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TCID	Name	Domain	Kingdom/Phylum	Protein(s)
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).	Eukaryota	Metazoa, Chordata	PBR of Homo sapiens (Q6ICF9)
9.A.24.1.2	The outer membrane tryptophan-rich sensory protein (TspO) of the TSPO/MBR family of 159 aas and 5 TMSs (Yeliseev et al. 1997; Yeliseev and Kaplan 1999). The 10 Å cryo electron microscopy structure is known (Korkhov et al. 2010) as are 1.8, 2.4 and 2.5 Å structures solved by x-ray crystallography (Li et al. 2015). Crystals obtained in the lipidic cubic phase reveal the binding site of an endogenous porphyrin ligand. The three crystal structures reveal a dimer, providing insights into the controversial physiological role of TSPO and how a mutation in the human homologue causes psychiatric disorders and reduced pregnenolone production (Li et al. 2015).	Bacteria	Pseudomonadota	TspO of Rhodobacter spheroides
9.A.24.1.3	The Endoplasmic reticulum/Golgi TSPO protein is mainly detected in dry seeds, but can be induced in vegetative tissues by osmotic or salt stress or abscisic acid (ABA) treatment (Guillaumot et al. 2009).	Eukaryota	Viridiplantae, Streptophyta	TSPO of Arabidopsis thaliana
9.A.24.1.4	Tryptophan-rich sensory protein homologue, TspO, of 158 aas and 5 TMSs	Bacteria	Cyanobacteriota	TspO of Nostoc sp.
9.A.24.1.5	TspO/MBR family protein of 186 aas and 5 TMSs	Eukaryota	Discosea	TspO/MBR family protein of Acanthamoeba castellanii
9.A.24.1.6	TspO/MBR family protein of 186 aas and 5 TMSs	Bacteria	Bacteroidota	TspO of Niastella koreensis
9.A.24.1.7	TspO of 159 aas and 5 TM	Bacteria	Bacillota	TspO of Lactococcus lactis
9.A.24.1.8	Peripheral-type benzodiazepine receptor of 188 aas and 4 or 5 TMSs.	Eukaryota	Viridiplantae, Streptophyta	Peripheral-type benzodiazepine receptor of Zea mays
9.A.24.1.9	TspO homologue of 193 aas and 4 or 5 TMSs.	Eukaryota	Viridiplantae, Streptophyta	TspO of Oryza sativa
9.A.24.1.10	Uncharacterized protein of 171 aas and 5 TMSs	Eukaryota	Metazoa, Nematoda	UP of Loa loa (Eye worm) (Filaria loa)
9.A.24.1.11	TspO protein of 141 aas and 4-5 TMSs	Viruses	Bamfordvirae, Nucleocytoviricota	TspO of Phaeocystis globosa virus
9.A.24.1.12	TspO-like; MBR-like protein of 163 aas and 4 TMSs in a 1 + 3 TMS arrangement.	Eukaryota	Rhodophyta	TspO-like protein of Galdieria sulfuraria
9.A.24.1.13	TspO/MBR family member of 151 aas and 5 TMSs. The crystal structure has been determined at 1.7 Å resolution (Guo et al. 2015). The protein was solved in complex with the benzodiazepine-like inhibitor, PK11195. TspO-mediated protoporphyrin IX (PpIX) reactions were also described, including catalytic degradation to a previously undescribed heme derivative. Structure-inspired mutations allowed the investigation of the reaction mechanisms, showing that TSPOs from Xenopus and man have similar PpIX-directed activities. Although TSPOs have been regarded as transporters, the catalytic activity in PpIX degradation suggests physiological importance for TSPOs in protection against oxidative stress (Guo et al. 2015).	Bacteria	Bacillota	TspO of Bacillus cereus
9.A.24.1.14	Uncharacterized protein of 134 aas and 4 TMSs (Hug et al. 2016).	Bacteria	Candidatus Peregrinibacteria	UP of Candidatus Peribacter riflensis
9.A.24.1.15	Uncharacterized protein of 161 aas and 4 TMSs.	Bacteria	Pseudomonadota	UP of Luteimonas mephitis
9.A.24.1.16	Tryptophan-rich sensory protein. TSPO, of 167 aas and 5 TMSs	Archaea	Euryarchaeota	TSPO of Halococcus sediminicola
9.A.24.1.17	TSPO2 of 170 aas and 5 TMSs in a 1 + 4 TMS arrangement. 5-Aminolevulinic acid (ALA) is the first precursor of heme biosynthesis pathway. The exogenous addition of ALA to cells leads to protoporphyrin IX (PPIX) accumulation. Several types of ALA transporters have been described depending on the cell type, but there was no clear entry pathway for erythroid cells. The 18 kDa translocator protein (TSPO) has been proposed to be involved in the transport of porphyrins and heme analogs, but ALA-induced PPIX accumulation in erythroleukemia cells (UT-7 and K562) was impaired by PK 11195, a competitive inhibitor of both transmembrane proteins TSPO (1 and 2). PK 11195 did not modify the activity of the enzymes of heme biosynthesis, suggesting that ALA entry at the plasma membrane is the limiting factor. In contrast, porphobilinogen (PBG)-induced PPIX accumulation was not affected by PK 11195, suggesting that plasma membrane TSPO2 is a selective transporter of ALA. Overexpression of TSPO2 at the plasma membrane of erythroleukemia cells increased ALA-induced PPIX accumulation, confirming the role of TSPO2 in the import of ALA into the cells. Thus, ALA-induced PPIX accumulation in erythroid cells involves TSPO2 as a selective translocator through the plasma membrane (Manceau et al. 2020).	Eukaryota	Metazoa, Chordata	TSPO2 of Homo sapiens
9.A.24.2.1	TspO homologue of 171 aas and 5 TMSs in a 1 + 4 TMS arrangement.	Bacteria	Pseudomonadota	TspO homologue of Maricaulis maris
9.A.24.2.2	CrtK protein of 166 aas and 5 TMSs.	Bacteria	Pseudomonadota	CrtK of Oceanicaulis sp.
9.A.24.3.1	Uncharacterized protein of 177 aas and 5 probable TMSs	Bacteria	Actinomycetota	UP of Mycobacterium vanbaalenii
9.A.24.3.2	Tryptophan-rich sensory proteinof 160 aas and 5 TMSs	Bacteria	Actinobacteria	TpsO of Nocardia soli
9.A.24.4.1	Uncharacterized protein, WcoO of 272 aas and 8 TMSs.	Bacteria	Actinomycetota	WcoO of Clavibacter michiganensis
9.A.24.4.2	Uncharacterized protein of 258 aas and 7 TMSs	Bacteria	Bacillota	UP of Bacillus selenitireducens
9.A.24.4.3	Uncharacterized protein of 290 aas and 8 TMSs	Bacteria	Actinomycetota	UP of Coriobacterium glomerans
9.A.24.4.4	Uncharacterized protein of 281 aas and 8 TMSs.	Eukaryota	Oomycota	UP of Phytophthora infestans (Potato late blight fungus)
9.A.24.4.5	Uncharacterized protein of 264 aas and 8 TMSs.	Eukaryota	Fungi, Mucoromycota	UP of Rhizophagus irregularis (Arbuscular mycorrhizal fungus) (Glomus intraradices)
9.A.24.4.6	Uncharacterized protein of 350 aas and 8 TMSs.	Eukaryota		UP of Guillardia theta
9.A.24.4.7	Uncharacterized protein of 277 aas and 7 TMSs	Bacteria	Actinomycetota	UP of Microbacterium yannicii
9.A.24.4.8	Uncharacterized protein of 236 aas and 8 TMSs in a 1 + 1 + 2 + 2 + 2 TMS arrangement.	Bacteria	Pseudomonadota	UP of Paracoccus zeaxanthinifaciens
9.A.24.4.9	Uncharacterized protein of 250 aas and 8 TMSs.	Bacteria	Pseudomonadota	UP of Henriciella aquimarina
9.A.24.4.10	Uncharacterized protein of 155 aas and 5 TMSs.	Archaea	Euryarchaeota	UP of Methanosarcina mazei