ATP synthase subunit alpha, mitochondrial (ATP5A1)
The protein contains 553 amino acids for an estimated molecular weight of 59751 Da.
Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Subunits alpha and beta form the catalytic core in F(1). Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits. Subunit alpha does not bear the catalytic high-affinity ATP-binding sites (By similarity). Binds the bacterial siderophore enterobactin and can promote mitochondrial accumulation of enterobactin-derived iron ions (PubMed:30146159). (updated: Nov. 7, 2018)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- 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.
- 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.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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| Variant | Description |
|---|---|
| dbSNP:rs2228437 | |
| dbSNP:rs2228436 | |
| COXPD22 | |
| MC5DN4 |
Biological Process
ATP biosynthetic process
ATP hydrolysis coupled proton transport
ATP synthesis coupled proton transport
Cellular metabolic process
Cristae formation
Embryo development
Lipid metabolic process
Mitochondrial ATP synthesis coupled proton transport
Negative regulation of endothelial cell proliferation
Positive regulation of blood vessel endothelial cell migration
Respiratory electron transport chain
Small molecule metabolic process
Cellular Component
Extracellular exosome
Extracellular matrix
Membrane
Mitochondrial inner membrane
Mitochondrial matrix
Mitochondrial proton-transporting ATP synthase complex
Mitochondrion
Myelin sheath
Plasma membrane
Proton-transporting ATP synthase complex
Proton-transporting ATP synthase complex, catalytic core F(1)
The reference OMIM entry for this protein is 164360
Atp synthase, h+ transporting, mitochondrial f1 complex, alpha subunit 1; atp5a1
Atp5a
Mitochondrial atp synthetase; atpm
Mitochondrial atp synthetase, oligomycin-resistant; omr
Modifier of min 2, mouse, homolog of; mom2
DESCRIPTION
The ATP5A1 gene encodes the alpha subunit of the mitochondrial ATP synthase F1 complex (Kataoka and Biswas, 1991).CLONING
ATP synthase is a multimeric complex consisting of at least 16 different polypeptides; 2 of these subunits are mitochondrially encoded and the remainder are produced by nuclear genes. Kataoka and Biswas (1991) reported the cloning of an ATP5A cDNA from a human LX-1 tumor cell library. They found that the gene encoded a 553-amino acid polypeptide that was 97% and 68% similar to the rat and yeast F1-ATP5A genes, respectively. Akiyama et al. (1994) isolated the human genomic clone of the ATP5A gene. Comparison of the promoter region of the ATP5A gene with the promoter region of the genes for the human ATP synthase beta subunit (ATP5B; 102910), and the human ATP synthase gamma subunit (ATP5C; 108729) indicated 3 common promoter sequences, suggesting that these 3 ATP synthase genes are coordinately regulated. Akiyama et al. (1994) presented evidence of cell type-specific regulation of ATP5A.GENE STRUCTURE
Akiyama et al. (1994) determined that the ATP5A gene contains 12 exons spanning 14 kb of the genome. Southern blot analysis revealed the presence of a single copy of the ATP5A gene and 2 pseudogenes in the human genome.MAPPING
Using a rat liver cDNA as a probe in the analysis of somatic cell hybrid DNAs, Jabs et al. (1994) found hybridization of ATP5A to both chromosomes 9 and 18. One of these may represent a pseudogene. Godbout et al. (1997) stated that ATP5A is the only functional gene among the 4 ATP5A-related genes in the human genome. By fluorescence in situ hybridization, they mapped this functional gene to chromosome 18q12-q21. Using somatic cell hybrids and fluorescence in situ hybridization, Godbout et al. (1997) mapped ATP5AP1, an ATP5A pseudogene, to chromosome 9p12. The other 2 pseudogenes are located on chromosomes 2 and 16. Baran et al. (2007) determined that the mouse Atp5a1 gene maps to distal chromosome 18.MOLECULAR GENETICS
- Mitochondrial Complex V Deficiency, Nuclear Type 4 In 2 sibs with fatal infantile mitochondrial encephalopathy and biochemical evidence of mitochondrial complex V deficiency (MC5DN4; 615228), Jonckheere et al. (2013) identified a heterozygous missense mutation in the ATP5A1 gene (R329C; 164360.0001) inherited from the unaffected father. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not present in 1,200 control exomes. The sibs expressed only the mutant allele, the father expressed both the mutant and wildtype allele, and the mother expressed only the wildtype allele. Although no mutations were identified in the mother's ATP5A1 gene, there was no evidence for a splicing defect, and MLPA excluded gene rearrangements; the mother had only about 60% ATP5A1 mRNA, consistent with a gene expression defect. SNP analysis indicated that both patients inherited the same maternal allele. Complementation of patient fibroblasts with wildtype ATP5A1 completely normalized complex V amount and activity. The findings indicated that the ATP5A1 defect found in these patients was disease-causing, even though the exact nature of the mutation inherited from the mother remained unknown. - Combined Oxidative Phosphorylation Deficiency 22 In 2 sisters, born of consanguineous Moroccan parents, with combined oxidative phosphorylation deficiency-22 (COXPD22; 616045) resulting in early death, Lieber ... More on the omim web site
Nov. 16, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 164360 was added.