SERCA, or sarco/

endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ...

Ca²⁺-

ATPase ATPases (, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, SV40 T-antigen, ATP hydrolase, complex V (mitochondrial electron transport), (Ca2+ + Mg2+)-ATPase, HCO3−-ATPase, adenosine triphosphatase) are ...

, 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. It resides in the

sarcoplasmic reticulum The sarcoplasmic reticulum (SR) is a membrane-bound structure found within muscle cells that is similar to the smooth endoplasmic reticulum in other cells. The main function of the SR is to store calcium ions (Ca2+). Calcium ion levels are ke ...

(SR) within

myocyte A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell (cardiomyocyte), or a smooth muscle cell as these are both small cells. A skeletal muscle cell is long and threadlike with many nuclei and is called a mus ...

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 ATP hydrolysis is the catabolic reaction process by which chemical energy that has been stored in the high-energy phosphoanhydride bonds in adenosine triphosphate (ATP) is released after splitting these bonds, for example in muscles, by prod ...

during muscle relaxation. There are 3 major domains on the cytoplasmic face of SERCA: the

phosphorylation In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...

and nucleotide-binding domains, which form the

catalytic site In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate (binding site) a ...

, 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 oth ...

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 muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of m ...

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 The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like bet ...

stimulation reduces the association between SERCA and PLB by the phosphorylation of PLB by

PKA PKA may refer to: * Professionally known as: ** Pen name ** Stage persona * p''K''a, the symbol for the acid dissociation constant at logarithmic scale * Protein kinase A, a class of cAMP-dependent enzymes * Pi Kappa Alpha, the North-American so ...

. When PLB is associated with SERCA, the rate of Ca²⁺ movement is reduced; upon dissociation of PLB, Ca²⁺ movement increases. Another protein,

calsequestrin Calsequestrin is a calcium-binding protein that acts as a calcium buffer within the sarcoplasmic reticulum. The protein helps hold calcium in the cisterna of the sarcoplasmic reticulum after a muscle contraction, even though the concentration ...

, 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 Molecular diffusion, often simply called diffusion, is the thermal motion of all (liquid or gas) particles at temperatures above absolute zero. The rate of this movement is a function of temperature, viscosity of the fluid and the size (mass) ...

. 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 ATP2A2 also known as sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) is an ATPase associated with Darier's disease and Acrokeratosis verruciformis. This gene encodes one of the SERCA Ca(2+)-ATPases, which are intracellular pumps loc ...

– 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