ATP2B4

Alternative Name: ATPase Plasma Membrane Calcium Transporting 4, PMCA4, Plasma Membrane Calcium-Transporting ATPase 4, PMCA4b, PMCA4x, Matrix-Remodeling-Associated Protein 1, Sarcolemmal Calcium Pump, EC 7.2.2.10, EC 3.6.3.8, EC 3.6.3

Description: ATP2B is a calcium pump that catalyzes the hydrolysis of ATP coupled with the transport of calcium from the cytoplasm to the extracellular space. It plays a critical role in intracellular calcium homeostasis by removing calcium ions from cells against very large concentration gradients. There are four isoforms of ATP2B (designated ATP2B1-4), and ATP2B4 is the most abundant form in mouse testis and sperm. ATP2B4 is localized to the principle piece of the sperm tail, which is also the location of CatSper, required for sperm hyperactivation. ATP2B4-null mice are infertile and sperm cannot achieve hyperactivated motility. The requirement for ATP2B4 and CatSper for hyperactivated motility and their co-expression in the sperm tail suggest they serve as the major calcium influx and efflux mechanism required for sperm hyperactivation. 5-(and-6)-carboxyeosin diacetate succinimidyl ester is known to inhibit ATP2B4.

Target

Product Details

User: Female, Male

Hormonal: No

Role in reproduction: Sperm Function

Multipurpose Preventive Technology (MPT): No

Status Details

Project Phase: Discovery and Early Development

Development Stage: Target Identification

Additional Information

References:
  • Calì, T., Brini, M., & Carafoli, E. (2018). The PMCA pumps in genetically determined neuronal pathologies. Neuroscience Letters,663, 2-11.

  • Jimenez-Gonzalez, C., Michelangeli, F., Harper, C., Barratt, C., & Publicover, S. (2005). Calcium signalling in human spermatozoa: A specialized ‘toolkit’ of channels, transporters and stores. Human Reproduction Update,12(3), 253-267.

  • Okunade, G. W., Miller, M. L., Pyne, G. J., Sutliff, R. L., Oconnor, K. T., Neumann, J. C., . . . Shull, G. E. (2004). Targeted Ablation of Plasma Membrane Ca2 -ATPase (PMCA) 1 and 4 Indicates a Major Housekeeping Function for PMCA1 and a Critical Role in Hyperactivated Sperm Motility and Male Fertility for PMCA4. Journal of Biological Chemistry,279(32), 33742-33750.

  • Schuh, K., Cartwright, E. J., Jankevics, E., Bundschu, K., Liebermann, J., Williams, J. C., . . . Neyses, L. (2004). Plasma Membrane Ca2 ATPase 4 Is Required for Sperm Motility and Male Fertility. Journal of Biological Chemistry,279(27), 28220-28226.

  • Calì, T., Brini, M., & Carafoli, E. (2018). The PMCA pumps in genetically determined neuronal pathologies. Neuroscience Letters,663, 2-11.

  • Wennemuth, G., Babcock, D. F., & Hille, B. (2003). Calcium Clearance Mechanisms of Mouse Sperm. The Journal of General Physiology,122(1), 115-128.

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