Full text data of TSPO
TSPO
(BZRP, MBR)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Translocator protein (Mitochondrial benzodiazepine receptor; PKBS; Peripheral-type benzodiazepine receptor; PBR)
Translocator protein (Mitochondrial benzodiazepine receptor; PKBS; Peripheral-type benzodiazepine receptor; PBR)
UniProt
P30536
ID TSPOA_HUMAN Reviewed; 169 AA.
AC P30536; Q53Y59; Q6ICF9; Q96TF6;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 30-NOV-2010, sequence version 3.
DT 22-JAN-2014, entry version 124.
DE RecName: Full=Translocator protein;
DE AltName: Full=Mitochondrial benzodiazepine receptor;
DE AltName: Full=PKBS;
DE AltName: Full=Peripheral-type benzodiazepine receptor;
DE Short=PBR;
GN Name=TSPO; Synonyms=BZRP, MBR;
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 1), AND VARIANTS ALA-147 AND
RP HIS-162.
RX PubMed=1847678; DOI=10.1111/j.1432-1033.1991.tb15707.x;
RA Riond J., Mattei M.-G., Kaghad M., Dumont X., Guillemot J.-C.,
RA le Fur G., Caput D., Ferrara P.;
RT "Molecular cloning and chromosomal localization of a human peripheral-
RT type benzodiazepine receptor.";
RL Eur. J. Biochem. 195:305-311(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7721091; DOI=10.1016/0378-1119(94)00817-C;
RA Yakovlev A.G., Ruffo M., Jurka J., Krueger K.E.;
RT "Comparison of repetitive elements in the third intron of human and
RT rodent mitochondrial benzodiazepine receptor-encoding genes.";
RL Gene 155:201-205(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=16189298; DOI=10.1124/mol.105.015289;
RA Costa B., Salvetti A., Rossi L., Spinetti F., Lena A., Chelli B.,
RA Rechichi M., Da Pozzo E., Gremigni V., Martini C.;
RT "Peripheral benzodiazepine receptor: characterization in human T-
RT lymphoma Jurkat cells.";
RL Mol. Pharmacol. 69:37-44(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS
RP ALA-147 AND HIS-162.
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS
RP ALA-147 AND HIS-162.
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ALA-147 AND GLN-169.
RG NIEHS SNPs program;
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M.,
RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K.,
RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J.,
RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G.,
RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R.,
RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E.,
RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G.,
RA Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S.,
RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A.,
RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M.,
RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T.,
RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J.,
RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T.,
RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T.,
RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L.,
RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M.,
RA Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J.,
RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S.,
RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T.,
RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I.,
RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H.,
RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L.,
RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z.,
RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P.,
RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S.,
RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J.,
RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T.,
RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J.,
RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S.,
RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E.,
RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P.,
RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E.,
RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X.,
RA Khan A.S., Lane L., Tilahun Y., Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph;
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 [9]
RP INTERACTION WITH BZRAP1.
RC TISSUE=Brain;
RX PubMed=9915832; DOI=10.1074/jbc.274.5.2938;
RA Galiegue S., Jbilo O., Combes T., Bribes E., Carayon P., Le Fur G.,
RA Casellas P.;
RT "Cloning and characterization of PRAX-1. A new protein that
RT specifically interacts with the peripheral benzodiazepine receptor.";
RL J. Biol. Chem. 274:2938-2952(1999).
RN [10]
RP NOMENCLATURE.
RX PubMed=16822554; DOI=10.1016/j.tips.2006.06.005;
RA Papadopoulos V., Baraldi M., Guilarte T.R., Knudsen T.B.,
RA Lacapere J.-J., Lindemann P., Norenberg M.D., Nutt D., Weizman A.,
RA Zhang M.-R., Gavish M.;
RT "Translocator protein (18kDa): new nomenclature for the peripheral-
RT type benzodiazepine receptor based on its structure and molecular
RT function.";
RL Trends Pharmacol. Sci. 27:402-409(2006).
RN [11]
RP INTERACTION WITH MOST-1.
RX PubMed=17143515;
RA Tan J.M.M., Chow V.T.K.;
RT "Cellular expression, localization and interactions of the product of
RT the human MOST-1 gene associated with breast and prostate cancers.";
RL Int. J. Oncol. 30:81-89(2007).
RN [12]
RP TISSUE SPECIFICITY.
RX PubMed=20600583; DOI=10.1016/j.mce.2010.06.013;
RA Batarseh A., Papadopoulos V.;
RT "Regulation of translocator protein 18 kDa (TSPO) expression in health
RT and disease states.";
RL Mol. Cell. Endocrinol. 327:1-12(2010).
RN [13]
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 [14]
RP VARIANTS ALA-147 AND HIS-162.
RX PubMed=11215759; DOI=10.1007/s007020070090;
RA Kurumaji A., Nomoto H., Yoshikawa T., Okubo Y., Toru M.;
RT "An association study between two missense variations of the
RT benzodiazepine receptor (peripheral) gene and schizophrenia in a
RT Japanese sample.";
RL J. Neural Transm. 107:491-500(2000).
RN [15]
RP VARIANTS ALA-147 AND HIS-162.
RX PubMed=11304832; DOI=10.1002/ajmg.1194;
RA Kurumaji A., Nomoto H., Yamada K., Yoshikawa T., Toru M.;
RT "No association of two missense variations of the benzodiazepine
RT receptor (peripheral) gene and mood disorders in a Japanese sample.";
RL Am. J. Med. Genet. 105:172-175(2001).
CC -!- FUNCTION: Responsible for the manifestation of peripheral-type
CC benzodiazepine recognition sites and is most likely to comprise
CC binding domains for benzodiazepines and isoquinoline carboxamides.
CC May play a role in the transport of porphyrins and heme. Plays a
CC role in the transport of cholesterol across mitochondrial
CC membranes in steroidogenic cells (By similarity).
CC -!- SUBUNIT: Interacts with BZRAP1 (By similarity). May interact with
CC STAR (By similarity). Interacts with MOST-1.
CC -!- SUBCELLULAR LOCATION: Mitochondrion membrane; Multi-pass membrane
CC protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P30536-1; Sequence=Displayed;
CC Name=2; Synonyms=PBR-S;
CC IsoId=B1AH88-1; Sequence=External;
CC Note=No experimental confirmation available. The relatively low
CC levels of the corresponding mRNA suggest that it might represent
CC errors of the splicing machinery. In addition, isoform 2 is
CC derived from a different reading frame, compared to isoform 1
CC and lacks homolog support;
CC -!- TISSUE SPECIFICITY: Found in many tissue types. Expressed at the
CC highest levels under normal conditions in tissues that synthesize
CC steroids.
CC -!- SIMILARITY: Belongs to the TspO/BZRP family.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/bzrp/";
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DR EMBL; M36035; AAA03652.1; -; mRNA.
DR EMBL; U12421; AAA83252.1; -; Genomic_DNA.
DR EMBL; AY998017; AAY45787.1; -; mRNA.
DR EMBL; BT006949; AAP35595.1; -; mRNA.
DR EMBL; CR456409; CAG30295.1; -; mRNA.
DR EMBL; AY383615; AAQ75703.1; -; Genomic_DNA.
DR EMBL; Z82214; CAB55884.1; -; Genomic_DNA.
DR EMBL; BC001110; AAH01110.1; -; mRNA.
DR PIR; I38724; I38724.
DR PIR; JE0149; JE0149.
DR PIR; S14257; S14257.
DR RefSeq; NP_000705.2; NM_000714.5.
DR RefSeq; NP_001243459.1; NM_001256530.1.
DR RefSeq; NP_001243460.1; NM_001256531.1.
DR UniGene; Hs.202; -.
DR ProteinModelPortal; P30536; -.
DR BindingDB; P30536; -.
DR ChEMBL; CHEMBL5742; -.
DR DrugBank; DB00546; Adinazolam.
DR DrugBank; DB00404; Alprazolam.
DR DrugBank; DB01178; Chlormezanone.
DR DrugBank; DB01594; Cinolazepam.
DR DrugBank; DB01068; Clonazepam.
DR DrugBank; DB00628; Clorazepate.
DR DrugBank; DB01559; Clotiazepam.
DR DrugBank; DB00829; Diazepam.
DR DrugBank; DB00822; Disulfiram.
DR DrugBank; DB01215; Estazolam.
DR DrugBank; DB00402; Eszopiclone.
DR DrugBank; DB01544; Flunitrazepam.
DR DrugBank; DB00801; Halazepam.
DR DrugBank; DB00186; Lorazepam.
DR DrugBank; DB00231; Temazepam.
DR DrugBank; DB00897; Triazolam.
DR DrugBank; DB00962; Zaleplon.
DR DrugBank; DB00425; Zolpidem.
DR DrugBank; DB01198; Zopiclone.
DR TCDB; 9.A.24.1.1; the mitochondrial outer membrane insertion pathway (mom-ip) family.
DR DMDM; 464399; -.
DR PaxDb; P30536; -.
DR PRIDE; P30536; -.
DR DNASU; 706; -.
DR Ensembl; ENST00000329563; ENSP00000328973; ENSG00000100300.
DR Ensembl; ENST00000337554; ENSP00000338004; ENSG00000100300.
DR GeneID; 706; -.
DR KEGG; hsa:706; -.
DR UCSC; uc003bdn.4; human.
DR CTD; 706; -.
DR GeneCards; GC22P043547; -.
DR HGNC; HGNC:1158; TSPO.
DR HPA; CAB011232; -.
DR MIM; 109610; gene.
DR neXtProt; NX_P30536; -.
DR PharmGKB; PA25473; -.
DR eggNOG; COG3476; -.
DR HOGENOM; HOG000224659; -.
DR InParanoid; P30536; -.
DR KO; K05770; -.
DR OMA; ATTLNYC; -.
DR OrthoDB; EOG7V7687; -.
DR PhylomeDB; P30536; -.
DR ChiTaRS; TSPO; human.
DR GeneWiki; Translocator_protein; -.
DR GenomeRNAi; 706; -.
DR NextBio; 2874; -.
DR PRO; PR:P30536; -.
DR ArrayExpress; P30536; -.
DR Bgee; P30536; -.
DR CleanEx; HS_TSPO; -.
DR Genevestigator; P30536; -.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0005741; C:mitochondrial outer membrane; NAS:ProtInc.
DR GO; GO:0005497; F:androgen binding; IEA:Ensembl.
DR GO; GO:0008503; F:benzodiazepine receptor activity; TAS:ProtInc.
DR GO; GO:0015485; F:cholesterol binding; TAS:HGNC.
DR GO; GO:0030325; P:adrenal gland development; IEA:Ensembl.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0006820; P:anion transport; TAS:HGNC.
DR GO; GO:0006915; P:apoptotic process; TAS:HGNC.
DR GO; GO:0048266; P:behavioral response to pain; IEA:Ensembl.
DR GO; GO:0008283; P:cell proliferation; TAS:HGNC.
DR GO; GO:0071476; P:cellular hypotonic response; IEA:Ensembl.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0071294; P:cellular response to zinc ion; IEA:Ensembl.
DR GO; GO:0060242; P:contact inhibition; IEA:Ensembl.
DR GO; GO:0008347; P:glial cell migration; IEA:Ensembl.
DR GO; GO:0006783; P:heme biosynthetic process; TAS:HGNC.
DR GO; GO:0060253; P:negative regulation of glial cell proliferation; IEA:Ensembl.
DR GO; GO:0045019; P:negative regulation of nitric oxide biosynthetic process; IEA:Ensembl.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IEA:Ensembl.
DR GO; GO:0014012; P:peripheral nervous system axon regeneration; IEA:Ensembl.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0051928; P:positive regulation of calcium ion transport; IEA:Ensembl.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; IEA:Ensembl.
DR GO; GO:0051901; P:positive regulation of mitochondrial depolarization; IEA:Ensembl.
DR GO; GO:0010940; P:positive regulation of necrotic cell death; IEA:Ensembl.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IEA:Ensembl.
DR GO; GO:0006626; P:protein targeting to mitochondrion; TAS:ProtInc.
DR GO; GO:0032374; P:regulation of cholesterol transport; TAS:HGNC.
DR GO; GO:0050810; P:regulation of steroid biosynthetic process; IEA:Ensembl.
DR GO; GO:0042493; P:response to drug; IEA:Ensembl.
DR GO; GO:0010042; P:response to manganese ion; IEA:Ensembl.
DR GO; GO:0032570; P:response to progesterone stimulus; IEA:Ensembl.
DR GO; GO:0033574; P:response to testosterone stimulus; IEA:Ensembl.
DR GO; GO:0010266; P:response to vitamin B1; IEA:Ensembl.
DR GO; GO:0006694; P:steroid biosynthetic process; IEA:Ensembl.
DR GO; GO:0008202; P:steroid metabolic process; TAS:HGNC.
DR InterPro; IPR004307; TspO_MBR.
DR PANTHER; PTHR10057; PTHR10057; 1.
DR Pfam; PF03073; TspO_MBR; 1.
DR PIRSF; PIRSF005859; PBR; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Membrane; Mitochondrion;
KW Polymorphism; Receptor; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1 169 Translocator protein.
FT /FTId=PRO_0000190997.
FT TRANSMEM 6 26 Helical; Name=1; (Potential).
FT TRANSMEM 47 67 Helical; Name=2; (Potential).
FT TRANSMEM 80 100 Helical; Name=3; (Potential).
FT TRANSMEM 106 126 Helical; Name=4; (Potential).
FT TRANSMEM 135 155 Helical; Name=5; (Potential).
FT VARIANT 147 147 T -> A (in dbSNP:rs6971).
FT /FTId=VAR_013617.
FT VARIANT 162 162 R -> H (in dbSNP:rs6972).
FT /FTId=VAR_013618.
FT VARIANT 169 169 E -> Q (in dbSNP:rs9333342).
FT /FTId=VAR_018868.
SQ SEQUENCE 169 AA; 18828 MW; 6DD741BF99AB89D9 CRC64;
MAPPWVPAMG FTLAPSLGCF VGSRFVHGEG LRWYAGLQKP SWHPPHWVLG PVWGTLYSAM
GYGSYLVWKE LGGFTEKAVV PLGLYTGQLA LNWAWPPIFF GARQMGWALV DLLLVSGAAA
ATTVAWYQVS PLAARLLYPY LAWLAFTTTL NYCVWRDNHG WRGGRRLPE
//
ID TSPOA_HUMAN Reviewed; 169 AA.
AC P30536; Q53Y59; Q6ICF9; Q96TF6;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 30-NOV-2010, sequence version 3.
DT 22-JAN-2014, entry version 124.
DE RecName: Full=Translocator protein;
DE AltName: Full=Mitochondrial benzodiazepine receptor;
DE AltName: Full=PKBS;
DE AltName: Full=Peripheral-type benzodiazepine receptor;
DE Short=PBR;
GN Name=TSPO; Synonyms=BZRP, MBR;
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 1), AND VARIANTS ALA-147 AND
RP HIS-162.
RX PubMed=1847678; DOI=10.1111/j.1432-1033.1991.tb15707.x;
RA Riond J., Mattei M.-G., Kaghad M., Dumont X., Guillemot J.-C.,
RA le Fur G., Caput D., Ferrara P.;
RT "Molecular cloning and chromosomal localization of a human peripheral-
RT type benzodiazepine receptor.";
RL Eur. J. Biochem. 195:305-311(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7721091; DOI=10.1016/0378-1119(94)00817-C;
RA Yakovlev A.G., Ruffo M., Jurka J., Krueger K.E.;
RT "Comparison of repetitive elements in the third intron of human and
RT rodent mitochondrial benzodiazepine receptor-encoding genes.";
RL Gene 155:201-205(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=16189298; DOI=10.1124/mol.105.015289;
RA Costa B., Salvetti A., Rossi L., Spinetti F., Lena A., Chelli B.,
RA Rechichi M., Da Pozzo E., Gremigni V., Martini C.;
RT "Peripheral benzodiazepine receptor: characterization in human T-
RT lymphoma Jurkat cells.";
RL Mol. Pharmacol. 69:37-44(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS
RP ALA-147 AND HIS-162.
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS
RP ALA-147 AND HIS-162.
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ALA-147 AND GLN-169.
RG NIEHS SNPs program;
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M.,
RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K.,
RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J.,
RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G.,
RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R.,
RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E.,
RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G.,
RA Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S.,
RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A.,
RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M.,
RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T.,
RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J.,
RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T.,
RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T.,
RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L.,
RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M.,
RA Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J.,
RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S.,
RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T.,
RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I.,
RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H.,
RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L.,
RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z.,
RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P.,
RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S.,
RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J.,
RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T.,
RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J.,
RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S.,
RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E.,
RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P.,
RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E.,
RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X.,
RA Khan A.S., Lane L., Tilahun Y., Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph;
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 [9]
RP INTERACTION WITH BZRAP1.
RC TISSUE=Brain;
RX PubMed=9915832; DOI=10.1074/jbc.274.5.2938;
RA Galiegue S., Jbilo O., Combes T., Bribes E., Carayon P., Le Fur G.,
RA Casellas P.;
RT "Cloning and characterization of PRAX-1. A new protein that
RT specifically interacts with the peripheral benzodiazepine receptor.";
RL J. Biol. Chem. 274:2938-2952(1999).
RN [10]
RP NOMENCLATURE.
RX PubMed=16822554; DOI=10.1016/j.tips.2006.06.005;
RA Papadopoulos V., Baraldi M., Guilarte T.R., Knudsen T.B.,
RA Lacapere J.-J., Lindemann P., Norenberg M.D., Nutt D., Weizman A.,
RA Zhang M.-R., Gavish M.;
RT "Translocator protein (18kDa): new nomenclature for the peripheral-
RT type benzodiazepine receptor based on its structure and molecular
RT function.";
RL Trends Pharmacol. Sci. 27:402-409(2006).
RN [11]
RP INTERACTION WITH MOST-1.
RX PubMed=17143515;
RA Tan J.M.M., Chow V.T.K.;
RT "Cellular expression, localization and interactions of the product of
RT the human MOST-1 gene associated with breast and prostate cancers.";
RL Int. J. Oncol. 30:81-89(2007).
RN [12]
RP TISSUE SPECIFICITY.
RX PubMed=20600583; DOI=10.1016/j.mce.2010.06.013;
RA Batarseh A., Papadopoulos V.;
RT "Regulation of translocator protein 18 kDa (TSPO) expression in health
RT and disease states.";
RL Mol. Cell. Endocrinol. 327:1-12(2010).
RN [13]
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 [14]
RP VARIANTS ALA-147 AND HIS-162.
RX PubMed=11215759; DOI=10.1007/s007020070090;
RA Kurumaji A., Nomoto H., Yoshikawa T., Okubo Y., Toru M.;
RT "An association study between two missense variations of the
RT benzodiazepine receptor (peripheral) gene and schizophrenia in a
RT Japanese sample.";
RL J. Neural Transm. 107:491-500(2000).
RN [15]
RP VARIANTS ALA-147 AND HIS-162.
RX PubMed=11304832; DOI=10.1002/ajmg.1194;
RA Kurumaji A., Nomoto H., Yamada K., Yoshikawa T., Toru M.;
RT "No association of two missense variations of the benzodiazepine
RT receptor (peripheral) gene and mood disorders in a Japanese sample.";
RL Am. J. Med. Genet. 105:172-175(2001).
CC -!- FUNCTION: Responsible for the manifestation of peripheral-type
CC benzodiazepine recognition sites and is most likely to comprise
CC binding domains for benzodiazepines and isoquinoline carboxamides.
CC May play a role in the transport of porphyrins and heme. Plays a
CC role in the transport of cholesterol across mitochondrial
CC membranes in steroidogenic cells (By similarity).
CC -!- SUBUNIT: Interacts with BZRAP1 (By similarity). May interact with
CC STAR (By similarity). Interacts with MOST-1.
CC -!- SUBCELLULAR LOCATION: Mitochondrion membrane; Multi-pass membrane
CC protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P30536-1; Sequence=Displayed;
CC Name=2; Synonyms=PBR-S;
CC IsoId=B1AH88-1; Sequence=External;
CC Note=No experimental confirmation available. The relatively low
CC levels of the corresponding mRNA suggest that it might represent
CC errors of the splicing machinery. In addition, isoform 2 is
CC derived from a different reading frame, compared to isoform 1
CC and lacks homolog support;
CC -!- TISSUE SPECIFICITY: Found in many tissue types. Expressed at the
CC highest levels under normal conditions in tissues that synthesize
CC steroids.
CC -!- SIMILARITY: Belongs to the TspO/BZRP family.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/bzrp/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; M36035; AAA03652.1; -; mRNA.
DR EMBL; U12421; AAA83252.1; -; Genomic_DNA.
DR EMBL; AY998017; AAY45787.1; -; mRNA.
DR EMBL; BT006949; AAP35595.1; -; mRNA.
DR EMBL; CR456409; CAG30295.1; -; mRNA.
DR EMBL; AY383615; AAQ75703.1; -; Genomic_DNA.
DR EMBL; Z82214; CAB55884.1; -; Genomic_DNA.
DR EMBL; BC001110; AAH01110.1; -; mRNA.
DR PIR; I38724; I38724.
DR PIR; JE0149; JE0149.
DR PIR; S14257; S14257.
DR RefSeq; NP_000705.2; NM_000714.5.
DR RefSeq; NP_001243459.1; NM_001256530.1.
DR RefSeq; NP_001243460.1; NM_001256531.1.
DR UniGene; Hs.202; -.
DR ProteinModelPortal; P30536; -.
DR BindingDB; P30536; -.
DR ChEMBL; CHEMBL5742; -.
DR DrugBank; DB00546; Adinazolam.
DR DrugBank; DB00404; Alprazolam.
DR DrugBank; DB01178; Chlormezanone.
DR DrugBank; DB01594; Cinolazepam.
DR DrugBank; DB01068; Clonazepam.
DR DrugBank; DB00628; Clorazepate.
DR DrugBank; DB01559; Clotiazepam.
DR DrugBank; DB00829; Diazepam.
DR DrugBank; DB00822; Disulfiram.
DR DrugBank; DB01215; Estazolam.
DR DrugBank; DB00402; Eszopiclone.
DR DrugBank; DB01544; Flunitrazepam.
DR DrugBank; DB00801; Halazepam.
DR DrugBank; DB00186; Lorazepam.
DR DrugBank; DB00231; Temazepam.
DR DrugBank; DB00897; Triazolam.
DR DrugBank; DB00962; Zaleplon.
DR DrugBank; DB00425; Zolpidem.
DR DrugBank; DB01198; Zopiclone.
DR TCDB; 9.A.24.1.1; the mitochondrial outer membrane insertion pathway (mom-ip) family.
DR DMDM; 464399; -.
DR PaxDb; P30536; -.
DR PRIDE; P30536; -.
DR DNASU; 706; -.
DR Ensembl; ENST00000329563; ENSP00000328973; ENSG00000100300.
DR Ensembl; ENST00000337554; ENSP00000338004; ENSG00000100300.
DR GeneID; 706; -.
DR KEGG; hsa:706; -.
DR UCSC; uc003bdn.4; human.
DR CTD; 706; -.
DR GeneCards; GC22P043547; -.
DR HGNC; HGNC:1158; TSPO.
DR HPA; CAB011232; -.
DR MIM; 109610; gene.
DR neXtProt; NX_P30536; -.
DR PharmGKB; PA25473; -.
DR eggNOG; COG3476; -.
DR HOGENOM; HOG000224659; -.
DR InParanoid; P30536; -.
DR KO; K05770; -.
DR OMA; ATTLNYC; -.
DR OrthoDB; EOG7V7687; -.
DR PhylomeDB; P30536; -.
DR ChiTaRS; TSPO; human.
DR GeneWiki; Translocator_protein; -.
DR GenomeRNAi; 706; -.
DR NextBio; 2874; -.
DR PRO; PR:P30536; -.
DR ArrayExpress; P30536; -.
DR Bgee; P30536; -.
DR CleanEx; HS_TSPO; -.
DR Genevestigator; P30536; -.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0005741; C:mitochondrial outer membrane; NAS:ProtInc.
DR GO; GO:0005497; F:androgen binding; IEA:Ensembl.
DR GO; GO:0008503; F:benzodiazepine receptor activity; TAS:ProtInc.
DR GO; GO:0015485; F:cholesterol binding; TAS:HGNC.
DR GO; GO:0030325; P:adrenal gland development; IEA:Ensembl.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0006820; P:anion transport; TAS:HGNC.
DR GO; GO:0006915; P:apoptotic process; TAS:HGNC.
DR GO; GO:0048266; P:behavioral response to pain; IEA:Ensembl.
DR GO; GO:0008283; P:cell proliferation; TAS:HGNC.
DR GO; GO:0071476; P:cellular hypotonic response; IEA:Ensembl.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0071294; P:cellular response to zinc ion; IEA:Ensembl.
DR GO; GO:0060242; P:contact inhibition; IEA:Ensembl.
DR GO; GO:0008347; P:glial cell migration; IEA:Ensembl.
DR GO; GO:0006783; P:heme biosynthetic process; TAS:HGNC.
DR GO; GO:0060253; P:negative regulation of glial cell proliferation; IEA:Ensembl.
DR GO; GO:0045019; P:negative regulation of nitric oxide biosynthetic process; IEA:Ensembl.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IEA:Ensembl.
DR GO; GO:0014012; P:peripheral nervous system axon regeneration; IEA:Ensembl.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0051928; P:positive regulation of calcium ion transport; IEA:Ensembl.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; IEA:Ensembl.
DR GO; GO:0051901; P:positive regulation of mitochondrial depolarization; IEA:Ensembl.
DR GO; GO:0010940; P:positive regulation of necrotic cell death; IEA:Ensembl.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IEA:Ensembl.
DR GO; GO:0006626; P:protein targeting to mitochondrion; TAS:ProtInc.
DR GO; GO:0032374; P:regulation of cholesterol transport; TAS:HGNC.
DR GO; GO:0050810; P:regulation of steroid biosynthetic process; IEA:Ensembl.
DR GO; GO:0042493; P:response to drug; IEA:Ensembl.
DR GO; GO:0010042; P:response to manganese ion; IEA:Ensembl.
DR GO; GO:0032570; P:response to progesterone stimulus; IEA:Ensembl.
DR GO; GO:0033574; P:response to testosterone stimulus; IEA:Ensembl.
DR GO; GO:0010266; P:response to vitamin B1; IEA:Ensembl.
DR GO; GO:0006694; P:steroid biosynthetic process; IEA:Ensembl.
DR GO; GO:0008202; P:steroid metabolic process; TAS:HGNC.
DR InterPro; IPR004307; TspO_MBR.
DR PANTHER; PTHR10057; PTHR10057; 1.
DR Pfam; PF03073; TspO_MBR; 1.
DR PIRSF; PIRSF005859; PBR; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Membrane; Mitochondrion;
KW Polymorphism; Receptor; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1 169 Translocator protein.
FT /FTId=PRO_0000190997.
FT TRANSMEM 6 26 Helical; Name=1; (Potential).
FT TRANSMEM 47 67 Helical; Name=2; (Potential).
FT TRANSMEM 80 100 Helical; Name=3; (Potential).
FT TRANSMEM 106 126 Helical; Name=4; (Potential).
FT TRANSMEM 135 155 Helical; Name=5; (Potential).
FT VARIANT 147 147 T -> A (in dbSNP:rs6971).
FT /FTId=VAR_013617.
FT VARIANT 162 162 R -> H (in dbSNP:rs6972).
FT /FTId=VAR_013618.
FT VARIANT 169 169 E -> Q (in dbSNP:rs9333342).
FT /FTId=VAR_018868.
SQ SEQUENCE 169 AA; 18828 MW; 6DD741BF99AB89D9 CRC64;
MAPPWVPAMG FTLAPSLGCF VGSRFVHGEG LRWYAGLQKP SWHPPHWVLG PVWGTLYSAM
GYGSYLVWKE LGGFTEKAVV PLGLYTGQLA LNWAWPPIFF GARQMGWALV DLLLVSGAAA
ATTVAWYQVS PLAARLLYPY LAWLAFTTTL NYCVWRDNHG WRGGRRLPE
//
MIM
109610
*RECORD*
*FIELD* NO
109610
*FIELD* TI
*109610 TRANSLOCATOR PROTEIN, 18-KD; TSPO
;;BENZODIAZEPINE RECEPTOR, PERIPHERAL; BZRP; PBR;;
read moreBENZODIAZEPINE PERIPHERAL BINDING SITE; PBS; BPBS;;
ISOQUINOLINE CARBOXAMIDE-BINDING PROTEIN
*FIELD* TX
DESCRIPTION
TSPO has channel-like properties and is primarily located in the outer
mitochondrial membrane. It is involved in a variety of functions,
including immunologic responses, apoptosis, and steroidogenesis. The
proapoptotic function of TSPO appears to involve modulation of the
mitochondrial transition pore (MPTP), a channel formed by the
voltage-dependent anion channel (VDAC; see 604492) and the adenine
nucleotide transporter (ANT; see 103220). In steroidogenesis, TSPO
appears to operate as a translocator to transfer cholesterol into
mitochondria, where it is converted to pregnenolone (review by Veenman
et al., 2007).
CLONING
Benzodiazepines are psychoactive drugs with sedative, anxiolytic, and
anticonvulsant properties. They exert these actions through receptors
located in the central nervous system; however, some benzodiazepines
also interact with a different type of receptor present mainly in the
mitochondrial compartment of peripheral tissues. Riond et al. (1991)
found that the peripheral receptor is similar in rat, Chinese hamster,
and human. Based on these results, they screened a human cDNA library
with oligonucleotide probes derived from the Chinese hamster sequence.
One clone contained a full-length representation of human peripheral
binding site (PBS) mRNA. The amino acid sequence of human benzodiazepine
PBS deduced from the cDNA was 79% identical to that of rat Pbs.
GENE FUNCTION
Chang et al. (1992) found that the benzodiazepine receptor expressed in
COS-1 cells had remarkably different affinities than did the endogenous
human benzodiazepine receptor. They interpreted this finding as
indicating that the host cell and/or posttranslational modification had
important influences on function of the receptor protein.
Shoukrun et al. (2008) found that knockdown of TSPO with antisense TSPO
or small interfering RNA in HT29 human colorectal cancer cells increased
the rate of cell proliferation compared with controls and reduced the
rate of apoptosis. In contrast, pharmacologic activation of TSPO reduced
the tumorigenicity of HT29 xenografts in immunodeficient mice and
increased their rate of survival. Shoukrun et al. (2008) noted that
their results confirmed previous findings in mouse and rat, and they
concluded that TSPO is a proapoptotic factor.
- Reviews
Veenman et al. (2007) reviewed the roles of TSPO in immunologic
responses, apoptosis, and steroidogenesis. They suggested that the
involvement of TSPO in such disparate biologic functions may indicate a
multidimensional role for TSPO in the host-defense response to disease
and injury.
GENE STRUCTURE
Using a cloned human PBR cDNA as probe, Lin et al. (1993) cloned the
gene, which they found covers 13 kb and is divided into 4 exons, with
exon 1 encoding only a short 5-prime untranslated segment.
MAPPING
Using the cDNA of human BZRP as a probe, Riond et al. (1991) localized
the BSRP gene to chromosome 22q13.3 by in situ hybridization. Chang et
al. (1992) mapped the BZRP gene to chromosome 22 by hybridization to DNA
from a somatic cell hybrid mapping panel. With a regional panel for
chromosome 22, they localized the gene within band 22q13.31.
Bucan et al. (1993) mapped the mouse Bzrp gene to chromosome 15.
*FIELD* RF
1. Bucan, M.; Gatalica, B.; Nolan, P.; Chung, A.; Leroux, A.; Grossman,
M. H.; Nadeau, J. H.; Emanuel, B. S.; Budarf, M.: Comparative mapping
of 9 human chromosome 22q loci in the laboratory mouse. Hum. Molec.
Genet. 2: 1245-1252, 1993.
2. Chang, Y. J.; McCabe, R. T.; Rennert, H.; Budarf, M. L.; Sayegh,
R.; Emanuel, B. S.; Skolnick, P.; Strauss, J. F., III: The human
'peripheral-type' benzodiazepine receptor: regional mapping of the
gene and characterization of the receptor expressed from cDNA. DNA
Cell Biol. 11: 471-480, 1992.
3. Lin, D.; Chang, Y. J.; Strauss, J. F., III; Miller, W. L.: The
human peripheral benzodiazepine receptor gene: cloning and characterization
of alternative splicing in normal tissues and in a patient with congenital
lipoid adrenal hyperplasia. Genomics 18: 643-650, 1993.
4. Riond, J.; Mattei, M. G.; Kaghad, M.; Dumont, X.; Guillemot, J.
C.; Le Fur, G.; Caput, D.; Ferrara, P.: Molecular cloning and chromosomal
localization of a human peripheral-type benzodiazepine receptor. Europ.
J. Biochem. 195: 305-311, 1991.
5. Shoukrun, R.; Veenman, L.; Shandalov, Y.; Leschiner, S.; Spanier,
I.; Karry, R.; Katz, Y.; Weisinger, G.; Weizman, A.; Gavish, M.:
The 18-kDa translocator protein, formerly known as the peripheral-type
benzodiazepine receptor, confers proapoptotic and antineoplastic effects
in a human colorectal cancer cell line. Pharmacogenet. Genomics 18:
977-988, 2008.
6. Veenman, L.; Papadopoulos, V.; Gavish, M.: Channel-like functions
of the 18-kDa translocator protein (TSPO): regulation of apoptosis
and steroidogenesis as part of the host-defense response. Curr. Pharm.
Des. 13: 2385-2405, 2007.
*FIELD* CN
Patricia A. Hartz - updated: 05/12/2010
Matthew B. Gross - updated: 5/12/2010
*FIELD* CD
Victor A. McKusick: 6/25/1991
*FIELD* ED
mgross: 05/12/2010
mgross: 5/12/2010
mimadm: 4/26/1994
carol: 2/2/1994
carol: 9/20/1993
carol: 11/3/1992
supermim: 3/16/1992
carol: 1/29/1992
*RECORD*
*FIELD* NO
109610
*FIELD* TI
*109610 TRANSLOCATOR PROTEIN, 18-KD; TSPO
;;BENZODIAZEPINE RECEPTOR, PERIPHERAL; BZRP; PBR;;
read moreBENZODIAZEPINE PERIPHERAL BINDING SITE; PBS; BPBS;;
ISOQUINOLINE CARBOXAMIDE-BINDING PROTEIN
*FIELD* TX
DESCRIPTION
TSPO has channel-like properties and is primarily located in the outer
mitochondrial membrane. It is involved in a variety of functions,
including immunologic responses, apoptosis, and steroidogenesis. The
proapoptotic function of TSPO appears to involve modulation of the
mitochondrial transition pore (MPTP), a channel formed by the
voltage-dependent anion channel (VDAC; see 604492) and the adenine
nucleotide transporter (ANT; see 103220). In steroidogenesis, TSPO
appears to operate as a translocator to transfer cholesterol into
mitochondria, where it is converted to pregnenolone (review by Veenman
et al., 2007).
CLONING
Benzodiazepines are psychoactive drugs with sedative, anxiolytic, and
anticonvulsant properties. They exert these actions through receptors
located in the central nervous system; however, some benzodiazepines
also interact with a different type of receptor present mainly in the
mitochondrial compartment of peripheral tissues. Riond et al. (1991)
found that the peripheral receptor is similar in rat, Chinese hamster,
and human. Based on these results, they screened a human cDNA library
with oligonucleotide probes derived from the Chinese hamster sequence.
One clone contained a full-length representation of human peripheral
binding site (PBS) mRNA. The amino acid sequence of human benzodiazepine
PBS deduced from the cDNA was 79% identical to that of rat Pbs.
GENE FUNCTION
Chang et al. (1992) found that the benzodiazepine receptor expressed in
COS-1 cells had remarkably different affinities than did the endogenous
human benzodiazepine receptor. They interpreted this finding as
indicating that the host cell and/or posttranslational modification had
important influences on function of the receptor protein.
Shoukrun et al. (2008) found that knockdown of TSPO with antisense TSPO
or small interfering RNA in HT29 human colorectal cancer cells increased
the rate of cell proliferation compared with controls and reduced the
rate of apoptosis. In contrast, pharmacologic activation of TSPO reduced
the tumorigenicity of HT29 xenografts in immunodeficient mice and
increased their rate of survival. Shoukrun et al. (2008) noted that
their results confirmed previous findings in mouse and rat, and they
concluded that TSPO is a proapoptotic factor.
- Reviews
Veenman et al. (2007) reviewed the roles of TSPO in immunologic
responses, apoptosis, and steroidogenesis. They suggested that the
involvement of TSPO in such disparate biologic functions may indicate a
multidimensional role for TSPO in the host-defense response to disease
and injury.
GENE STRUCTURE
Using a cloned human PBR cDNA as probe, Lin et al. (1993) cloned the
gene, which they found covers 13 kb and is divided into 4 exons, with
exon 1 encoding only a short 5-prime untranslated segment.
MAPPING
Using the cDNA of human BZRP as a probe, Riond et al. (1991) localized
the BSRP gene to chromosome 22q13.3 by in situ hybridization. Chang et
al. (1992) mapped the BZRP gene to chromosome 22 by hybridization to DNA
from a somatic cell hybrid mapping panel. With a regional panel for
chromosome 22, they localized the gene within band 22q13.31.
Bucan et al. (1993) mapped the mouse Bzrp gene to chromosome 15.
*FIELD* RF
1. Bucan, M.; Gatalica, B.; Nolan, P.; Chung, A.; Leroux, A.; Grossman,
M. H.; Nadeau, J. H.; Emanuel, B. S.; Budarf, M.: Comparative mapping
of 9 human chromosome 22q loci in the laboratory mouse. Hum. Molec.
Genet. 2: 1245-1252, 1993.
2. Chang, Y. J.; McCabe, R. T.; Rennert, H.; Budarf, M. L.; Sayegh,
R.; Emanuel, B. S.; Skolnick, P.; Strauss, J. F., III: The human
'peripheral-type' benzodiazepine receptor: regional mapping of the
gene and characterization of the receptor expressed from cDNA. DNA
Cell Biol. 11: 471-480, 1992.
3. Lin, D.; Chang, Y. J.; Strauss, J. F., III; Miller, W. L.: The
human peripheral benzodiazepine receptor gene: cloning and characterization
of alternative splicing in normal tissues and in a patient with congenital
lipoid adrenal hyperplasia. Genomics 18: 643-650, 1993.
4. Riond, J.; Mattei, M. G.; Kaghad, M.; Dumont, X.; Guillemot, J.
C.; Le Fur, G.; Caput, D.; Ferrara, P.: Molecular cloning and chromosomal
localization of a human peripheral-type benzodiazepine receptor. Europ.
J. Biochem. 195: 305-311, 1991.
5. Shoukrun, R.; Veenman, L.; Shandalov, Y.; Leschiner, S.; Spanier,
I.; Karry, R.; Katz, Y.; Weisinger, G.; Weizman, A.; Gavish, M.:
The 18-kDa translocator protein, formerly known as the peripheral-type
benzodiazepine receptor, confers proapoptotic and antineoplastic effects
in a human colorectal cancer cell line. Pharmacogenet. Genomics 18:
977-988, 2008.
6. Veenman, L.; Papadopoulos, V.; Gavish, M.: Channel-like functions
of the 18-kDa translocator protein (TSPO): regulation of apoptosis
and steroidogenesis as part of the host-defense response. Curr. Pharm.
Des. 13: 2385-2405, 2007.
*FIELD* CN
Patricia A. Hartz - updated: 05/12/2010
Matthew B. Gross - updated: 5/12/2010
*FIELD* CD
Victor A. McKusick: 6/25/1991
*FIELD* ED
mgross: 05/12/2010
mgross: 5/12/2010
mimadm: 4/26/1994
carol: 2/2/1994
carol: 9/20/1993
carol: 11/3/1992
supermim: 3/16/1992
carol: 1/29/1992