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9.A.24.1.1
The peripheral benzodiazepine receptor (PBR or TSPO1) can bind isoquinoline carboxamides (Riond et al. 1991) and integrates into the mitochondrial outer membrane (MOM) through five hydrophobic TMSs. The protein has 7 TMSs in a probable 2 + 1 + 4 TMS arrangement. It is a mitochondrial cholesterol and porphyrin uptake transporter (Jaremko et al. 2014; Taylor et al. 2014) but is also part of the mitochondrial permeability transition pore (MPTP) which includes cyclophilin D, VDAC (TC#1.B.8) and the adenine nucleotide translocator (Austin et al. 2013).  The 3-d structure has been determined at 2.4 Å resolution bound to its high affinity ligand, PK11195 which causes the otherwise loose 5 helix bundle to form a tight bundle with a hydrophobic pocket for PK11195 (Jaremko et al. 2014). It is upregulated in glial cells during neuroinflammation in Alzheimer's disease (Asih et al. 2022). The common A147T polymorphism compromises ligand binding and has been linked to increased risk of neuropsychiatric disorders, possibly by reducing TSPO protein stability. WT TSPO binds 30 partners, yet A147T TSPO binds only 23, one of which is 14-3-3 theta (YWHAQ) (TC# 8.A.98.1.9) (Asih et al. 2022).  Translocator protein 18 kDa (TSPO) is a promising molecular target for image-guided surgery of solid cancers (Wongso et al. 2024). It transports heme as well as cholesterol and porphorins.  TSPO deficiency is accompanied by reduced expression of the voltage-dependent anion channel (VDAC). A reduced TSPO and VDAC expression is observed in cells derived from patients suffering from major depressive disorder (MDD). The modulatory function of TSPO and the similar functional phenotype of cells derived from patients with depression, TSPO plays a rolein the etiology or pathology of MDD. Thus, a general impairment of mitochondrial function in TSPO knockout (KO) cells has multiple functions (Bader et al. 2024).

Accession Number:Q6ICF9
Protein Name:Translocator protein
Length:169
Molecular Weight:18828.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:4
Location1 / Topology2 / Orientation3: Mitochondrion membrane1 / Multi-pass membrane protein2
Substrate cholesterol, porphyrin

Cross database links:

Entrez Gene ID: 706   
Pfam: PF03073   
KEGG: hsa:706   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005741 C:mitochondrial outer membrane
GO:0005497 F:androgen binding
GO:0008503 F:benzodiazepine receptor activity
GO:0015485 F:cholesterol binding
GO:0030325 P:adrenal gland development
GO:0007568 P:aging
GO:0006820 P:anion transport
GO:0006915 P:apoptotic process
GO:0048266 P:behavioral response to pain
GO:0008283 P:cell proliferation
GO:0071476 P:cellular hypotonic response
GO:0071222 P:cellular response to lipopolysaccharide
GO:0071294 P:cellular response to zinc ion
GO:0060242 P:contact inhibition
GO:0008347 P:glial cell migration
GO:0006783 P:heme biosynthetic process
GO:0060253 P:negative regulation of glial cell proliferation
GO:0045019 P:negative regulation of nitric oxide biosynthetic process
GO:0032720 P:negative regulation of tumor necrosis factor production
GO:0014012 P:peripheral nervous system axon regeneration
GO:0043065 P:positive regulation of apoptotic process
GO:0051928 P:positive regulation of calcium ion transport
GO:0060252 P:positive regulation of glial cell proliferation
GO:0051901 P:positive regulation of mitochondrial depolarization
GO:0010940 P:positive regulation of necrotic cell death
GO:2000379 P:positive regulation of reactive oxygen species metabolic process
GO:0006626 P:protein targeting to mitochondrion
GO:0032374 P:regulation of cholesterol transport
GO:0050810 P:regulation of steroid biosynthetic process
GO:0042493 P:response to drug
GO:0010042 P:response to manganese ion
GO:0032570 P:response to progesterone stimulus
GO:0033574 P:response to testosterone stimulus
GO:0010266 P:response to vitamin B1
GO:0006694 P:steroid biosynthetic process
GO:0008202 P:steroid metabolic process

References (12)

[1] “Molecular cloning and chromosomal localization of a human peripheral-type benzodiazepine receptor.”  Riond J.et.al.   1847678
[2] “Comparison of repetitive elements in the third intron of human and rodent mitochondrial benzodiazepine receptor-encoding genes.”  Yakovlev A.G.et.al.   7721091
[3] “Peripheral benzodiazepine receptor: characterization in human T-lymphoma Jurkat cells.”  Costa B.et.al.   16189298
[4] “A genome annotation-driven approach to cloning the human ORFeome.”  Collins J.E.et.al.   15461802
[5] “The DNA sequence of human chromosome 22.”  Dunham I.et.al.   10591208
[6] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[7] “Cloning and characterization of PRAX-1. A new protein that specifically interacts with the peripheral benzodiazepine receptor.”  Galiegue S.et.al.   9915832
[8] “Translocator protein (18kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function.”  Papadopoulos V.et.al.   16822554
[9] “Cellular expression, localization and interactions of the product of the human MOST-1 gene associated with breast and prostate cancers.”  Tan J.M.M.et.al.   17143515
[10] “Regulation of translocator protein 18 kDa (TSPO) expression in health and disease states.”  Batarseh A.et.al.   20600583
[11] “An association study between two missense variations of the benzodiazepine receptor (peripheral) gene and schizophrenia in a Japanese sample.”  Kurumaji A.et.al.   11215759
[12] “No association of two missense variations of the benzodiazepine receptor (peripheral) gene and mood disorders in a Japanese sample.”  Kurumaji A.et.al.   11304832

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FASTA formatted sequence 
1:	MAPPWVPAMG FTLAPSLGCF VGSRFVHGEG LRWYAGLQKP SWHPPHWVLG PVWGTLYSAM 
61:	GYGSYLVWKE LGGFTEKAVV PLGLYTGQLA LNWAWPPIFF GARQMGWALV DLLLVSGAAA 
121:	ATTVAWYQVS PLAARLLYPY LAWLAFTTTL NYCVWRDNHG WRGGRRLPE