ATP6V0A1 Membrane Protein Introduction

Introduction of ATP6V0A1

ATP6V0A1 is a 116-kD subunit of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. Acting as a vacuolar proton pump, the V-ATPase consists of a cytosolic V1 domain and a transmembrane V0 domain. The V0 domain consists of five different subunits: a, c, c’, c’’, and d. The V1 domain containing the ATP catalytic site is composed of three A, three B subunits, two G subunits and the C, D, E, F, and H subunits. ATP6V0A1 gene encodes one of three A subunit of V1 domain. At the same time, there are also three isoforms by alternative splicing of transcripts have been found for this gene. ATP6V0A1 is associated with clathrin-coated vesicles.

Function of ATP6V0A1 Membrane Protein

V-ATPase dependent organelle acidification is essential for such intracellular processes as zymogen activation, protein sorting, synaptic vesicle proton gradient generation, and receptor-mediated endocytosis. As a part of V-ATPase, ATP6V0A1 is indispensable for assembly and activity of the vacuolar ATPase and acts as a part of the hydrogen pump. It participates in many biological processes: ATP hydrolysis/synthesis coupled proton transport, insulin receptor signaling pathway, ion transmembrane transport, toxin transport, transferrin transport, neutrophil degranulation and so on. It is reported that ATP6V01 has a connection with clathrin-coated vesicles to play more roles. In addition, it has been reported that ATP6V0A1 may have a potential role in specific targeting and mediation of the enzyme for a particular organelle. A schematic representation of a proton pump is available in Fig 1.

Fig.1 Schematic Representation of proton pump mediating acidification of eukaryotic intracellular organelles.

Application of ATP6V0A1 Membrane Protein in Literature

1. Wei Z., et al. A common genetic variant in the 3'-UTR of vacuolar H+-ATPase ATP6V0A1 creates a micro-RNA motif to alter chromogranin A processing and hypertension risk. Circ Cardiovasc Genet. 2011, 4(4): 381-9. PubMed ID: 21558123
   
   

   This article suggests a succession of events whereby ATP6V0A1 3'-UTR variant T+3246C functioned: ATP6V0A1 expression, altering pH of vacuolar and therefore CHGA processing and exocytotic secretion are probably affected by different micro-RNA effects.

2. Antonacopoulou A.G., et al. POLR2F, ATP6V0A1 and PRNP expression in colorectal cancer: new molecules with prognostic significance. Anticancer Res. 2008, 28(2B): 1221-7. PubMed ID: 18505059
   
   

   This article suggests that POLR2F, PRNP, and ATP6V0A1 overexpression are associated with early disease relapse. On the other hand, the POLR2F and ATP6V0A1 levels are found to be related to survival and constituted prognostic factors in univariate analysis.

3. Tuttle A.M., et al. Rabconnectin-3a regulates vesicle endocytosis and canonical Wnt signaling in zebrafish neural crest migration. PLoS Biol. 2014, 12(5): e1001852. PubMed ID: 24802872
   
   

   This article suggests that Atp6v0a1 and Rbc3a can lead to endosomal maturation to regulate Wnt signaling and intracellular trafficking of Wnt receptors and cadherins required for NC migration and cell fate determination.

4. Morimura T., et.al. The proton pump inhibitor inhibits cell growth and induces apoptosis in human hepatoblastoma. Pediatr Surg Int. 2008, 24(10): 1087-94. PubMed ID: 18712525
   
   

   This report shows that three of the 27 V-ATPase-related transcripts (ATP6V0A1, ATP6V0D2, and ATP6V1B1) are more lowly expressed in the Baf-A1-treated cells than in the Baf-A1-free cells by the analysis of hepatoblastoma cells using the Gene Chip expression analysis arrays.

5. Pietrement C., et.al. Distinct expression patterns of different subunit isoforms of the V-ATPase in the rat epididymis. Biol Reprod. 2006, 74(1): 185-94. PubMed ID: 16192400
   
   

   This article reports the localization of V-ATPase subunit isoforms ATP6V0A1, previously labeled a1, in epithelial cells of the rat vas deferens and epididymis.

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