding protein;
DE Short=ACBP;
DE AltName: Full=Diazepam-binding inhibitor;
DE Short=DBI;
DE AltName: Full=Endozepine;
DE Short=EP;
GN Name=DBI;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=3020548; DOI=10.1073/pnas.83.19.7547;
RA Gray P.W., Glaister D., Seeburg P.H., Guidotti A., Costa E.;
RT "Cloning and expression of cDNA for human diazepam binding inhibitor,
RT a natural ligand of an allosteric regulatory site of the gamma-
RT aminobutyric acid type A receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:7547-7551(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2881742;
RA Webb N.R., Rose T.M., Malik N., Marquardt H., Shoyab M., Todaro G.J.,
RA Lee D.C.;
RT "Bovine and human cDNA sequences encoding a putative benzodiazepine
RT receptor ligand.";
RL DNA 6:71-79(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND TISSUE SPECIFICITY.
RX PubMed=16055366; DOI=10.1016/j.biocel.2005.06.008;
RA Nitz I., Doering F., Schrezenmeir J., Burwinkel B.;
RT "Identification of new acyl-CoA binding protein transcripts in human
RT and mouse.";
RL Int. J. Biochem. Cell Biol. 37:2395-2405(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=21698759; DOI=10.1002/iub.471;
RA Ludewig A.H., Nitz I., Klapper M., Doring F.;
RT "Identification of a novel human Acyl-CoA binding protein isoform with
RT a unique C-terminal domain.";
RL IUBMB Life 63:547-552(2011).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 4 AND 5), ALTERNATIVE
RP SPLICING, AND ALTERNATIVE PROMOTER USAGE.
RX PubMed=20345851; DOI=10.1111/j.1582-4934.2010.01055.x;
RA Nitz I., Kruse M.L., Klapper M., Doring F.;
RT "Specific regulation of low-abundance transcript variants encoding
RT human Acyl-CoA binding protein (ACBP) isoforms.";
RL J. Cell. Mol. Med. 15:909-927(2011).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP PROTEIN SEQUENCE OF 2-87 (ISOFORM 1), AND ACETYLATION AT SER-2.
RC TISSUE=Brain;
RX PubMed=3525533;
RA Marquardt H., Todaro G.J., Shoyab M.;
RT "Complete amino acid sequences of bovine and human endozepines.
RT Homology with rat diazepam binding inhibitor.";
RL J. Biol. Chem. 261:9727-9731(1986).
RN [11]
RP PROTEIN SEQUENCE OF 2-14 (ISOFORM 1).
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [12]
RP PROTEIN SEQUENCE OF 26-30 AND 72-87.
RX PubMed=1292782;
RA Apfel R., Lottspeich F., Hoppe J., Behl C., Duerr G., Bogdahn U.;
RT "Purification and analysis of growth regulating proteins secreted by a
RT human melanoma cell line.";
RL Melanoma Res. 2:327-336(1992).
RN [13]
RP ALTERNATIVE SPLICING.
RX PubMed=7534063;
RA Kolmer M., Rovio A., Alho H.;
RT "The characterization of two diazepam binding inhibitor (DBI)
RT transcripts in humans.";
RL Biochem. J. 306:327-330(1995).
RN [14]
RP SUBCELLULAR LOCATION.
RX PubMed=17953517; DOI=10.1042/BJ20070559;
RA Hansen J.S., Faergeman N.J., Kragelund B.B., Knudsen J.;
RT "Acyl-CoA-binding protein (ACBP) localizes to the endoplasmic
RT reticulum and Golgi in a ligand-dependent manner in mammalian cells.";
RL Biochem. J. 410:463-472(2008).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2; LYS-8; LYS-19; LYS-55 AND
RP LYS-77, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-29, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP MALONYLATION AT LYS-55.
RX PubMed=21908771; DOI=10.1074/mcp.M111.012658;
RA Peng C., Lu Z., Xie Z., Cheng Z., Chen Y., Tan M., Luo H., Zhang Y.,
RA He W., Yang K., Zwaans B.M., Tishkoff D., Ho L., Lombard D., He T.C.,
RA Dai J., Verdin E., Ye Y., Zhao Y.;
RT "The first identification of lysine malonylation substrates and its
RT regulatory enzyme.";
RL Mol. Cell. Proteomics 10:M111.012658.01-M111.012658.12(2011).
RN [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) IN COMPLEX WITH ACYL-COENZYME A.
RX PubMed=17044054; DOI=10.1002/prot.21124;
RA Taskinen J.P., van Aalten D.M., Knudsen J., Wierenga R.K.;
RT "High resolution crystal structures of unliganded and liganded human
RT liver ACBP reveal a new mode of binding for the acyl-CoA ligand.";
RL Proteins 66:229-238(2007).
CC -!- FUNCTION: Binds medium- and long-chain acyl-CoA esters with very
CC high affinity and may function as an intracellular carrier of
CC acyl-CoA esters. It is also able to displace diazepam from the
CC benzodiazepine (BZD) recognition site located on the GABA type A
CC receptor. It is therefore possible that this protein also acts as
CC a neuropeptide to modulate the action of the GABA receptor.
CC -!- SUBUNIT: Monomer.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum. Golgi apparatus.
CC Note=Golgi localization is dependent on ligand binding.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=6;
CC Name=1; Synonyms=ACBP-1a, Short;
CC IsoId=P07108-1; Sequence=Displayed;
CC Name=2; Synonyms=ACBP-1b, Long;
CC IsoId=P07108-2; Sequence=VSP_000068;
CC Name=3; Synonyms=ACBP-1c;
CC IsoId=P07108-3; Sequence=VSP_038680;
CC Name=4; Synonyms=ACBP-1a1-g;
CC IsoId=P07108-4; Sequence=VSP_043437;
CC Name=5; Synonyms=ACBP-1g;
CC IsoId=P07108-5; Sequence=VSP_043438;
CC Name=6; Synonyms=ACBP-1e;
CC IsoId=P07108-6; Sequence=VSP_044114;
CC Note=Predominantly expressed in adipose tissue and hippocampus;
CC -!- TISSUE SPECIFICITY: Isoform 1 is ubiquitous, with a moderate
CC expression level. Isoform 2 is ubiquitous with high level in liver
CC and adipose tissue. Isoform 3 is ubiquitous with strong expression
CC in adipose tissue and heart.
CC -!- SIMILARITY: Belongs to the ACBP family.
CC -!- SIMILARITY: Contains 1 ACB (acyl-CoA-binding) domain.
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DR EMBL; M14200; AAA52171.1; -; mRNA.
DR EMBL; M15887; AAA35788.1; -; mRNA.
DR EMBL; FM213123; CAR82405.1; -; mRNA.
DR EMBL; FM213124; CAR82406.1; -; mRNA.
DR EMBL; FM213125; CAR82407.1; -; mRNA.
DR EMBL; FM213126; CAR82408.1; -; mRNA.
DR EMBL; FM213127; CAR82409.1; -; mRNA.
DR EMBL; FM213128; CAR82410.1; -; mRNA.
DR EMBL; FM213131; CAR82414.1; -; mRNA.
DR EMBL; CR456956; CAG33237.1; -; mRNA.
DR EMBL; AC016736; AAY14873.1; -; Genomic_DNA.
DR EMBL; CH471103; EAW95214.1; -; Genomic_DNA.
DR EMBL; BC006466; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC062996; AAH62996.1; -; mRNA.
DR EMBL; AM000001; CAJ00736.1; -; mRNA.
DR PIR; B26448; NZHU.
DR RefSeq; NP_001073331.1; NM_001079862.2.
DR RefSeq; NP_001073332.1; NM_001079863.1.
DR RefSeq; NP_001171488.1; NM_001178017.1.
DR RefSeq; NP_001171512.1; NM_001178041.2.
DR RefSeq; NP_001171513.1; NM_001178042.2.
DR RefSeq; NP_001269562.1; NM_001282633.1.
DR RefSeq; NP_001269563.1; NM_001282634.1.
DR RefSeq; NP_001269564.1; NM_001282635.1.
DR RefSeq; NP_065438.1; NM_020548.7.
DR UniGene; Hs.78888; -.
DR PDB; 2CB8; X-ray; 1.40 A; A/B=1-87.
DR PDB; 2FJ9; X-ray; 1.60 A; A=2-87.
DR PDBsum; 2CB8; -.
DR PDBsum; 2FJ9; -.
DR ProteinModelPortal; P07108; -.
DR SMR; P07108; 2-87.
DR IntAct; P07108; 9.
DR MINT; MINT-1394907; -.
DR STRING; 9606.ENSP00000311117; -.
DR PhosphoSite; P07108; -.
DR DMDM; 118276; -.
DR PaxDb; P07108; -.
DR PRIDE; P07108; -.
DR DNASU; 1622; -.
DR Ensembl; ENST00000311521; ENSP00000311117; ENSG00000155368.
DR Ensembl; ENST00000355857; ENSP00000348116; ENSG00000155368.
DR Ensembl; ENST00000393103; ENSP00000376815; ENSG00000155368.
DR Ensembl; ENST00000409094; ENSP00000386486; ENSG00000155368.
DR Ensembl; ENST00000535617; ENSP00000442917; ENSG00000155368.
DR Ensembl; ENST00000535757; ENSP00000439012; ENSG00000155368.
DR Ensembl; ENST00000542275; ENSP00000440698; ENSG00000155368.
DR GeneID; 1622; -.
DR KEGG; hsa:1622; -.
DR UCSC; uc002tlv.3; human.
DR CTD; 1622; -.
DR GeneCards; GC02P120124; -.
DR HGNC; HGNC:2690; DBI.
DR HPA; CAB008595; -.
DR MIM; 125950; gene.
DR neXtProt; NX_P07108; -.
DR PharmGKB; PA27158; -.
DR eggNOG; COG4281; -.
DR HOVERGEN; HBG000398; -.
DR KO; K08762; -.
DR OMA; ERPDNAT; -.
DR OrthoDB; EOG7SN8G8; -.
DR ChiTaRS; DBI; human.
DR EvolutionaryTrace; P07108; -.
DR GeneWiki; Diazepam_binding_inhibitor; -.
DR GenomeRNAi; 1622; -.
DR NextBio; 6658; -.
DR PRO; PR:P07108; -.
DR ArrayExpress; P07108; -.
DR Bgee; P07108; -.
DR CleanEx; HS_DBI; -.
DR Genevestigator; P07108; -.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0030156; F:benzodiazepine receptor binding; TAS:ProtInc.
DR GO; GO:0000062; F:fatty-acyl-CoA binding; IEA:InterPro.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0001942; P:hair follicle development; IEA:Ensembl.
DR GO; GO:0006810; P:transport; IEA:UniProtKB-KW.
DR GO; GO:0006641; P:triglyceride metabolic process; IEA:Ensembl.
DR Gene3D; 1.20.80.10; -; 1.
DR InterPro; IPR022408; Acyl-CoA-binding_prot_CS.
DR InterPro; IPR000582; Acyl-CoA-binding_protein.
DR InterPro; IPR014352; FERM/acyl-CoA-bd_prot_3-hlx.
DR Pfam; PF00887; ACBP; 1.
DR PRINTS; PR00689; ACOABINDINGP.
DR SUPFAM; SSF47027; SSF47027; 1.
DR PROSITE; PS00880; ACB_1; 1.
DR PROSITE; PS51228; ACB_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative promoter usage;
KW Alternative splicing; Complete proteome; Direct protein sequencing;
KW Endoplasmic reticulum; Golgi apparatus; Lipid-binding; Phosphoprotein;
KW Polymorphism; Reference proteome; Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 87 Acyl-CoA-binding protein.
FT /FTId=PRO_0000214004.
FT DOMAIN 2 87 ACB.
FT REGION 29 33 Acyl-CoA binding.
FT BINDING 14 14 Acyl-CoA.
FT BINDING 55 55 Acyl-CoA.
FT BINDING 74 74 Acyl-CoA.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 8 8 N6-acetyllysine.
FT MOD_RES 19 19 N6-acetyllysine.
FT MOD_RES 29 29 Phosphotyrosine.
FT MOD_RES 55 55 N6-acetyllysine; alternate.
FT MOD_RES 55 55 N6-malonyllysine; alternate.
FT MOD_RES 77 77 N6-acetyllysine.
FT VAR_SEQ 1 3 MSQ -> MWGDLWLLPPASANPGTGTE (in isoform
FT 2).
FT /FTId=VSP_000068.
FT VAR_SEQ 1 3 MSQ -> MPAF (in isoform 3).
FT /FTId=VSP_038680.
FT VAR_SEQ 1 3 MSQ -> MSQHRAGRRGGVGKRGVRGRELGGQGKYGAGCSE
FT CGTRRIAARGE (in isoform 4).
FT /FTId=VSP_043437.
FT VAR_SEQ 1 3 MSQ -> MERWGKGLHGLEERGDSVPIPKHRAGRRGGVGKR
FT GVRGRELGGQGKYGAGCSECGTRRIAARGE (in
FT isoform 5).
FT /FTId=VSP_043438.
FT VAR_SEQ 43 87 ERPGMLDFTGKAKWDAWNELKGTSKEDAMKAYINKVEELKK
FT KYGI -> GMQSGGWKGICSSKQAQQLRLEVPGNFTLKLPE
FT ALLFRWGMVMVPEVEKTMFRILSVSSSNRIQILVLEGLYWP
FT SPAATLY (in isoform 6).
FT /FTId=VSP_044114.
FT VARIANT 39 39 D -> N (in dbSNP:rs8192504).
FT /FTId=VAR_048160.
FT VARIANT 71 71 M -> V (in dbSNP:rs8192506).
FT /FTId=VAR_048161.
FT VARIANT 86 86 G -> R (in dbSNP:rs8192507).
FT /FTId=VAR_048162.
FT HELIX 3 12
FT HELIX 13 15
FT HELIX 22 36
FT HELIX 50 60
FT TURN 61 64
FT HELIX 67 85
SQ SEQUENCE 87 AA; 10044 MW; B343A309F1B1AE28 CRC64;
MSQAEFEKAA EEVRHLKTKP SDEEMLFIYG HYKQATVGDI NTERPGMLDF TGKAKWDAWN
ELKGTSKEDA MKAYINKVEE LKKKYGI
//
ID ACBP_HUMAN Reviewed; 87 AA.
AC P07108; B8ZWD2; B8ZWD6; B8ZWD7; P08869; Q4VWZ6; Q53SQ7; Q6IB48;
read moreAC Q9UCI8;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 146.
DE RecName: Full=Acyl-CoA-binding protein;
DE Short=ACBP;
DE AltName: Full=Diazepam-binding inhibitor;
DE Short=DBI;
DE AltName: Full=Endozepine;
DE Short=EP;
GN Name=DBI;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=3020548; DOI=10.1073/pnas.83.19.7547;
RA Gray P.W., Glaister D., Seeburg P.H., Guidotti A., Costa E.;
RT "Cloning and expression of cDNA for human diazepam binding inhibitor,
RT a natural ligand of an allosteric regulatory site of the gamma-
RT aminobutyric acid type A receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:7547-7551(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2881742;
RA Webb N.R., Rose T.M., Malik N., Marquardt H., Shoyab M., Todaro G.J.,
RA Lee D.C.;
RT "Bovine and human cDNA sequences encoding a putative benzodiazepine
RT receptor ligand.";
RL DNA 6:71-79(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND TISSUE SPECIFICITY.
RX PubMed=16055366; DOI=10.1016/j.biocel.2005.06.008;
RA Nitz I., Doering F., Schrezenmeir J., Burwinkel B.;
RT "Identification of new acyl-CoA binding protein transcripts in human
RT and mouse.";
RL Int. J. Biochem. Cell Biol. 37:2395-2405(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=21698759; DOI=10.1002/iub.471;
RA Ludewig A.H., Nitz I., Klapper M., Doring F.;
RT "Identification of a novel human Acyl-CoA binding protein isoform with
RT a unique C-terminal domain.";
RL IUBMB Life 63:547-552(2011).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 4 AND 5), ALTERNATIVE
RP SPLICING, AND ALTERNATIVE PROMOTER USAGE.
RX PubMed=20345851; DOI=10.1111/j.1582-4934.2010.01055.x;
RA Nitz I., Kruse M.L., Klapper M., Doring F.;
RT "Specific regulation of low-abundance transcript variants encoding
RT human Acyl-CoA binding protein (ACBP) isoforms.";
RL J. Cell. Mol. Med. 15:909-927(2011).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP PROTEIN SEQUENCE OF 2-87 (ISOFORM 1), AND ACETYLATION AT SER-2.
RC TISSUE=Brain;
RX PubMed=3525533;
RA Marquardt H., Todaro G.J., Shoyab M.;
RT "Complete amino acid sequences of bovine and human endozepines.
RT Homology with rat diazepam binding inhibitor.";
RL J. Biol. Chem. 261:9727-9731(1986).
RN [11]
RP PROTEIN SEQUENCE OF 2-14 (ISOFORM 1).
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [12]
RP PROTEIN SEQUENCE OF 26-30 AND 72-87.
RX PubMed=1292782;
RA Apfel R., Lottspeich F., Hoppe J., Behl C., Duerr G., Bogdahn U.;
RT "Purification and analysis of growth regulating proteins secreted by a
RT human melanoma cell line.";
RL Melanoma Res. 2:327-336(1992).
RN [13]
RP ALTERNATIVE SPLICING.
RX PubMed=7534063;
RA Kolmer M., Rovio A., Alho H.;
RT "The characterization of two diazepam binding inhibitor (DBI)
RT transcripts in humans.";
RL Biochem. J. 306:327-330(1995).
RN [14]
RP SUBCELLULAR LOCATION.
RX PubMed=17953517; DOI=10.1042/BJ20070559;
RA Hansen J.S., Faergeman N.J., Kragelund B.B., Knudsen J.;
RT "Acyl-CoA-binding protein (ACBP) localizes to the endoplasmic
RT reticulum and Golgi in a ligand-dependent manner in mammalian cells.";
RL Biochem. J. 410:463-472(2008).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2; LYS-8; LYS-19; LYS-55 AND
RP LYS-77, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-29, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP MALONYLATION AT LYS-55.
RX PubMed=21908771; DOI=10.1074/mcp.M111.012658;
RA Peng C., Lu Z., Xie Z., Cheng Z., Chen Y., Tan M., Luo H., Zhang Y.,
RA He W., Yang K., Zwaans B.M., Tishkoff D., Ho L., Lombard D., He T.C.,
RA Dai J., Verdin E., Ye Y., Zhao Y.;
RT "The first identification of lysine malonylation substrates and its
RT regulatory enzyme.";
RL Mol. Cell. Proteomics 10:M111.012658.01-M111.012658.12(2011).
RN [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) IN COMPLEX WITH ACYL-COENZYME A.
RX PubMed=17044054; DOI=10.1002/prot.21124;
RA Taskinen J.P., van Aalten D.M., Knudsen J., Wierenga R.K.;
RT "High resolution crystal structures of unliganded and liganded human
RT liver ACBP reveal a new mode of binding for the acyl-CoA ligand.";
RL Proteins 66:229-238(2007).
CC -!- FUNCTION: Binds medium- and long-chain acyl-CoA esters with very
CC high affinity and may function as an intracellular carrier of
CC acyl-CoA esters. It is also able to displace diazepam from the
CC benzodiazepine (BZD) recognition site located on the GABA type A
CC receptor. It is therefore possible that this protein also acts as
CC a neuropeptide to modulate the action of the GABA receptor.
CC -!- SUBUNIT: Monomer.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum. Golgi apparatus.
CC Note=Golgi localization is dependent on ligand binding.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=6;
CC Name=1; Synonyms=ACBP-1a, Short;
CC IsoId=P07108-1; Sequence=Displayed;
CC Name=2; Synonyms=ACBP-1b, Long;
CC IsoId=P07108-2; Sequence=VSP_000068;
CC Name=3; Synonyms=ACBP-1c;
CC IsoId=P07108-3; Sequence=VSP_038680;
CC Name=4; Synonyms=ACBP-1a1-g;
CC IsoId=P07108-4; Sequence=VSP_043437;
CC Name=5; Synonyms=ACBP-1g;
CC IsoId=P07108-5; Sequence=VSP_043438;
CC Name=6; Synonyms=ACBP-1e;
CC IsoId=P07108-6; Sequence=VSP_044114;
CC Note=Predominantly expressed in adipose tissue and hippocampus;
CC -!- TISSUE SPECIFICITY: Isoform 1 is ubiquitous, with a moderate
CC expression level. Isoform 2 is ubiquitous with high level in liver
CC and adipose tissue. Isoform 3 is ubiquitous with strong expression
CC in adipose tissue and heart.
CC -!- SIMILARITY: Belongs to the ACBP family.
CC -!- SIMILARITY: Contains 1 ACB (acyl-CoA-binding) domain.
CC -----------------------------------------------------------------------
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DR EMBL; M14200; AAA52171.1; -; mRNA.
DR EMBL; M15887; AAA35788.1; -; mRNA.
DR EMBL; FM213123; CAR82405.1; -; mRNA.
DR EMBL; FM213124; CAR82406.1; -; mRNA.
DR EMBL; FM213125; CAR82407.1; -; mRNA.
DR EMBL; FM213126; CAR82408.1; -; mRNA.
DR EMBL; FM213127; CAR82409.1; -; mRNA.
DR EMBL; FM213128; CAR82410.1; -; mRNA.
DR EMBL; FM213131; CAR82414.1; -; mRNA.
DR EMBL; CR456956; CAG33237.1; -; mRNA.
DR EMBL; AC016736; AAY14873.1; -; Genomic_DNA.
DR EMBL; CH471103; EAW95214.1; -; Genomic_DNA.
DR EMBL; BC006466; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC062996; AAH62996.1; -; mRNA.
DR EMBL; AM000001; CAJ00736.1; -; mRNA.
DR PIR; B26448; NZHU.
DR RefSeq; NP_001073331.1; NM_001079862.2.
DR RefSeq; NP_001073332.1; NM_001079863.1.
DR RefSeq; NP_001171488.1; NM_001178017.1.
DR RefSeq; NP_001171512.1; NM_001178041.2.
DR RefSeq; NP_001171513.1; NM_001178042.2.
DR RefSeq; NP_001269562.1; NM_001282633.1.
DR RefSeq; NP_001269563.1; NM_001282634.1.
DR RefSeq; NP_001269564.1; NM_001282635.1.
DR RefSeq; NP_065438.1; NM_020548.7.
DR UniGene; Hs.78888; -.
DR PDB; 2CB8; X-ray; 1.40 A; A/B=1-87.
DR PDB; 2FJ9; X-ray; 1.60 A; A=2-87.
DR PDBsum; 2CB8; -.
DR PDBsum; 2FJ9; -.
DR ProteinModelPortal; P07108; -.
DR SMR; P07108; 2-87.
DR IntAct; P07108; 9.
DR MINT; MINT-1394907; -.
DR STRING; 9606.ENSP00000311117; -.
DR PhosphoSite; P07108; -.
DR DMDM; 118276; -.
DR PaxDb; P07108; -.
DR PRIDE; P07108; -.
DR DNASU; 1622; -.
DR Ensembl; ENST00000311521; ENSP00000311117; ENSG00000155368.
DR Ensembl; ENST00000355857; ENSP00000348116; ENSG00000155368.
DR Ensembl; ENST00000393103; ENSP00000376815; ENSG00000155368.
DR Ensembl; ENST00000409094; ENSP00000386486; ENSG00000155368.
DR Ensembl; ENST00000535617; ENSP00000442917; ENSG00000155368.
DR Ensembl; ENST00000535757; ENSP00000439012; ENSG00000155368.
DR Ensembl; ENST00000542275; ENSP00000440698; ENSG00000155368.
DR GeneID; 1622; -.
DR KEGG; hsa:1622; -.
DR UCSC; uc002tlv.3; human.
DR CTD; 1622; -.
DR GeneCards; GC02P120124; -.
DR HGNC; HGNC:2690; DBI.
DR HPA; CAB008595; -.
DR MIM; 125950; gene.
DR neXtProt; NX_P07108; -.
DR PharmGKB; PA27158; -.
DR eggNOG; COG4281; -.
DR HOVERGEN; HBG000398; -.
DR KO; K08762; -.
DR OMA; ERPDNAT; -.
DR OrthoDB; EOG7SN8G8; -.
DR ChiTaRS; DBI; human.
DR EvolutionaryTrace; P07108; -.
DR GeneWiki; Diazepam_binding_inhibitor; -.
DR GenomeRNAi; 1622; -.
DR NextBio; 6658; -.
DR PRO; PR:P07108; -.
DR ArrayExpress; P07108; -.
DR Bgee; P07108; -.
DR CleanEx; HS_DBI; -.
DR Genevestigator; P07108; -.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0030156; F:benzodiazepine receptor binding; TAS:ProtInc.
DR GO; GO:0000062; F:fatty-acyl-CoA binding; IEA:InterPro.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0001942; P:hair follicle development; IEA:Ensembl.
DR GO; GO:0006810; P:transport; IEA:UniProtKB-KW.
DR GO; GO:0006641; P:triglyceride metabolic process; IEA:Ensembl.
DR Gene3D; 1.20.80.10; -; 1.
DR InterPro; IPR022408; Acyl-CoA-binding_prot_CS.
DR InterPro; IPR000582; Acyl-CoA-binding_protein.
DR InterPro; IPR014352; FERM/acyl-CoA-bd_prot_3-hlx.
DR Pfam; PF00887; ACBP; 1.
DR PRINTS; PR00689; ACOABINDINGP.
DR SUPFAM; SSF47027; SSF47027; 1.
DR PROSITE; PS00880; ACB_1; 1.
DR PROSITE; PS51228; ACB_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative promoter usage;
KW Alternative splicing; Complete proteome; Direct protein sequencing;
KW Endoplasmic reticulum; Golgi apparatus; Lipid-binding; Phosphoprotein;
KW Polymorphism; Reference proteome; Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 87 Acyl-CoA-binding protein.
FT /FTId=PRO_0000214004.
FT DOMAIN 2 87 ACB.
FT REGION 29 33 Acyl-CoA binding.
FT BINDING 14 14 Acyl-CoA.
FT BINDING 55 55 Acyl-CoA.
FT BINDING 74 74 Acyl-CoA.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 8 8 N6-acetyllysine.
FT MOD_RES 19 19 N6-acetyllysine.
FT MOD_RES 29 29 Phosphotyrosine.
FT MOD_RES 55 55 N6-acetyllysine; alternate.
FT MOD_RES 55 55 N6-malonyllysine; alternate.
FT MOD_RES 77 77 N6-acetyllysine.
FT VAR_SEQ 1 3 MSQ -> MWGDLWLLPPASANPGTGTE (in isoform
FT 2).
FT /FTId=VSP_000068.
FT VAR_SEQ 1 3 MSQ -> MPAF (in isoform 3).
FT /FTId=VSP_038680.
FT VAR_SEQ 1 3 MSQ -> MSQHRAGRRGGVGKRGVRGRELGGQGKYGAGCSE
FT CGTRRIAARGE (in isoform 4).
FT /FTId=VSP_043437.
FT VAR_SEQ 1 3 MSQ -> MERWGKGLHGLEERGDSVPIPKHRAGRRGGVGKR
FT GVRGRELGGQGKYGAGCSECGTRRIAARGE (in
FT isoform 5).
FT /FTId=VSP_043438.
FT VAR_SEQ 43 87 ERPGMLDFTGKAKWDAWNELKGTSKEDAMKAYINKVEELKK
FT KYGI -> GMQSGGWKGICSSKQAQQLRLEVPGNFTLKLPE
FT ALLFRWGMVMVPEVEKTMFRILSVSSSNRIQILVLEGLYWP
FT SPAATLY (in isoform 6).
FT /FTId=VSP_044114.
FT VARIANT 39 39 D -> N (in dbSNP:rs8192504).
FT /FTId=VAR_048160.
FT VARIANT 71 71 M -> V (in dbSNP:rs8192506).
FT /FTId=VAR_048161.
FT VARIANT 86 86 G -> R (in dbSNP:rs8192507).
FT /FTId=VAR_048162.
FT HELIX 3 12
FT HELIX 13 15
FT HELIX 22 36
FT HELIX 50 60
FT TURN 61 64
FT HELIX 67 85
SQ SEQUENCE 87 AA; 10044 MW; B343A309F1B1AE28 CRC64;
MSQAEFEKAA EEVRHLKTKP SDEEMLFIYG HYKQATVGDI NTERPGMLDF TGKAKWDAWN
ELKGTSKEDA MKAYINKVEE LKKKYGI
//
MIM
125950
*RECORD*
*FIELD* NO
125950
*FIELD* TI
*125950 DIAZEPAM BINDING INHIBITOR; DBI
;;ACYL-CoA BINDING PROTEIN; ACBP;;
CHOLECYSTOKININ-RELEASING PEPTIDE, TRYPSIN-SENSITIVE
read more*FIELD* TX
DESCRIPTION
Benzodiazepines modulate signal transduction at type A GABA
(gamma-aminobutyric acid) receptors (137160) located in brain synapses.
GABA is the predominant inhibitory neurotransmitter of the mammalian
central nervous system. This receptor binds GABA, beta-carbolines, and
benzodiazepines with high affinity and a chloride ion channel.
Benzodiazepines prolong the chloride ion channel opening burst elicited
by GABA and thereby enhance GABA-mediated inhibitory responses. This
facilitation plays a role in reducing pathologic anxiety. An endogenous
ligand has been identified that is recognized by the
beta-carboline/benzodiazepine recognition site located in the GABA
receptor. This ligand, diazepam binding inhibitor (DBI), is a protein of
about 11 kD that displaces beta-carbolines and benzodiazepines bound to
brain membrane fractions in vitro. DBI or a derivative small
neuropeptide is thought to downregulate the effects of GABA (summary by
Gray et al., 1986).
CLONING
Gray et al. (1986) isolated a cDNA clone that encodes human DBI. A
polypeptide related to DBI, with similar binding activity to diazepam,
has been isolated from human and bovine brain. This protein, called
endozepine, contains 86 amino residues. Webb et al. (1987) cloned
endozepine cDNAs from bovine and human libraries and found 93% homology
in the coding regions of the bovine and human forms. The message is 650
nucleotides long. Northern analysis using the cloned cDNA demonstrated
that the message is expressed in heart, liver, and spleen, in addition
to brain.
Diazepam binding inhibitor is also known as acyl-CoA-binding protein
(ACBP). Rose et al. (1992) cloned the homologous gene from the budding
yeast Saccharomyces cerevisiae. The yeast gene contains no introns and
encodes a polypeptide of 87 amino acids (including the initiating
methionine), identical in length to the human gene product with 48%
conservation of amino acid residues. The most highly conserved domain
comprises 7 contiguous residues that are identical in all known protein
species from yeast, birds, and mammals. This domain constitutes the
hydrophobic binding site for acyl-CoA esters and is located within the
second helical region of the molecule. The presence of a highly
conserved gene in a primitive organism such as yeast supports its basic
biologic role as an acyl-CoA-binding protein and suggests that many of
the biologic functions attributed to it in higher organisms may result
from its ability to interact with acyl-CoA. Rose et al. (1992)
designated the yeast gene ACB, for acyl-CoA binding.
GENE FUNCTION
Benzodiazepine receptors unassociated with the GABA receptor complex,
and distinct from those seen in association with the central nervous
system, have been identified in peripheral tissues. Anholt et al. (1986)
presented evidence that these peripheral receptors are localized on the
mitochondrial outer membrane. Webb et al. (1987) speculated that the
role of endozepine in peripheral tissues is to interact with this
receptor.
Herzig et al. (1996) isolated a trypsin-sensitive cholecystokinin (CCK;
118440)-releasing peptide (CCK-RP) from porcine and rat intestinal
mucosa. At the same time, Spannagel et al. (1996) purified a luminal
CCK-releasing factor from rat intestinal secretions. Herzig et al.
(1996) found that the amino acid sequence of CCK-RP was identical to
that of diazepam-binding inhibitor. Li et al. (2000) demonstrated that
DBI mediates the feedback regulation of pancreatic secretion and the
postprandial release of cholecystokinin.
MAPPING
By in situ hybridization and Southern blot analysis of human-mouse
hybrid cell lines, DeBernardi et al. (1988) mapped the DBI gene to
2q12-q21. By in situ hybridization, secondary signals were observed on
other chromosomes, mainly nos. 5, 6, 11 and 14. The cell hybrid studies
suggested that 3 homologous sequences are on other chromosomes.
Todd and Naylor (1992) used the nucleotide sequence of the DBI gene as
recorded in the GenBank database to generate DNA primers to amplify
specific sequences by PCR. The primers failed to amplify DNA sequences
when used to analyze microcell hybrid clones containing human chromosome
2. Therefore, in order to map the gene, a panel of somatic cell hybrids
was analyzed by PCR. The results of this experiment placed DBI on human
chromosome 6. Hybrid cells contained the DBI gene only when the region
6q12-q21 was present.
Gersuk et al. (1995) cloned and sequenced a pseudogene of ACBP/DBI. The
locus, called DIBP1, mapped to chromosome 6. The authors concluded that
the functional gene must be located on chromosome 2.
*FIELD* RF
1. Anholt, R. R. H.; Pederson, P. L.; Desouza, E. B.; Synder, S. H.
: The peripheral-type benzodiazepine receptor: localization to the
mitochondrial outer membrane. J. Biol. Chem. 261: 576-583, 1986.
2. DeBernardi, M. A.; Crowe, R. R.; Mocchetti, I.; Shows, T. B.; Eddy,
R. L.; Costa, E.: Chromosomal localization of the human diazepam
binding inhibitor gene. Proc. Nat. Acad. Sci. 85: 6561-6565, 1988.
3. Gersuk, V. H.; Rose, T. M.; Todaro, G. J.: Molecular cloning and
chromosomal localization of a pseudogene related to the human acyl-CoA
binding protein/diazepam binding inhibitor. Genomics 25: 469-476,
1995.
4. Gray, P. W.; Glaister, D.; Seeburg, P. H.; Guidotti, A.; Costa,
E.: 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. Proc. Nat. Acad. Sci. 83: 7547-7551, 1986.
5. Herzig, K. H.; Schon, I.; Tatemoto, K.; Ohe, Y.; Li, Y.; Folsch,
U. R.; Owyang, C.: Diazepam binding inhibitor is a potent cholecystokinin-releasing
peptide in the intestine. Proc. Nat. Acad. Sci. 93: 7927-7932, 1996.
Note: Erratum: Proc. Nat. Acad. Sci. 93: 14214 only, 1996.
6. Li, Y.; Hao, Y.; Owyang, C.: Diazepam-binding inhibitor mediates
feedback regulation of pancreatic secretion and postprandial release
of cholecystokinin. J. Clin. Invest. 105: 351-359, 2000.
7. Rose, T. M.; Schultz, E. R.; Todaro, G. J.: Molecular cloning
of the gene for the yeast homolog (ACB) of diazepam binding inhibitor/endozepine/acyl-CoA-binding
protein. Proc. Nat. Acad. Sci. 89: 11287-11291, 1992.
8. Spannagel, A. W.; Green, G. M.; Guan, D.; Liddle, R. A.; Faull,
K.; Reeve, J. R.: Purification and characterization of a luminal
cholecystokinin-releasing factor from rat intestinal secretion. Proc.
Nat. Acad. Sci. 93: 4415-4420, 1996.
9. Todd, S.; Naylor, S. L.: New chromosomal mapping assignments for
argininosuccinate synthetase pseudogene 1, interferon-beta-3 gene,
and the diazepam binding inhibitor gene. Somat. Cell Molec. Genet. 18:
381-385, 1992.
10. Webb, N. R.; Rose, T. M.; Malik, N.; Marquardt, H.; Shoyab, M.;
Todaro, G. J.; Lee, D. C.: Bovine and human cDNA sequences encoding
a putative benzodiazepine receptor ligand. DNA 6: 71-79, 1987.
*FIELD* CN
Victor A. McKusick - updated: 2/18/2000
*FIELD* CD
Victor A. McKusick: 12/15/1986
*FIELD* ED
terry: 06/06/2012
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alopez: 8/3/2010
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mcapotos: 3/23/2000
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mimadm: 6/25/1994
carol: 1/22/1993
carol: 1/7/1993
*RECORD*
*FIELD* NO
125950
*FIELD* TI
*125950 DIAZEPAM BINDING INHIBITOR; DBI
;;ACYL-CoA BINDING PROTEIN; ACBP;;
CHOLECYSTOKININ-RELEASING PEPTIDE, TRYPSIN-SENSITIVE
read more*FIELD* TX
DESCRIPTION
Benzodiazepines modulate signal transduction at type A GABA
(gamma-aminobutyric acid) receptors (137160) located in brain synapses.
GABA is the predominant inhibitory neurotransmitter of the mammalian
central nervous system. This receptor binds GABA, beta-carbolines, and
benzodiazepines with high affinity and a chloride ion channel.
Benzodiazepines prolong the chloride ion channel opening burst elicited
by GABA and thereby enhance GABA-mediated inhibitory responses. This
facilitation plays a role in reducing pathologic anxiety. An endogenous
ligand has been identified that is recognized by the
beta-carboline/benzodiazepine recognition site located in the GABA
receptor. This ligand, diazepam binding inhibitor (DBI), is a protein of
about 11 kD that displaces beta-carbolines and benzodiazepines bound to
brain membrane fractions in vitro. DBI or a derivative small
neuropeptide is thought to downregulate the effects of GABA (summary by
Gray et al., 1986).
CLONING
Gray et al. (1986) isolated a cDNA clone that encodes human DBI. A
polypeptide related to DBI, with similar binding activity to diazepam,
has been isolated from human and bovine brain. This protein, called
endozepine, contains 86 amino residues. Webb et al. (1987) cloned
endozepine cDNAs from bovine and human libraries and found 93% homology
in the coding regions of the bovine and human forms. The message is 650
nucleotides long. Northern analysis using the cloned cDNA demonstrated
that the message is expressed in heart, liver, and spleen, in addition
to brain.
Diazepam binding inhibitor is also known as acyl-CoA-binding protein
(ACBP). Rose et al. (1992) cloned the homologous gene from the budding
yeast Saccharomyces cerevisiae. The yeast gene contains no introns and
encodes a polypeptide of 87 amino acids (including the initiating
methionine), identical in length to the human gene product with 48%
conservation of amino acid residues. The most highly conserved domain
comprises 7 contiguous residues that are identical in all known protein
species from yeast, birds, and mammals. This domain constitutes the
hydrophobic binding site for acyl-CoA esters and is located within the
second helical region of the molecule. The presence of a highly
conserved gene in a primitive organism such as yeast supports its basic
biologic role as an acyl-CoA-binding protein and suggests that many of
the biologic functions attributed to it in higher organisms may result
from its ability to interact with acyl-CoA. Rose et al. (1992)
designated the yeast gene ACB, for acyl-CoA binding.
GENE FUNCTION
Benzodiazepine receptors unassociated with the GABA receptor complex,
and distinct from those seen in association with the central nervous
system, have been identified in peripheral tissues. Anholt et al. (1986)
presented evidence that these peripheral receptors are localized on the
mitochondrial outer membrane. Webb et al. (1987) speculated that the
role of endozepine in peripheral tissues is to interact with this
receptor.
Herzig et al. (1996) isolated a trypsin-sensitive cholecystokinin (CCK;
118440)-releasing peptide (CCK-RP) from porcine and rat intestinal
mucosa. At the same time, Spannagel et al. (1996) purified a luminal
CCK-releasing factor from rat intestinal secretions. Herzig et al.
(1996) found that the amino acid sequence of CCK-RP was identical to
that of diazepam-binding inhibitor. Li et al. (2000) demonstrated that
DBI mediates the feedback regulation of pancreatic secretion and the
postprandial release of cholecystokinin.
MAPPING
By in situ hybridization and Southern blot analysis of human-mouse
hybrid cell lines, DeBernardi et al. (1988) mapped the DBI gene to
2q12-q21. By in situ hybridization, secondary signals were observed on
other chromosomes, mainly nos. 5, 6, 11 and 14. The cell hybrid studies
suggested that 3 homologous sequences are on other chromosomes.
Todd and Naylor (1992) used the nucleotide sequence of the DBI gene as
recorded in the GenBank database to generate DNA primers to amplify
specific sequences by PCR. The primers failed to amplify DNA sequences
when used to analyze microcell hybrid clones containing human chromosome
2. Therefore, in order to map the gene, a panel of somatic cell hybrids
was analyzed by PCR. The results of this experiment placed DBI on human
chromosome 6. Hybrid cells contained the DBI gene only when the region
6q12-q21 was present.
Gersuk et al. (1995) cloned and sequenced a pseudogene of ACBP/DBI. The
locus, called DIBP1, mapped to chromosome 6. The authors concluded that
the functional gene must be located on chromosome 2.
*FIELD* RF
1. Anholt, R. R. H.; Pederson, P. L.; Desouza, E. B.; Synder, S. H.
: The peripheral-type benzodiazepine receptor: localization to the
mitochondrial outer membrane. J. Biol. Chem. 261: 576-583, 1986.
2. DeBernardi, M. A.; Crowe, R. R.; Mocchetti, I.; Shows, T. B.; Eddy,
R. L.; Costa, E.: Chromosomal localization of the human diazepam
binding inhibitor gene. Proc. Nat. Acad. Sci. 85: 6561-6565, 1988.
3. Gersuk, V. H.; Rose, T. M.; Todaro, G. J.: Molecular cloning and
chromosomal localization of a pseudogene related to the human acyl-CoA
binding protein/diazepam binding inhibitor. Genomics 25: 469-476,
1995.
4. Gray, P. W.; Glaister, D.; Seeburg, P. H.; Guidotti, A.; Costa,
E.: 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. Proc. Nat. Acad. Sci. 83: 7547-7551, 1986.
5. Herzig, K. H.; Schon, I.; Tatemoto, K.; Ohe, Y.; Li, Y.; Folsch,
U. R.; Owyang, C.: Diazepam binding inhibitor is a potent cholecystokinin-releasing
peptide in the intestine. Proc. Nat. Acad. Sci. 93: 7927-7932, 1996.
Note: Erratum: Proc. Nat. Acad. Sci. 93: 14214 only, 1996.
6. Li, Y.; Hao, Y.; Owyang, C.: Diazepam-binding inhibitor mediates
feedback regulation of pancreatic secretion and postprandial release
of cholecystokinin. J. Clin. Invest. 105: 351-359, 2000.
7. Rose, T. M.; Schultz, E. R.; Todaro, G. J.: Molecular cloning
of the gene for the yeast homolog (ACB) of diazepam binding inhibitor/endozepine/acyl-CoA-binding
protein. Proc. Nat. Acad. Sci. 89: 11287-11291, 1992.
8. Spannagel, A. W.; Green, G. M.; Guan, D.; Liddle, R. A.; Faull,
K.; Reeve, J. R.: Purification and characterization of a luminal
cholecystokinin-releasing factor from rat intestinal secretion. Proc.
Nat. Acad. Sci. 93: 4415-4420, 1996.
9. Todd, S.; Naylor, S. L.: New chromosomal mapping assignments for
argininosuccinate synthetase pseudogene 1, interferon-beta-3 gene,
and the diazepam binding inhibitor gene. Somat. Cell Molec. Genet. 18:
381-385, 1992.
10. Webb, N. R.; Rose, T. M.; Malik, N.; Marquardt, H.; Shoyab, M.;
Todaro, G. J.; Lee, D. C.: Bovine and human cDNA sequences encoding
a putative benzodiazepine receptor ligand. DNA 6: 71-79, 1987.
*FIELD* CN
Victor A. McKusick - updated: 2/18/2000
*FIELD* CD
Victor A. McKusick: 12/15/1986
*FIELD* ED
terry: 06/06/2012
alopez: 3/5/2012
alopez: 8/3/2010
mcapotos: 4/10/2001
terry: 10/6/2000
mcapotos: 3/24/2000
mcapotos: 3/23/2000
terry: 2/18/2000
terry: 6/3/1995
mark: 5/19/1995
carol: 3/29/1995
mimadm: 6/25/1994
carol: 1/22/1993
carol: 1/7/1993