V-type proton ATPase catalytic subunit A (ATP6V1A)
The protein contains 617 amino acids for an estimated molecular weight of 68304 Da.
Catalytic subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (By similarity). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (PubMed:32001091). In aerobic conditions, involved in intracellular iron homeostasis, thus triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation (PubMed:28296633). May play a role in neurite development and synaptic connectivity (PubMed:29668857).', '(Microbial infection) Plays an important role in virion uncoating during Rabies virus replication after membrane fusion. Specifically, participates in the dissociation of incoming viral matrix M proteins uncoating through direct interaction. (updated: June 2, 2021)
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.
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Biological Process
ATP hydrolysis coupled proton transport
ATP metabolic process
Biological process involved in interaction with host
Cellular iron ion homeostasis
Cellular response to amino acid starvation
Cellular response to increased oxygen levels
Insulin receptor signaling pathway
Ion transmembrane transport
Phagosome acidification
Phagosome maturation
Proton transmembrane transport
Regulation of macroautophagy
Transferrin transport
Transmembrane transport
Transport
Cellular Component
Apical plasma membrane
Cytosol
Extracellular exosome
Integral component of plasma membrane
Intracellular membrane-bounded organelle
Lysosomal membrane
Microvillus
Mitochondrion
Myelin sheath
Nucleoplasm
Obsolete cell
Plasma membrane
Proton-transporting two-sector ATPase complex
Proton-transporting V-type ATPase, V1 domain
Vacuolar membrane
The reference OMIM entry for this protein is 607027
Atpase, h+ transporting, lysosomal alpha polypeptide, 70-kd, isoform 1; atp6v1a1
V-atpase a subunit 1
Vacuolar proton pump, alpha subunit 1
Va68 ho68, included
DESCRIPTION
The vacuolar-type H(+)-ATPase (V-ATPase) is responsible for the acidification of endosomes, lysosomes, and other intracellular organelles. It is also involved in hydrogen ion transport across the plasma membrane into the extracellular space. The V-ATPase is a multisubunit complex with cytosolic and transmembrane domains. The cytosolic catalytic domain consists of 3 A subunits and 3 B subunits, which bind and hydrolyze ATP, as well as regulatory accessory subunits.CLONING
Van Hille et al. (1993) cloned a partial cDNA clone for an A subunit isoform, which they designated VA68, from a human osteoclastoma tumor cDNA library by PCR using degenerate primers based on the bovine sequence. They obtained a full-length clone from a genomic library. The deduced 617-amino acid protein has a predicted molecular mass of about 68 kD and shows 99% sequence identity with the bovine brain subunit A. Northern blot analysis revealed ubiquitous expression of a major 4.8-kb band and a minor 3.4-kb band. They also identified a variant, which they designated HO68, encoding a 615-amino acid protein. By RNase protection assays and in situ hybridization, van Hille et al. (1995) determined that expression of the HO68 variant was specific to the osteoclastoma originally used to construct the cDNA library.GENE FUNCTION
Amino acids activate the Rag GTPases, which promote the translocation of mTORC1 (see 601231) to the lysosomal surface, the site of mTORC1 activation. Zoncu et al. (2011) found that the v-ATPase is necessary for amino acids to activate mTORC1. The v-ATPase engages in extensive amino-acid sensitive interactions with the Ragulator, a scaffolding complex that anchors the Rag GTPases to the lysosome. In a cell-free system, ATP hydrolysis by the v-ATPase was necessary for amino acids to regulate the v-ATPase-Ragulator interaction and promote mTORC1 translocation. The results obtained in vitro and in human cells suggested that amino acid signaling begins within the lysosomal lumen. Zoncu et al. (2011) concluded that their results identified the v-ATPase as a component of the mTOR pathway and delineated a lysosome-associated machinery for amino acid sensing.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the ATP6V1A1 gene to chromosome 3 (TMAP stSG364). ... More on the omim web site
July 1, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Nov. 16, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 607027 was added.