ADP/ATP translocase 2 (SLC25A5)
The protein contains 298 amino acids for an estimated molecular weight of 32852 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 (By similarity). 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 SLC25A5/ANT2 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). Probably mediates mitochondrial uncoupling in tissues that do not express UCP1 (By similarity). Also plays a key role in mPTP opening, a non-specific pore that enables free passage (updated: April 7, 2021)
Protein identification was indicated in the following studies:
- 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.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- 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.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| dbSNP:rs371749 |
Biological Process
Adaptive thermogenesis
Adenine nucleotide transport
B cell differentiation
Cellular response to leukemia inhibitory factor
Chromosome segregation
Erythrocyte differentiation
Mitochondrial ADP transmembrane transport
Mitochondrial ATP transmembrane transport
Negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway
Positive regulation of cell population proliferation
Positive regulation of mitophagy
Regulation of insulin secretion
Regulation of mitochondrial membrane permeability
Viral process
Cellular Component
Integral component of plasma membrane
Membrane
Membrane raft
Mitochondrial inner membrane
Mitochondrial nucleoid
Mitochondrial permeability transition pore complex
Mitochondrion
MMXD complex
Myelin sheath
Nucleus
Molecular Function
Adenine nucleotide transmembrane transporter activity
Adenine transmembrane transporter activity
ATP transmembrane transporter activity
ATP:ADP antiporter activity
Oxidative phosphorylation uncoupler activity
Proton transmembrane transporter activity
RNA binding
Ubiquitin protein ligase binding
The reference OMIM entry for this protein is 300150
Solute carrier family 25 (mitochondrial carrier, adenine nucleotide translocator), member a5; slc25a5
Adenine nucleotide translocator 2; ant2
Adp/atp translocator of fibroblasts
Adp/atp translocase 2
Adp/atp carrier 2; aac2
DESCRIPTION
ADP/ATP translocase, the most abundant mitochondrial protein, is an integral component of the inner mitochondrial membrane. It facilitates exchange of ADP and ATP between the cytosol and the mitochondria, thereby linking the subcellular compartment of ATP production to those of ATP utilization. SLC25A5 is 1 of at least 3 transcriptionally active ADP/ATP translocase genes in humans (Chen et al., 1990). Battini et al. (1987) cloned an ADP/ATP translocase gene from an Okayama-Berg library derived from SV40-transformed human fibroblasts. Ku et al. (1990) cloned and sequenced the ANT2 gene. Chen et al. (1990) isolated 7 ADP/ATP translocase pseudogenes from recombinant human genomic libraries. Each pseudogene sequence had more than 85% identity with the sequence of the translocase cDNA derived from fibroblast mRNA, but each had mutations that precluded synthesis of a functional protein.GENE FUNCTION
Mitochondrial nucleoids are large complexes containing, on average, 5 to 7 mitochondrial DNA (mtDNA) genomes and several proteins involved in mtDNA replication and transcription, as well as related processes. Bogenhagen et al. (2008) had previously shown that ANT2 was associated with native purified HeLa cell nucleoids. Using a formaldehyde crosslinking technique, they found that ANT2 copurified with mtDNA and was a core nucleoid protein. Ito et al. (2010) showed that ANT2 coprecipitated with XPD (ERCC2; 126340), MIP18 (FAM96B; 614778), MMS19 (614777), and CIAO1 (604333) in a protein complex that was required for chromosome segregation in human cell lines.GENE STRUCTURE
Ku et al. (1990) determined that, like the other 2 ANT genes (103220, 300151), ANT2 has 4 exons. They identified differences in the sequence motif in the 5-prime-flanking regions of the 3 human translocase genes that could account for differences in the cell-type-specific and proliferation-associated expression. Using an intron probe derived from a partial clone of the ANT2 gene, Chen et al. (1990) localized the gene to chromosome Xq13-q26. The assignment to the X chromosome and a particular region thereof was performed by analysis of somatic cell hybrids. By study of somatic cell hybrids containing different portions of the human X chromosome, Schiebel et al. (1994) narrowed the assignment to chromosome Xq24-q25. In connection with the previous assignment to Xq13-q26, the consensus location can be said to be Xq24-q26.ANIMAL MODEL
The mitochondrial permeability transition pore (mtPTP), a protein complex that includes the ANTs, mediates the sudden increase in inner mitochondrial membrane permeability that is a common feature of apoptosis. Kokoszka et al. (2004) confirmed that the mouse genome contains only 2 Ant genes, Ant1 and Ant2. They inactivated both Ant genes in mouse liver and analyzed mtPTP activation in isolated mitochondria and the induction of cell death in hepatocytes. Mitochondria lacking Ant could still undergo inner membrane permeability transition and release cytochrome c (123970). However, more Ca(2+) than usual was required to activate mtPTP, and the pore could not be regulated by Ant ligands, including adenine nucleotides. Hepatocytes without Ant remained competent to respond to various initiators of cell death. In addition, mutant mouse liver mitochondria showed respiration rates that were almost twice that of controls and that were unresponsive to the addition of ADP. The mitochondrial membrane potential ... More on the omim web site
April 10, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Nov. 16, 2018: Protein entry updated
Automatic update: OMIM entry 300150 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).