V-type proton ATPase subunit d 1 (ATP6V0D1)
The protein contains 351 amino acids for an estimated molecular weight of 40329 Da.
Subunit of the integral membrane V0 complex of the lysosomal proton-transporting V-type ATPase (v-ATPase) (PubMed:28296633, PubMed:30374053). V-ATPase is responsible for acidifying a variety of intracellular compartments in eukaryotic cells, thus providing most of the energy required for transport processes in the vacuolar system (PubMed:30374053). May play a role in coupling of proton transport and ATP hydrolysis (By similarity). 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 cilium biogenesis through regulation of the transport and the localization of proteins to the cilium (By similarity). (updated: Oct. 7, 2020)
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.
- 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.
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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Biological Process
ATP hydrolysis coupled proton transport
Biological process involved in interaction with host
Brain development
Cellular iron ion homeostasis
Cellular protein metabolic process
Cellular response to amino acid starvation
Cellular response to increased oxygen levels
Cilium assembly
Cilium assembly
Endoplasmic reticulum unfolded protein response
Insulin receptor signaling pathway
Ion transmembrane transport
IRE1-mediated unfolded protein response
Obsolete activation of signaling protein activity involved in unfolded protein response
Phagosome acidification
Phagosome maturation
Proton transmembrane transport
Proton transport
Regulation of macroautophagy
Transferrin transport
Transmembrane transport
Vacuolar acidification
Vacuolar transport
Cellular Component
Apical plasma membrane
Axon terminus
Early endosome
Endosome membrane
Extracellular exosome
Lysosomal membrane
Membrane
Obsolete cell
Phagocytic vesicle membrane
Plasma membrane proton-transporting V-type ATPase complex
Proton-transporting V-type ATPase, V0 domain
Synaptic vesicle
Vacuolar proton-transporting V-type ATPase complex
The reference OMIM entry for this protein is 607028
Atpase, h+ transporting, lysosomal, 38-kd, v0 subunit d, isoform 1; atp6v0d1
Vacuolar proton pump, v0 subunit d, isoform 1
V-atpase, subunit d
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 including C (603097), D, and E (108746).CLONING
Van Hille et al. (1993) cloned subunit D from an osteoclastoma tumor cDNA library with probes developed by PCR from the bovine cDNA sequence. The deduced 274-amino acid protein has a calculated molecular mass of about 32 kD and shows 99% sequence homology with bovine subunit D. Northern blot analysis revealed ubiquitous and comparable expression of a 1.8-kb transcript. While characterizing a genomic clone containing the HSD11B2 gene (614232), Agarwal and White (2000) identified the ATP6V0D1 gene. They obtained the complete ATP6V0D1 sequence from kidney cortical collecting duct cell cDNA and found that the deduced protein is identical to the mouse homolog with the exception of 2 conservative amino acid substitutions. PCR amplification revealed high expression of subunit D in kidney and placenta.GENE STRUCTURE
Agarwal and White (2000) determined that the ATP6V0D1 gene consists of 8 exons spanning approximately 19 kb. They found that the gene is located immediately adjacent to the HSD11B2 gene and is oriented in the opposite direction, with the 3-prime ends of the 2 genes only 0.5 kb apart. Stimulation of human kidney cortical collecting duct cells or choriocarcinoma cells indicated that their expression is regulated independently.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the ATP6V0D1 gene to chromosome 16 (TMAP stSG1825). Agarwal and White (2000) identified ATP6V0D1 on a genomic clone mapped to chromosome 16q22.GENE FUNCTION
Cruciat et al. (2010) found that the prorenin receptor (PRR; 300556) functions in a renin-independent manner as an adaptor between Wnt receptors and the V-ATPase complex. Moreover, PRR and V-ATPase were required to mediate Wnt signaling during anteroposterior patterning of Xenopus early central nervous system development. Cruciat et al. (2010) concluded that their results revealed an unsuspected role for the prorenin receptor, V-ATPase activity, and acidification during Wnt/beta-catenin (116806) signaling.MOLECULAR GENETICS
Agarwal and White (2000) screened the ATP6V0D1 gene in 17 hypertensive subjects and found no mutations. ... More on the omim web site
Oct. 20, 2020: 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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 607028 was added.