ATP2B1
Domain
Isoforms A, C, D and E contain an additional calmodulin-binding subdomain B which is different in the different splice variants and shows pH dependent calmodulin binding properties.
Function
Catalyzes the hydrolysis of ATP coupled with the transport of calcium from the cytoplasm to the extracellular space thereby maintaining intracellular calcium homeostasis (PubMed:35358416). 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 (PubMed:29104511). May play a role in synaptic transmission by modulating calcium and proton dynamics at the synaptic vesicles.
Involvement in disease
Intellectual developmental disorder, autosomal dominant 66
MRD66
An autosomal dominant disorder characterized by mild to moderate global development delay, impaired intellectual development, and speech delay. Additional common symptoms include autism, seizures, and distal limb abnormalities. Disease severity is highly variable.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIB subfamily.
Tissue Specificity
Isoform B: Ubiquitously expressed. Isoform C: Found in brain cortex, skeletal muscle and heart muscle. Isoform D: Has only been found in fetal skeletal muscle. Isoform K: Found in small intestine and liver. Abundantly expressed in the endometrial epithelial cells and glandular epithelial cells in early-proliferative phase and early-secretory phases (PubMed:21400627).
Cellular localization
- Cell membrane
- Multi-pass membrane protein
- Basolateral cell membrane
- Synapse
- Presynaptic cell membrane
- Multi-pass membrane protein
- Cytoplasmic vesicle
- Secretory vesicle
- Synaptic vesicle membrane
- Multi-pass membrane protein
- 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.
Alternative names
PMCA1, ATP2B1, Plasma membrane calcium-transporting ATPase 1, Plasma membrane calcium ATPase isoform 1, Plasma membrane calcium pump isoform 1