SERCA
Encyclopedia
SERCA, or sarco/endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...

 Ca
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...

2+-ATPase
ATPase
ATPases are a class of enzymes that catalyze the decomposition of adenosine triphosphate into adenosine diphosphate and a free phosphate ion. This dephosphorylation reaction releases energy, which the enzyme harnesses to drive other chemical reactions that would not otherwise occur...

, or SR Ca
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...

2+-ATPase
ATPase
ATPases are a class of enzymes that catalyze the decomposition of adenosine triphosphate into adenosine diphosphate and a free phosphate ion. This dephosphorylation reaction releases energy, which the enzyme harnesses to drive other chemical reactions that would not otherwise occur...

, is a calcium ATPase
Calcium ATPase
Calcium ATPase is a form of P-ATPase that transfers calcium after a muscle has contracted. The calcium ATPase are:*Plasma membrane Ca2+ ATPase *Sarcoplasmic reticulum Ca2+ ATPase - Plasma membrane Ca2+ ATPase :...

-type P-ATPase.

Function

SERCA resides in the sarcoplasmic reticulum (SR) within muscle cells. It is a Ca2+ ATPase that transfers Ca2+ from the cytosol
Cytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....

 of the cell to the lumen
Lumen (anatomy)
A lumen in biology is the inside space of a tubular structure, such as an artery or intestine...

 of the SR at the expense of ATP hydrolysis
ATP hydrolysis
ATP hydrolysis is the reaction by which chemical energy that has been stored and transported in the high-energy phosphoanhydridic bonds in ATP is released, for example in the muscles, to produce work. The product is ADP and an inorganic phosphate, orthophosphate...

 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 changes.

It seems that, in addition to the calcium-transporting properties, SERCA1
ATP2A1
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 is an enzyme that in humans is encoded by the ATP2A1 gene.-Interactions:ATP2A1 has been shown to interact with PLN and SLN.-Further reading:...

 generates heat in some adipocyte
Adipocyte
However, in some reports and textbooks, the number of fat cell increased in childhood and adolescence. The total number is constant in both obese and lean adult...

s.

Regulation

SERCA is normally inhibited by the defective phosphorylation of protein phospholamban
Phospholamban
Phospholamban, also known as PLN, is a protein that in humans is encoded by the PLN gene. Phospholamban is a 52-amino acid integral membrane protein that regulates the Ca2+ pump in cardiac muscle and skeletal muscle cells.- Function :...

, with which it is closely associated.
Another protein, calsequestrin
Calsequestrin
Calsequestrin is a calcium-binding protein of the sarcoplasmic reticulum. The protein helps hold calcium in the cisterna of the sarcoplasmic reticulum after a muscle contraction, even though the concentration of calcium in the sarcoplasmic reticulum is much higher than in the cytosol. It also...

, 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 intracellular Ca2+ concentration.

The rate at which SERCA moves Ca2+ across the SR membrane can be controlled by phospholamban
Phospholamban
Phospholamban, also known as PLN, is a protein that in humans is encoded by the PLN gene. Phospholamban is a 52-amino acid integral membrane protein that regulates the Ca2+ pump in cardiac muscle and skeletal muscle cells.- Function :...

 (PLB/PLN) under β-adrenergic stimulation. When PLB is associated with SERCA, the rate of Ca2+ movement is reduced, upon dissociation of PLB Ca2+ movement increases.

Paralogs

There are 3 major paralogs, SERCA1-3, which are expressed at various levels in different cell types.
  • ATP2A1
    ATP2A1
    Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 is an enzyme that in humans is encoded by the ATP2A1 gene.-Interactions:ATP2A1 has been shown to interact with PLN and SLN.-Further reading:...

     - SERCA1
  • ATP2A2
    ATP2A2
    ATP2A2 is an ATPase associated with Darier's disease and Acrokeratosis verruciformis.This gene encodes one of the SERCA Ca-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of muscle cells...

     - SERCA2
  • ATP2A3
    ATP2A3
    Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 is an enzyme that in humans is encoded by the ATP2A3 gene.-Further reading:...

    - 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.
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