Polyamine-transporting ATPase 13A3 (ATP13A3) (ATP13A3)

Polyamine-transporting ATPase 13A3 (ATP13A3) is a P5B-type transport ATPase that serves as a primary component of the mammalian polyamine transport system, mediating the uptake of putrescine, spermidine, and spermine [5, 11, 12]. It is localized to the membranes of early and recycling endosomes, where it facilitates the translocation of polyamines from the endolysosomal lumen into the cytosol to maintain cellular homeostasis [1, 14]. This transport activity is essential for cell proliferation, survival, and the maintenance of vascular endothelial integrity [1, 14]. Genetic loss-of-function variants in ATP13A3 are a major cause of heritable pulmonary arterial hypertension (PAH), as the resulting polyamine deficiency leads to endothelial dysfunction and vascular remodeling [1, 7, 14]. Conversely, ATP13A3 is often overexpressed in cancers such as neuroblastoma and pancreatic cancer, where it acts as a survival mechanism by importing extracellular polyamines, particularly when intracellular biosynthesis is inhibited by drugs like difluoromethylornithine (DFMO) [10, 13, 19]. Consequently, ATP13A3 is an emerging therapeutic target; polyamine transport inhibitors such as AMXT 1501 are being evaluated in clinical trials for cancer, while strategies to restore its function are being explored for the treatment of PAH [13, 17, 19].

Other names

AFURS1ATPase 13A3Putrescine transporting ATPasePPH5ATPase family homolog up-regulated in senescence cells 1Probable cation-transporting ATPase 13A3

Inhibition of ATP13A3-mediated polyamine uptake to suppress tumor growth in cancer; restoration of polyamine transport function to alleviate endothelial dysfunction in pulmonary arterial hypertension [1, 13, 14].