F
IPR006544

P-type ATPase, subfamily V

InterPro entry
Short nameP-type_TPase_V
Overlapping
homologous
superfamilies
 
family relationships

Description

This entry includes P-type ATPases from eukaryotes that form a different clade, designated subfamily V (P5-ATPases)
[1]
. P-type ATPases use ATP for intracellular cation homeostasis and are required for proper lysosomal and mitochondria maintenance
[13, 11]
, also playing a role in the maintenance of neuronal integrity
[12]
. P5-type ATPases can be subdivided in two subtypes based on the conservation of residues in the transmembrane domain, the P5A-type, which localize to the ER membrane (ATP13A1 from human and SPF1 from yeast), and P5B-type ATPases which are vacuolar or lysosomal membrane-associated proteins. Humans express four isoforms, ATP13A2 to ATP13A5
[2, 3]
.

SPF1 from yeast and ATP13A1 are ER translocases required to remove mitochondrial transmembrane proteins mistargeted to the endoplasmic reticulum
[13, 6]
. They were initially thought to mediate ion transport such as calcium or manganese but then it was reported that they specifically binds moderately hydrophobic transmembrane with short hydrophilic lumenal domains that misinsert into the endoplasmic reticulum
[13, 5, 8]
.

Human ATP13A2 (also known as PARK9), the most studied member of the P5B-type, is a neuroprotective ATPase enriched in the brain that selectively imports spermine ions from lysosomes into the cytosol
[4, 10, 9]
. Mutations ATP13A2 cause a rare monogenic form of juvenile-onset Parkinson's disease named Kufor-Rakeb syndrome and other neurodegenerative diseases
[7]
.

This entry includes also other isoforms such as ATP13A3, ATP13A4, ATP13A5.

P-ATPases (also known as E1-E2 ATPases) (
3.6.3.-
) are found in bacteria and in a number of eukaryotic plasma membranes and organelles
[1]
. P-ATPases function to transport a variety of different compounds, including ions and phospholipids, across a membrane using ATP hydrolysis for energy. There are many different classes of P-ATPases, which transport specific types of ion: H+, Na+, K+, Mg2+, Ca2+, Ag+and Ag2+, Zn2+, Co2+, Pb2+, Ni2+, Cd2+, Cu+and Cu2+. P-ATPases can be composed of one or two polypeptides, and can usually assume two main conformations called E1 and E2.

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.

References

1.Evolution of substrate specificities in the P-type ATPase superfamily. Axelsen KB, Palmgren MG. J. Mol. Evol. 46, 84-101, (1998). View articlePMID: 9419228

2.Structural basis of polyamine transport by human ATP13A2 (PARK9). Sim SI, von Bulow S, Hummer G, Park E. Mol Cell 81, 4635-4649.e8, (2021). PMID: 34715013

3.Structure and transport mechanism of P5B-ATPases. Li P, Wang K, Salustros N, Gronberg C, Gourdon P. Nat Commun 12, 3973, (2021). PMID: 34172751

4.Caenorhabditis elegans P5B-type ATPase CATP-5 operates in polyamine transport and is crucial for norspermidine-mediated suppression of RNA interference. Heinick A, Urban K, Roth S, Spies D, Nunes F, Phanstiel O 4th, Liebau E, Luersen K. FASEB J. 24, 206-17, (2010). PMID: 19762559

5.Shadows of an absent partner: ATP hydrolysis and phosphoenzyme turnover of the Spf1 (sensitivity to Pichia farinosa killer toxin) P5-ATPase. Corradi GR, de Tezanos Pinto F, Mazzitelli LR, Adamo HP. J Biol Chem 287, 30477-84, (2012). PMID: 22745129

6.Ergosterol content specifies targeting of tail-anchored proteins to mitochondrial outer membranes. Krumpe K, Frumkin I, Herzig Y, Rimon N, Ozbalci C, Brugger B, Rapaport D, Schuldiner M. Mol Biol Cell 23, 3927-35, (2012). PMID: 22918956

7.Structural mechanisms for gating and ion selectivity of the human polyamine transporter ATP13A2. Tillinghast J, Drury S, Bowser D, Benn A, Lee KPK. Mol Cell 81, 4650-4662.e4, (2021). PMID: 34715014

8.Reduction of the P5A-ATPase Spf1p phosphoenzyme by a Ca2+-dependent phosphatase. Corradi GR, Mazzitelli LR, Petrovich GD, Grenon P, Sorensen DM, Palmgren M, de Tezanos Pinto F, Adamo HP. PLoS One 15, e0232476, (2020). PMID: 32353073

9.ATP13A2 deficiency disrupts lysosomal polyamine export. van Veen S, Martin S, Van den Haute C, Benoy V, Lyons J, Vanhoutte R, Kahler JP, Decuypere JP, Gelders G, Lambie E, Zielich J, Swinnen JV, Annaert W, Agostinis P, Ghesquiere B, Verhelst S, Baekelandt V, Eggermont J, Vangheluwe P. Nature 578, 419-424, (2020). PMID: 31996848

10.ATP13A3 is a major component of the enigmatic mammalian polyamine transport system. Hamouda NN, Van den Haute C, Vanhoutte R, Sannerud R, Azfar M, Mayer R, Cortes Calabuig A, Swinnen JV, Agostinis P, Baekelandt V, Annaert W, Impens F, Verhelst SHL, Eggermont J, Martin S, Vangheluwe P. J Biol Chem 296, 100182, (2021). PMID: 33310703

11.Pleiotropic Effects of the P5-Type ATPase SpfA on Stress Response Networks Contribute to Virulence in the Pathogenic Mold Aspergillus fumigatus. Guirao-Abad JP, Weichert M, Luengo-Gil G, Sze Wah Wong S, Aimanianda V, Grisham C, Malev N, Reddy S, Woollett L, Askew DS. mBio 12, e0273521, (2021). PMID: 34663092

12.The Parkinson's disease-associated genes ATP13A2 and SYT11 regulate autophagy via a common pathway. Bento CF, Ashkenazi A, Jimenez-Sanchez M, Rubinsztein DC. Nat Commun 7, 11803, (2016). PMID: 27278822

13.The endoplasmic reticulum P5A-ATPase is a transmembrane helix dislocase. McKenna MJ, Sim SI, Ordureau A, Wei L, Harper JW, Shao S, Park E. Science 369, (2020). PMID: 32973005

Further reading

14. Mechanisms of ATPases--a multi-disciplinary approach. Rappas M, Niwa H, Zhang X. Curr. Protein Pept. Sci. 5, 89-105, (2004). View articlePMID: 15078220

15. F-type or V-type? The chimeric nature of the archaebacterial ATP synthase. Schafer G, Meyering-Vos M. Biochim. Biophys. Acta 1101, 232-5, (1992). PMID: 1385979

16. The evolution of A-, F-, and V-type ATP synthases and ATPases: reversals in function and changes in the H+/ATP coupling ratio. Cross RL, Muller V. FEBS Lett. 576, 1-4, (2004). View articlePMID: 15473999

17. F-and V-ATPases in the genus Thermus and related species. Radax C, Sigurdsson O, Hreggvidsson GO, Aichinger N, Gruber C, Kristjansson JK, Stan-Lotter H. Syst. Appl. Microbiol. 21, 12-22, (1998). PMID: 9741106

18. Regulation and isoform function of the V-ATPases. Toei M, Saum R, Forgac M. Biochemistry 49, 4715-23, (2010). View articlePMID: 20450191

19. New insights into structure-function relationships between archeal ATP synthase (A1A0) and vacuolar type ATPase (V1V0). Gruber G, Marshansky V. Bioessays 30, 1096-109, (2008). View articlePMID: 18937357

GO terms

biological process

  • None

cellular component

Cross References

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