, or sarco/ endoplasmic reticulum Ca2+- ATPase
, or SR Ca2+- ATPase
, is a calcium ATPase
SERCA resides in the sarcoplasmic reticulum
(SR) within myocyte
s. It is a Ca2+ ATPase that transfers Ca2+ from the cytosol
of the cell to the lumen
of the SR at the expense of ATP hydrolysis
during muscle relaxation.
There are 3 major domains
on the cytoplasmic face of SERCA: the phosphorylation
and nucleotide-binding domains, which form the catalytic site
, and the actuator domain, which is involved in the transmission of major conformational change
It seems that, in addition to the calcium-transporting properties, SERCA1
generates heat in some adipocyte
s and can improve cold tolerance in some wood frogs
The rate at which SERCA moves Ca2+ across the SR membrane can be controlled by the regulatory protein phospholamban
(PLB/PLN). SERCA is normally inhibited by PLB, with which it is closely associated. Increased β-adrenergic
stimulation reduces the association between SERCA and PLB by the phosphorylation of PLB by PKA
. When PLB is associated with SERCA, the rate of Ca2+ movement is reduced; upon dissociation of PLB, Ca2+ movement increases.
Another protein, calsequestrin
, binds calcium within the SR and helps to reduce the concentration of free calcium within the SR, which assists SERCA so that it does not have to pump against such a high concentration gradient
. The SR has a much higher concentration of Ca2+ (10,000x) inside when compared to the cytoplasmic Ca2+ concentration. SERCA2 can be regulated by microRNAs, for instance miR-25 suppresses SERCA2 in heart failure.
For experimental reasons, SERCA can be inhibited by thapsigargin
and induced by istaroxime
There are 3 major paralogs
, SERCA1-3, which are expressed at various levels in different cell types.
There are additional post-translational isoforms of both SERCA2 and SERCA3, which serve to introduce the possibility of cell-type-specific Ca2+-reuptake responses as well as increasing the overall complexity of the Ca2+ signaling mechanism.