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21  structures 3601  species 0  interactions 4992  sequences 34  architectures

Family: TspO_MBR (PF03073)

Summary: TspO/MBR family

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Translocator protein". More...

Translocator protein Edit Wikipedia article

translocator protein (18kDa)
Identifiers
SymbolTSPO
Alt. symbolsBZRP
NCBI gene706
HGNC1158
OMIM109610
RefSeqNM_007311
UniProtP30536
Other data
LocusChr. 22 q13.3

TSPO is a protein associated with GABA receptors.

External links

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This is the Wikipedia entry entitled "Tryptophan-rich sensory protein". More...

Tryptophan-rich sensory protein Edit Wikipedia article

TspO_MBR
Identifiers
SymbolTspO_MBR
PfamPF03073
InterProIPR004307

Tryptophan-rich sensory proteins are a family of proteins that are transmembrane signalling. In both prokaryotes and mitochondria they are localized to the outer membrane, and have been shown to bind and transport dicarboxylic tetrapyrrole intermediates of the haem biosynthetic pathway.[1][2] They are associated with the major outer membrane porins (in prokaryotes) and with the voltage-dependent anion channel (in mitochondria).[3]

TspO of Rhodobacter sphaeroides is involved in signal transduction, functioning as a negative regulator of the expression of some photosynthesis genes (PpsR/AppA repressor/antirepressor regulon). This down-regulation is believed to be in response to oxygen levels. TspO works through (or modulates) the PpsR/AppA system and acts upstream of the site of action of these regulatory proteins.[4] It has been suggested that the TspO regulatory pathway works by regulating the efflux of certain tetrapyrrole intermediates of the haem/bacteriochlorophyll biosynthetic pathways in response to the availability of molecular oxygen, thereby causing the accumulation of a biosynthetic intermediate that serves as a corepressor for the regulated genes.[5] A homologue of the TspO protein in Rhizobium meliloti (Sinorhizobium meliloti) is involved in regulating expression of the ndi locus in response to stress conditions.[6] There is evidence that the S. meliloti TspO acts through, or in addition to, the FixL regulatory system.

In animals, the peripheral-type benzodiazepine receptor (PBR, MBR) is a mitochondrial protein (located in the outer mitochondrial membrane) characterised by its ability to bind with nanomolar affinity to a variety of benzodiazepine-like drugs, as well as to dicarboxylic tetrapyrrole intermediates of the haem biosynthetic pathway. Depending upon the tissue, it was shown to be involved in steroidogenesis, haem biosynthesis, apoptosis, cell growth and differentiation, mitochondrial respiratory control, and immune and stress response, but the precise function of the PBR remains unclear. The role of PBR in the regulation of cholesterol transport from the outer to the inner mitochondrial membrane, the rate-determining step in steroid biosynthesis, has been studied in detail. PBR is required for the binding, uptake and release, upon ligand activation, of the substrate cholesterol.[7] PBR forms a multimeric complex with the voltage-dependent anion channel (VDAC) [3] and adenine nucleotide carrier.[1] Molecular modeling of PBR suggested that it might function as a channel for cholesterol. Indeed, cholesterol uptake and transport by bacterial cells was induced upon PBR expression. Mutagenesis studies identified a cholesterol recognition/interaction motif (CRAC) in the cytoplasmic C terminus of PBR.[8][9]

In complementation experiments, rat PBR (pk18) functionally substitutes for its homologue TspO in R. sphaeroides, negatively affecting transcription of specific photosynthesis genes.[10] This suggests that PBR may function as an oxygen sensor, transducing an oxygen-triggered signal leading to an adaptive cellular response.

These observations suggest that fundamental aspects of this receptor and the downstream signal transduction pathway are conserved in bacteria and higher eukaryotic mitochondria. The alpha-3 subdivision of the purple bacteria is considered to be a likely source of the endosymbiont that ultimately gave rise to the mitochondrion. Therefore, it is possible that the mammalian PBR remains both evolutionarily and functionally related to the TspO of R. sphaeroides.

References

  1. ^ a b McEnery MW, Snowman AM, Trifiletti RR, Snyder SH (1992). "Isolation of the mitochondrial benzodiazepine receptor: association with the voltage-dependent anion channel and the adenine nucleotide carrier". Proc. Natl. Acad. Sci. U.S.A. 89 (8): 3170–4. PMC 48827. PMID 1373486. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  2. ^ Yeliseev AA, Kaplan S (1995). "A sensory transducer homologous to the mammalian peripheral-type benzodiazepine receptor regulates photosynthetic membrane complex formation in Rhodobacter sphaeroides 2.4.1". J. Biol. Chem. 270 (36): 21167–75. PMID 7673149. {{cite journal}}: Unknown parameter |month= ignored (help)
  3. ^ a b Garnier M, Dimchev AB, Boujrad N, Price JM, Musto NA, Papadopoulos V (1994). "In vitro reconstitution of a functional peripheral-type benzodiazepine receptor from mouse Leydig tumor cells". Mol. Pharmacol. 45 (2): 201–11. PMID 8114671. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  4. ^ Zeng X, Kaplan S (2001). "TspO as a modulator of the repressor/antirepressor (PpsR/AppA) regulatory system in Rhodobacter sphaeroides 2.4.1". J. Bacteriol. 183 (21): 6355–64. doi:10.1128/JB.183.21.6355-6364.2001. PMC 100131. PMID 11591680. {{cite journal}}: Unknown parameter |month= ignored (help)
  5. ^ Yeliseev AA, Kaplan S (1999). "A novel mechanism for the regulation of photosynthesis gene expression by the TspO outer membrane protein of Rhodobacter sphaeroides 2.4.1". J. Biol. Chem. 274 (30): 21234–43. PMID 10409680. {{cite journal}}: Unknown parameter |month= ignored (help)
  6. ^ Davey ME, de Bruijn FJ (2000). "A homologue of the tryptophan-rich sensory protein TspO and FixL regulate a novel nutrient deprivation-induced Sinorhizobium meliloti locus". Appl. Environ. Microbiol. 66 (12): 5353–9. PMC 92468. PMID 11097914. {{cite journal}}: Unknown parameter |month= ignored (help)
  7. ^ Papadopoulos V, Amri H, Li H, Yao Z, Brown RC, Vidic B, Culty M (2001). "Structure, function and regulation of the mitochondrial peripheral-type benzodiazepine receptor". Therapie. 56 (5): 549–56. PMID 11806292.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ Li H, Yao Z, Degenhardt B, Teper G, Papadopoulos V (2001). "Cholesterol binding at the cholesterol recognition/ interaction amino acid consensus (CRAC) of the peripheral-type benzodiazepine receptor and inhibition of steroidogenesis by an HIV TAT-CRAC peptide". Proc. Natl. Acad. Sci. U.S.A. 98 (3): 1267–72. doi:10.1073/pnas.031461598. PMC 14743. PMID 11158628. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  9. ^ Papadopoulos V (2003). "Peripheral benzodiazepine receptor: structure and function in health and disease". Ann Pharm Fr. 61 (1): 30–50. PMID 12589253. {{cite journal}}: Unknown parameter |month= ignored (help)
  10. ^ Yeliseev AA, Krueger KE, Kaplan S (1997). "A mammalian mitochondrial drug receptor functions as a bacterial "oxygen" sensor". Proc. Natl. Acad. Sci. U.S.A. 94 (10): 5101–6. PMC 24638. PMID 9144197. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
This article incorporates text from the public domain Pfam and InterPro: IPR004307

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

TspO/MBR family Provide feedback

Tryptophan-rich sensory protein (TspO) is an integral membrane protein that acts as a negative regulator of the expression of specific photosynthesis genes in response to oxygen/light [1]. It is involved in the efflux of porphyrin intermediates from the cell. This reduces the activity of coproporphyrinogen III oxidase, which is thought to lead to the accumulation of a putative repressor molecule that inhibits the expression of specific photosynthesis genes. Several conserved aromatic residues are necessary for TspO function: they are thought to be involved in binding porphyrin intermediates [3]. In [2] the rat mitochondrial peripheral benzodiazepine receptor (MBR) was shown to not only retain its structure within a bacterial outer membrane, but also to be able to functionally substitute for TspO in TspO- mutants, and to act in a similar manner to TspO in its in situ location: the outer mitochondrial membrane. The biological significance of MBR remains unclear, however. It is thought to be involved in a variety of cellular functions, including cholesterol transport in steroidogenic tissues.

Literature references

  1. Yeliseev AA, Kaplan S; , J Biol Chem 1995;270:21167-21175.: A sensory transducer homologous to the mammalian peripheral-type benzodiazepine receptor regulates photosynthetic membrane complex formation in Rhodobacter sphaeroides 2.4.1. PUBMED:7673149 EPMC:7673149

  2. Yeliseev AA, Krueger KE, Kaplan S; , Proc Natl Acad Sci U S A 1997;94:5101-5106.: A mammalian mitochondrial drug receptor functions as a bacterial oxygen sensor. PUBMED:9144197 EPMC:9144197

  3. Yeliseev AA, Kaplan S; , J Biol Chem 2000;275:5657-5667.: TspO of rhodobacter sphaeroides. A structural and functional model for the mammalian peripheral benzodiazepine receptor. PUBMED:10681549 EPMC:10681549


This tab holds annotation information from the InterPro database.

InterPro entry IPR004307

Members of this group are involved in transmembrane signalling. In both prokaryotes and mitochondria they are localized to the outer membrane, and have been shown to bind and transport dicarboxylic tetrapyrrole intermediates of the haem biosynthetic pathway [ PUBMED:1373486 , PUBMED:7673149 ]. They are associated with the major outer membrane porins (in prokaryotes) and with the voltage-dependent anion channel (in mitochondria) [ PUBMED:8114671 ].

Rhodobacter sphaeroides TspO (previously CrtK) is involved in signal transduction, functioning as a negative regulator of the expression of some photosynthesis genes (PpsR/AppA repressor/antirepressor regulon). This down-regulation is believed to be in response to oxygen levels. TspO works through (or modulates) the PpsR/AppA system and acts upstream of the site of action of these regulatory proteins [ PUBMED:11591680 ]. It has been suggested that the TspO regulatory pathway works by regulating the efflux of certain tetrapyrrole intermediates of the haem/bacteriochlorophyll biosynthetic pathways in response to the availability of molecular oxygen, thereby causing the accumulation of a biosynthetic intermediate that serves as a corepressor for the regulated genes [ PUBMED:10409680 ]. A homologue of the TspO protein in Rhizobium meliloti (Sinorhizobium meliloti) is involved in regulating expression of the ndi locus in response to stress conditions [ PUBMED:11097914 ]. There is evidence that the S. meliloti TspO acts through, or in addition to, the FixL regulatory system.

In animals, translocator protein (TSPO), previously known as peripheral-type benzodiazepine receptor (PBR, MBR) is a mitochondrial protein (located in the outer mitochondrial membrane) where it forms a complex with several proteins of the mitochondrial permeability transition pore (MPTP). TSPO is involved in multiple processes, including regulation of cell death, cholesterol transport and steroid biosynthesis, mitochondrial respiration and oxidation and mitochondrial protein import [ PUBMED:23518318 , PUBMED:22364127 ].

These observations suggest that fundamental aspects of this receptor and the downstream signal transduction pathway are conserved in bacteria and higher eukaryotic mitochondria. The alpha-3 subdivision of the purple bacteria is considered to be a likely source of the endosymbiont that ultimately gave rise to the mitochondrion. Therefore, it is possible that the mammalian PBR remains both evolutionarily and functionally related to the TspO of R. sphaeroides.

Gene Ontology

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Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Alignments

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  Seed
(425)
Full
(4992)
Representative proteomes UniProt
(17506)
RP15
(780)
RP35
(2393)
RP55
(4857)
RP75
(7920)
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PP/heatmap 1 View           

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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  Seed
(425)
Full
(4992)
Representative proteomes UniProt
(17506)
RP15
(780)
RP35
(2393)
RP55
(4857)
RP75
(7920)
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  Seed
(425)
Full
(4992)
Representative proteomes UniProt
(17506)
RP15
(780)
RP35
(2393)
RP55
(4857)
RP75
(7920)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_1882 (release 6.4)
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Mifsud W
Number in seed: 425
Number in full: 4992
Average length of the domain: 144.3 aa
Average identity of full alignment: 26 %
Average coverage of the sequence by the domain: 79.08 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 24.0 24.0
Trusted cut-off 24.0 24.0
Noise cut-off 23.9 23.9
Model length: 143
Family (HMM) version: 18
Download: download the raw HMM for this family

Species distribution

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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the TspO_MBR domain has been found. There are 21 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A044S426 View 3D Structure Click here
A0A044S432 View 3D Structure Click here
A0A044S438 View 3D Structure Click here
A0A077YUV1 View 3D Structure Click here
A0A077ZJS4 View 3D Structure Click here
A0A0D2GA96 View 3D Structure Click here
A0A0K0DYX3 View 3D Structure Click here
A0A175W3T1 View 3D Structure Click here
A0A1C1CLR2 View 3D Structure Click here
A0A1D6LIV7 View 3D Structure Click here
A0A2K6VQR1 View 3D Structure Click here
A0A3P7ED78 View 3D Structure Click here
A0A3P7FNG7 View 3D Structure Click here
A0A3P7PV47 View 3D Structure Click here
A0A5S6PFU0 View 3D Structure Click here
B6SQ48 View 3D Structure Click here
B7F8G3 View 3D Structure Click here
C7FZU5 View 3D Structure Click here
E2RDM9 View 3D Structure Click here
G4VJX2 View 3D Structure Click here
I1JQL0 View 3D Structure Click here
I1L102 View 3D Structure Click here
I1MGL3 View 3D Structure Click here
I1NB49 View 3D Structure Click here
K0EZW7 View 3D Structure Click here
M0RA45 View 3D Structure Click here
O28797 View 3D Structure Click here
O34694 View 3D Structure Click here
O82245 View 3D Structure Click here
O94327 View 3D Structure Click here
P16257 View 3D Structure Click here
P17057 View 3D Structure Click here
P30535 View 3D Structure Click here
P30536 View 3D Structure Click here
P50637 View 3D Structure Click here
Q5TGU0 View 3D Structure Click here
Q5XJB6 View 3D Structure Click here
Q6UN27 View 3D Structure Click here
Q81BL7 View 3D Structure Click here
Q8KBX2 View 3D Structure Click here