V-ATPases, or Vacuolar ATPases, are present in plasma membranes in a wide variety of cell types and organellar membranes where they carry out several important functions. Their most important roles include those played in maintaining pH homeostasis, synaptic transmission, coupled transport across membranes, acidifying the acrosome of the sperm, and tumor metastasis. The protein in itself, is a heteromultimeric one and is made up of several subunits. Structurally, the protein has two regions, one external to the membrane, which carries out the hydrolysis of ATP and one integral to the membrane, which carries out the proton translocation. The region integral to the membrane, also known as V0, is itself composed of at least five different subunits. The ATP6V0A2 gene codes for the a2 subunit of this protein.
The exact functions of the a2 subunit are less clear. But it is understood that this subunit is directly involved in protein transport and has also been shown to be involved in recruiting proteins which regulate vesicular trafficking. Recent research also shows that this subunit has an important role to play in the active functioning of the Golgi apparatus, specifically the glycosylation function, by controlling the Golgi pH.
The ATP6V0A2 gene is located on chromosome 12q24.3. The entire gene spans a length of about 47.5 Kb. The protein coded for by this gene consists of 856 amino acids, and weighs about 98 kDa. Once embedded in the membrane, the protein acts as an anchor for the large ATPase protein complex. There are four different isoforms of this subunit.
Kornak et al. (2008) undertook a molecular study of several families with patients affected by Autosomal Recessive Cutis Laxa Type II (ARCL2) or Wrinkly Skin Syndrome (WSS). This included four Omani families with 11 members affected by WSS. Homozygosity mapping in these families identified a homozygous region on chromomsome 12q24, which was further refined to 5.7 Mb locus using polymorphic markers. The locus was scanned for genes related to proteins found in the Golgi apparatus, and the ATP6V0A2 gene was identified. Mutations in this gene were found in all four of the Omani families. In three of these families, the mutation caused a frame shift in the protein (V66fsX107), leading to a premature stop in the cytoplasmic N-terminus. In the fourth family, however, the mutation caused a frame shift (T643fsX683) that resulted in a truncation in the transmembrane segment VI. By analyzing patient fibroblasts, Kornak et al. (2008) were unable to find any major alterations in the Golgi morphology. However, there was a delay in the retrograde translocation of golgi membranes to the ER. Kornak et al. (2008) were of the opinion that defects in the ATP6V0A2 protein resulted in an impairment of vesicle fusion with the ER and possibly, also a defect in pH regulation. These defects would lead to impairment in the protein glycosylation machinery, resulting in the congenital glycosylation defects seen in WSS and ARCL2.