Catalyzes the hydrolysis of ATP coupled with the transport of calcium from the cytoplasm to the extracellular space thereby maintaining intracellular calcium homeostasis. Plays a role in blood pressure regulation through regulation of intracellular calcium concentration and nitric oxide production leading to regulation of vascular smooth muscle cells vasoconstriction. Positively regulates bone mineralization through absorption of calcium from the intestine. Plays dual roles in osteoclast differentiation and survival by regulating RANKL-induced calcium oscillations in preosteoclasts and mediating calcium extrusion in mature osteoclasts (By similarity). Regulates insulin sensitivity through calcium/calmodulin signaling pathway by regulating AKT1 activation and NOS3 activation in endothelial cells (By similarity). May play a role in synaptic transmission by modulating calcium and proton dynamics at the synaptic vesicles. ATP + Ca(2+)(in) + H2O = ADP + Ca(2+)(out) + H(+) + phosphate Monomer. Dimer. Oligomer. Calmodulin binding. Interacts with PDZD11. Interacts with SLC35G1 and STIM1. Interacts with YWHAE; interacts with the monomeric and dimeric forms of the YWHAE but prefer the monomer form; this interaction inhibits calcium-transporting ATPase activity (By similarity). Interacts with NPTN; this interaction stabilizes ATP2B1 and increases ATPase activity; this interaction controls T cell calcium homeostasis following T cell activation. Interacts with EPB41; regulates small intestinal calcium absorption through regulation of membrane expression of ATP2B1 (By similarity). Colocalizes with SV2A in photoreceptor synaptic terminals. Colocalizes with NPTN to the immunological synapse. Colocalizes with EPB41 to the basolateral membrane in enterocyte. Preferentially sorted to recycling synaptic vesicles. Isoform B is ubiquitously expressed and is the most predominant isoform. Isoform C is expressed at much lower levels in all tissues tested, but liver, while isoform A is found only in aorta, brain and stomach. Isoforms A and C contain and additional calmodulin-binding subdomain B which is different in the different splice variants and shows pH dependent calmodulin binding properties. Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIB subfamily.