ADP/ATP translocase 3 (SLC25A6)
The protein contains 298 amino acids for an estimated molecular weight of 32866 Da.
ADP:ATP antiporter that mediates import of ADP into the mitochondrial matrix for ATP synthesis, and export of ATP out to fuel the cell (By similarity). Cycles between the cytoplasmic-open state (c-state) and the matrix-open state (m-state): operates by the alternating access mechanism with a single substrate-binding site intermittently exposed to either the cytosolic (c-state) or matrix (m-state) side of the inner mitochondrial membrane (By similarity). In addition to its ADP:ATP antiporter activity, also involved in mitochondrial uncoupling and mitochondrial permeability transition pore (mPTP) activity (PubMed:15033708). Plays a role in mitochondrial uncoupling by acting as a proton transporter: proton transport uncouples the proton flows via the electron transport chain and ATP synthase to reduce the efficiency of ATP production and cause mitochondrial thermogenesis (By similarity). Proton transporter activity is inhibited by ADP:ATP antiporter activity, suggesting that SLC25A6/ANT3 acts as a master regulator of mitochondrial energy output by maintaining a delicate balance between ATP production (ADP:ATP antiporter activity) and thermogenesis (proton transporter activity) (By similarity). Proton transporter activity requires free fatty acids as cofactor, but does not transport it (By similarity). Also plays a key role in mPTP opening, a non-specific pore that enables free passage of the mitochondrial membranes to solutes of up to 1.5 kDa, and which contributes to cell deat (updated: April 7, 2021)
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.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
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.
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| Variant | Description |
|---|---|
| empty |
Biological Process
Apoptotic process
Mitochondrial ADP transmembrane transport
Mitochondrial ATP transmembrane transport
Protein targeting to mitochondrion
Regulation of insulin secretion
Viral process
The reference OMIM entry for this protein is 300151
Solute carrier family 25 (mitochondrial carrier, adenine nucleotide translocator), member a6; slc25a6
Adenine nucleotide translocator 3; ant3
Adp/atp translocator of liver
Adp/atp translocase 3
Adp/atp carrier 3; aac3
CLONING
Schiebel et al. (1993) cloned a highly conserved pseudoautosomal gene by selecting a cDNA clone with a microdissected clone from chromosomal subregion Xp22.3. They found that it encodes ANT3, a member of the ADP/ATP translocase family that plays a fundamental role in cellular energy metabolism. The ANT3 gene had previously been characterized by Houldsworth and Attardi (1988) and by Cozens et al. (1989).MAPPING
The gene encoding adenine nucleotide translocator-3 is located in the pseudoautosomal region (PAR) at the end of the short arm of the X and Y chromosomes. See also 403000. Schiebel et al. (1993) determined that the ANT3 gene is located approximately 1,300 kb from the telomere of the X chromosome, proximal to the pseudoautosomal gene CSF2RA (306250), and escapes X inactivation. A homolog of ANT3, ANT2 (300150), maps to Xq13-q26 and is subject to X inactivation. The physical location of the ANT3 gene was determined by pulsed field mapping. From the location of a CpG island, they determined the orientation of the gene to be from centromere toward the telomere. It is probably directly adjacent to CSF2RA. All pseudogenes of the ANT gene family seem to lack introns. Schiebel et al. (1993) identified an intronless ANT3 pseudogene on chromosome 9. Slim et al. (1993) identified the ANT3 gene in a clone microdissected from Xp22.3. It contained in its first intron a CpG island mapped 13,000 kb from the telomere. They showed that the gene is transcribed from the Y chromosome and from both the active and inactive X chromosomes.EVOLUTION
Comparative in situ hybridization in various primate species revealed a pseudoautosomal location for the ANT3 gene and an X-specific location for the steroid sulfatase gene (STS; 300747) throughout the higher primate species up to the New World monkeys. However, Toder et al. (1995) found that ANT3 and STS map together on an autosome of 2 prosimian species of the genera Lemur and Eulemur. These results suggested an autosomal-to-X/Y translocation after the simians radiated from the prosimians, resulting in a pseudoautosomal location of genes such as ANT3 and STS. In simian primates, STS then became X-specific by a pericentric inversion in the Y chromosome followed by mutational inactivation of the Y allele. ... More on the omim web site
April 10, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
June 29, 2020: Protein entry updated
Automatic update: OMIM entry 300151 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).