ATP6V0A4 explained

V-type proton ATPase 116 kDa subunit a isoform 4 is an enzyme that in humans is encoded by the ATP6V0A4 gene.^{[1] [2] [3]}

Function

This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of intracellular compartments of eukaryotic cells. V-ATPase dependent acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A and three B subunits, two G subunits plus the C, D, E, F, and H subunits. The V1 domain contains the ATP catalytic site. The V0 domain consists of five different subunits: a, c, c', c'', and d. This gene is one of four genes in man and mouse that encode different isoforms of the a subunit. Alternatively spliced transcript variants encoding the same protein have been described. Mutations in this gene are associated with renal tubular acidosis associated with preserved hearing.^[3]

Interactions

ATP6V0A4 has been shown to interact with PFKM.^[4]

Further reading

• Finbow ME, Harrison MA . The vacuolar H+-ATPase: a universal proton pump of eukaryotes . Biochem. J. . 324 . 3 . 697–712 . 1997 . 9210392 . 1218484 . 10.1042/bj3240697.
• Stevens TH, Forgac M . Structure, function and regulation of the vacuolar (H+)-ATPase . Annu. Rev. Cell Dev. Biol. . 13 . 779–808 . 1997 . 9442887 . 10.1146/annurev.cellbio.13.1.779 .
• Nelson N, Harvey WR . Vacuolar and plasma membrane proton-adenosinetriphosphatases . Physiol. Rev. . 79 . 2 . 361–85 . 1999 . 10221984 . 10.1152/physrev.1999.79.2.361. 1477911 .
• Forgac M . Structure and properties of the vacuolar (H+)-ATPases . J. Biol. Chem. . 274 . 19 . 12951–4 . 1999 . 10224039 . 10.1074/jbc.274.19.12951 . free .
• Kane PM . Introduction: V-ATPases 1992-1998 . J. Bioenerg. Biomembr. . 31 . 1 . 3–5 . 1999 . 10340843 . 10.1023/A:1001884227654 .
• Wieczorek H, Brown D, Grinstein S, Ehrenfeld J, Harvey WR . Animal plasma membrane energization by proton-motive V-ATPases . BioEssays . 21 . 8 . 637–48 . 1999 . 10440860 . 10.1002/(SICI)1521-1878(199908)21:8<637::AID-BIES3>3.0.CO;2-W . 23505139 .
• Brown D, Breton S . H(+)V-ATPase-dependent luminal acidification in the kidney collecting duct and the epididymis/vas deferens: vesicle recycling and transcytotic pathways . J. Exp. Biol. . 203 . Pt 1 . 137–45 . 2000 . 10.1242/jeb.203.1.137 . 10600682 .
• Nishi T, Forgac M . The vacuolar (H+)-ATPases--nature's most versatile proton pumps . Nat. Rev. Mol. Cell Biol. . 3 . 2 . 94–103 . 2002 . 11836511 . 10.1038/nrm729 . 21122465 .
• Kawasaki-Nishi S, Nishi T, Forgac M . Proton translocation driven by ATP hydrolysis in V-ATPases . FEBS Lett. . 545 . 1 . 76–85 . 2003 . 12788495 . 10.1016/S0014-5793(03)00396-X . 10507213 .
• Morel N . Neurotransmitter release: the dark side of the vacuolar-H+ATPase . Biol. Cell . 95 . 7 . 453–7 . 2003 . 14597263 . 10.1016/S0248-4900(03)00075-3 . 17519696 . free .

Notes and References

1. Karet FE, Finberg KE, Nayir A, Bakkaloglu A, Ozen S, Hulton SA, Sanjad SA, Al-Sabban EA, Medina JF, Lifton RP . Localization of a gene for autosomal recessive distal renal tubular acidosis with normal hearing (rdRTA2) to 7q33-34 . Am. J. Hum. Genet. . 65 . 6 . 1656–65 . Jan 2000 . 10577919 . 1288376 . 10.1086/302679 .
2. Smith AN, Skaug J, Choate KA, Nayir A, Bakkaloglu A, Ozen S, Hulton SA, Sanjad SA, Al-Sabban EA, Lifton RP, Scherer SW, Karet FE . Mutations in ATP6N1B, encoding a new kidney vacuolar proton pump 116-kD subunit, cause recessive distal renal tubular acidosis with preserved hearing . Nat. Genet. . 26 . 1 . 71–5 . Oct 2000 . 10973252 . 10.1038/79208 . 19880326 .
3. Web site: Entrez Gene: ATP6V0A4 ATPase, H+ transporting, lysosomal V0 subunit a4.
4. Su Y, Zhou A, Al-Lamki RS, Karet FE . The a-subunit of the V-type H+-ATPase interacts with phosphofructokinase-1 in humans . J. Biol. Chem. . 278 . 22 . 20013–8 . May 2003 . 12649290 . 10.1074/jbc.M210077200 . free .