ATP2A1
Developmental stage
Isoform SERCA1A accounts for more than 99% of SERCA1 isoforms expressed in adult skeletal muscle, while isoform SERCA1B predominates in neo-natal skeletal muscle.
Domain
Ca(2+) and ATP binding cause major rearrangements of the cytoplasmic and transmembrane domains. According to the E1-E2 model, Ca(2+) binding to the cytosolic domain of the pump in the high-affinity E1 conformation is followed by the ATP-dependent phosphorylation of the active site Asp, giving rise to E1P. A conformational change of the phosphoenzyme gives rise to the low-affinity E2P state that exposes the Ca(2+) ions to the lumenal side and promotes Ca(2+) release. Dephosphorylation of the active site Asp mediates the subsequent return to the E1 conformation.
PLN and SLN both have a single transmembrane helix; both occupy a similar binding site on ATP2A1 that is situated between the ATP2A1 transmembrane helices.
Function
Key regulator of striated muscle performance by acting as the major Ca(2+) ATPase responsible for the reuptake of cytosolic Ca(2+) into the sarcoplasmic reticulum. Catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen (By similarity). Contributes to calcium sequestration involved in muscular excitation/contraction (PubMed:10914677).
Involvement in disease
Brody disease
BROD
An autosomal recessive muscular disorder characterized by exercise-induced muscle stiffness and cramps primarily affecting the arms, legs, and eyelids, although more generalized muscle involvement may also occur.
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 IIA subfamily.
Tissue Specificity
Skeletal muscle, fast twitch muscle (type II) fibers.
Cellular localization
- Endoplasmic reticulum membrane
- Multi-pass membrane protein
- Sarcoplasmic reticulum membrane
- Multi-pass membrane protein
Alternative names
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1, SERCA1, SR Ca(2+)-ATPase 1, Calcium pump 1, Endoplasmic reticulum class 1/2 Ca(2+) ATPase, ATP2A1