Translocator protein (TSPO)
The protein contains 169 amino acids for an estimated molecular weight of 18828 Da.
Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Promotes the transport of cholesterol across mitochondrial membranes and may play a role in lipid metabolism (PubMed:24814875), but its precise physiological role is controversial. It is apparently not required for steroid hormone biosynthesis. Was initially identified as peripheral-type benzodiazepine receptor; can also bind isoquinoline carboxamides (PubMed:1847678). (updated: Oct. 10, 2018)
Protein identification was indicated in the following studies:
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is predicted to be membranous by TOPCONS.
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Biological Process
Adrenal gland development
Aging
Anion transport
Apoptotic process
Behavioral response to pain
C21-steroid hormone biosynthetic process
Cell population proliferation
Cellular hypotonic response
Cellular response to lipopolysaccharide
Cellular response to zinc ion
Chloride transport
Contact inhibition
Glial cell migration
Heme biosynthetic process
Lipid transport
Maintenance of protein location in mitochondrion
Negative regulation of ATP metabolic process
Negative regulation of autophagy of mitochondrion
Negative regulation of glial cell proliferation
Negative regulation of nitric oxide biosynthetic process
Negative regulation of protein ubiquitination
Negative regulation of tumor necrosis factor production
Peripheral nervous system axon regeneration
Positive regulation of apoptotic process
Positive regulation of calcium ion transport
Positive regulation of glial cell proliferation
Positive regulation of mitochondrial depolarization
Positive regulation of necrotic cell death
Positive regulation of reactive oxygen species metabolic process
Protein targeting to mitochondrion
Regulation of cell population proliferation
Regulation of cholesterol transport
Regulation of steroid biosynthetic process
Response to drug
Response to manganese ion
Response to progesterone
Response to testosterone
Response to vitamin B1
Steroid metabolic process
The reference OMIM entry for this protein is 109610
Translocator protein, 18-kd; tspo
Benzodiazepine receptor, peripheral; bzrp; pbr
Benzodiazepine peripheral binding site; pbs; bpbs
Isoquinoline carboxamide-binding protein
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.BIOCHEMICAL FEATURES
- 3-Dimensional Structure Jaremko et al. (2014) presented the 3-dimensional high-resolution structure of mammalian TSPO reconstituted in detergent micelles in complex with its high-affinity ligand PK11195. The TSPO-PK11195 structure is described by a tight bundle of 5 transmembrane alpha-helices that form a hydrophobic pocket accepting PK11195. Ligand-induced stabilization of the structure of TSPO suggested a molecular mechanism for the stimulation of cholesterol transport into mitochondria.MAPPING
Using the cDNA of human BZRP as a probe, Riond et al. (1991) localized the BSRP gene to chromosome 22q1 ... More on the omim web site
Feb. 23, 2019: Protein entry updated
Automatic update: comparative model was added.
Feb. 23, 2019: Protein entry updated
Automatic update: model status changed
Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 109610 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).