Plasma membrane calcium-transporting ATPase 4 (PMCA4), isoform b (PMCA4b)

Plasma membrane calcium-transporting ATPase 4, isoform b (PMCA4b), is a member of the P-type ATPase family responsible for the high-affinity, active transport of calcium ions out of eukaryotic cells using energy from ATP hydrolysis[2][8]. The gene encoding PMCA4b is ATP2B4. PMCA4b is widely expressed and is subject to complex regulation via alternative splicing, interaction with calmodulin, and partner proteins, especially through its unique PDZ-binding motif present in the "b" isoform[1][3][4]. It plays a crucial role in maintaining low cytosolic Ca2+ concentration and is involved in fine-tuning signaling pathways controlling muscle contraction, neuronal activity, sperm function, cell migration, and shape. Pathogenic mutations lead to neurological disorders (familial spastic paraplegia) and male infertility has been reported in knockout models[1][2][5]. PMCA4b also inhibits melanoma cell migration and modulates nitric oxide synthase activity in the heart, linking it to cancer and cardiovascular physiology[1][10]. While PMCA4b has no specific approved drugs targeting it, its central role in Ca2+ signaling and disease makes it a potential therapeutic target[4].

Other names

Plasma membrane calcium ATPase isoform 4bATPase plasma membrane Ca2+ transporting 4bATP2B4 (gene name)PMCA4bPlasma membrane Ca2+ pump 4b

Inhibition of the pump impairs calcium extrusion, increases intracellular Ca2+, potentially disrupting cellular signaling[4].