SERCA, or sarcoplasmic/

endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...

Ca²⁺-

ATPase ATPases (, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, ATP hydrolase, adenosine triphosphatase) are a class of enzymes that catalyze the decomposition of ATP into ADP and a free phosphate ion or ...

, or SR Ca²⁺-

, is a calcium ATPase-type P-ATPase. Its major function is to transport calcium from the cytosol into the sarcoplasmic reticulum.

Function

SERCA is a

P-type ATPase The P-type ATPases, also known as E1-E2 ATPases, are a large group of evolutionarily related ion and lipid pumps that are found in bacteria, archaea, and eukaryotes. P-type ATPases are α-helical bundle primary transporters named based upon thei ...

. It resides in the sarcoplasmic reticulum (SR) within

myocyte A muscle cell, also known as a myocyte, is a mature contractile Cell (biology), cell in the muscle of an animal. In humans and other vertebrates there are three types: skeletal muscle, skeletal, smooth muscle, smooth, and Cardiac muscle, cardiac ...

s. It is a Ca²⁺ ATPase that transfers Ca²⁺ from the

cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...

of the cell to the lumen of the SR. This uses energy from ATP hydrolysis during muscle relaxation. There are 3 major domains on the cytoplasmic face of SERCA: the

phosphorylation In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writ ...

and nucleotide-binding domains, which form the catalytic site, and the actuator domain, which is involved in the transmission of major

conformational change In biochemistry, a conformational change is a change in the shape of a macromolecule, often induced by environmental factors. A macromolecule is usually flexible and dynamic. Its shape can change in response to changes in its environment or othe ...

s. In addition to its calcium-transporting functions, SERCA1 generates heat in

brown adipose tissue Brown adipose tissue (BAT) or brown fat makes up the adipose organ together with white adipose tissue (or white fat). Brown adipose tissue is found in almost all mammals. Classification of brown fat refers to two distinct cell populations with si ...

and in

skeletal muscle Skeletal muscle (commonly referred to as muscle) is one of the three types of vertebrate muscle tissue, the others being cardiac muscle and smooth muscle. They are part of the somatic nervous system, voluntary muscular system and typically are a ...

s. Along with the heat it naturally produces due to its inefficiency in pumping ions, when it binds to a regulator called sarcolipin it stops pumping and functions solely as an ATP hydrolase. This mechanism of thermogenesis is widespread in mammals and in

endotherm An endotherm (from Greek ἔνδον ''endon'' "within" and θέρμη ''thermē'' "heat") is an organism that maintains its body at a metabolically favorable temperature, largely by the use of heat released by its internal bodily functions inst ...

ic fishes.

Regulation

The rate at which SERCA moves Ca²⁺ across the SR membrane can be controlled by the regulatory protein phospholamban (PLB/PLN). SERCA is not as active when PLB is bound to it. 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. Activity regulation of SERCA can also involve phosphorylation of SERCA itself by interaction with GSK3β. Phosphorylation of SERCA2a at S663 was shown to reduce SERCA2a activity. 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 purposes, SERCA can be inhibited by thapsigargin and induced by istaroxime. SERCA function is upregulated in the skeletal muscle of rabbits and in rodent myocardium by thyroid hormones. This mechanism may contribute to the proarrhythmogenic effect of thyrotoxicosis.

Paralogs

There are 3 major paralogs, SERCA1-3, which are expressed at various levels in different cell types. * ATP2A1 – SERCA1 * ATP2A2 – SERCA2 * ATP2A3 – SERCA3 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.

References

External links

* {{ATPases Transmembrane proteins