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SERCA
SERCA, or sarcoplasmic/endoplasmic reticulum Ca2+-ATPase, or SR Ca2+-ATPase, 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 (SR) within myocytes. It is a Ca2+ ATPase that transfers Ca2+ from the cytosol 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 and nucleotide-binding domains, which form the catalytic site, and the actuator domain, which is involved in the transmission of major conformational changes. In addition to its calcium-transporting functions, SERCA1 generates heat in brown adipose tissue and in skeletal muscles. 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 s ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 their ability to catalyze auto- (or self-) phosphorylation (hence P) of a key conserved aspartate residue within the pump and their energy source, adenosine triphosphate (ATP). In addition, they all appear to interconvert between at least two different conformations, denoted by E1 and E2. P-type ATPases fall under the P-type ATPase (P-ATPase) SuperfamilyTC# 3.A.3 which, as of early 2016, includes 20 different protein families. Most members of this transporter superfamily catalyze cation uptake and/or efflux, however one subfamily, the flippases,TC# 3.A.3.8 is involved in flipping phospholipids to maintain the asymmetric nature of the biomembrane. In humans, P-type ATPases serve as a basis for nerve impulses, relaxation of muscles, secre ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ATP2A3
Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 is an enzyme that in humans is encoded by the ''ATP2A3'' gene. This gene encodes one of the SERCA Ca2+-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of cells. SERCA3 expression was originally described as non-muscular, but was recently observed in cardiomyocyte. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen, and is involved in calcium sequestration associated with muscular excitation and contraction. Alternative splicing results in 6 transcript variants encoding different isoforms named SERCA3a to SERCA3f. Cancer ATP2A3 gene has been observed progressively downregulated in Human papillomavirus Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two year ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ATP2A1
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 (SERCA1) also known as Calcium pump 1, is an enzyme that in humans is encoded by the ''ATP2A1'' gene. Function This gene encodes one of the SERCA Ca2+-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of muscle cells. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen, and is involved in muscular excitation and contraction. Clinical significance Mutations in this gene cause some autosomal recessive forms of Brody disease, characterized by increasing impairment of muscular relaxation during exercise. Alternative splicing results in two transcript variants encoding different isoforms. Alternative splicing of ATP2A1 is also implicated in myotonic dystrophy type 1. ATP2A1 SERCA pumps were very strongly down regulated in amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS), al ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Istaroxime
Istaroxime is an investigational drug under development for treatment of acute decompensated heart failure Originally patented and developed by Sigma-Tau, it was sold to CVie Therapeutics in July 2012. Heart failure Istaroxime is a treatment for both systolic and diastolic heart failure. * Systolic heart failure is characterized by impaired ventricular emptying, caused by reduced contractility. * Diastolic dysfunction is defined by defective ventricular filling, caused by the heart's inability to properly relax between beats. Intracellular calcium fluxes regulate both contraction and relaxation. Cardiac muscle cells from patients with heart failure show smaller amounts of peak calcium in their cytoplasm during contraction, and slower removal., The mishandling of intracellular calcium is often due to problems in the cells’ ability to mediate calcium influx, and sequestration of calcium back in the sarcoplasmic reticulum., Mechanism of action Istaroxime is a positive ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sarcolipin
Sarcolipin is a micropeptide protein that in humans is encoded by the ''SLN'' gene. Function Sarcoplasmic reticulum Ca2+-ATPases are transmembrane proteins that catalyze the ATP-dependent transport of Ca2+ from the cytosol into the lumen of the sarcoplasmic reticulum in muscle cells. The SLN gene encodes a small transmembrane proteolipid that regulates several sarcoplasmic reticulum Ca2+-ATPases by reducing the accumulation of Ca2+ in the sarcoplasmic reticulum without affecting the rate of ATP hydrolysis. Ablation of sarcolipin increases atrial Ca2+ transient amplitudes and enhanced atrial contractility. Furthermore, atria from sarcolipin- null mice have blunted response to isoproterenol stimulation, implicating sarcolipin as a mediator of beta-adrenergic responses in atria. Sarcolipin is an important mediator of muscle based non shivering thermogenesis (NST). It causes the sarcoplasmic reticulum Ca2+-ATPases to stop pumping Ca2+ ions but continue futilely hydrolysing ATP ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 kept relatively constant, with the concentration of calcium ions within a cell being 10,000 times smaller than the concentration of calcium ions outside the cell. This means that small increases in calcium ions within the cell are easily detected and can bring about important cellular changes (the calcium is said to be a second messenger). Calcium is used to make calcium carbonate (found in chalk) and calcium phosphate, two compounds that the body uses to make teeth and bones. This means that too much calcium within the cells can lead to hardening (calcification) of certain intracellular structures, including the mitochondria, leading to cell death. Therefore, it is vital that calcium ion levels are controlled tightly, and can be released int ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phospholamban
Phospholamban, also known as PLN or PLB, is a micropeptide protein that in humans is encoded by the ''PLN'' gene. Phospholamban is a 52-amino acid integral membrane protein that regulates the calcium (Ca2+) pump in cardiac muscle cells. Function This protein is found as a pentamer and is a major substrate for the cAMP-dependent protein kinase (PKA) in cardiac muscle. In the unphosphorylated state, phospholamban is an inhibitor of cardiac muscle sarcoplasmic reticulum Ca2+-ATPase ( SERCA2) which transports calcium from cytosol into the sarcoplasmic reticulum. When phosphorylated (by PKA) - disinhibition of Ca2+-ATPase of SR leads to faster Ca2+ uptake into the sarcoplasmic reticulum, thereby contributing to the lusitropic response elicited in heart by beta-agonists. The protein is a key regulator of cardiac diastolic function. Mutations in this gene are a cause of inherited human dilated cardiomyopathy with refractory congestive heart failure. When phospholamban is phosp ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Thapsigargin
Thapsigargin is a non-competitive inhibitor of the sarco/endoplasmic reticulum Ca2+ ATPase ( SERCA). Structurally, thapsigargin is classified as a guaianolide, and is extracted from a plant, '' Thapsia garganica''. It is a tumor promoter in mammalian cells. Thapsigargin raises cytosolic (intracellular) calcium concentration by blocking the ability of the cell to pump calcium into the sarcoplasmic and endoplasmic reticula. Store-depletion can secondarily activate plasma membrane calcium channels, allowing an influx of calcium into the cytosol. Depletion of ER calcium stores leads to ER stress and activation of the unfolded protein response The unfolded protein response (UPR) is a cellular stress response related to the endoplasmic reticulum (ER) stress. It has been found to be conserved between mammalian species, as well as yeast and worm organisms. The UPR is activated in response t .... Non-resolved ER stress can cumulatively lead to cell death. Prolonged store depletion c ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 located in the sarcoplasmic or endoplasmic reticula The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for "little n ... of muscle cells. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen, and is involved in calcium sequestration associated with muscular excitation and contraction. Alternative splicing results in multiple transcript variants encoding different isoforms. References External links * {{ATPases ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 attached by tendons to bones of a skeleton. The skeletal muscle cells are much longer than in the other types of muscle tissue, and are also known as ''muscle fibers''. The tissue of a skeletal muscle is striated muscle tissue, striated – having a striped appearance due to the arrangement of the sarcomeres. A skeletal muscle contains multiple muscle fascicle, fascicles – bundles of muscle fibers. Each individual fiber and each muscle is surrounded by a type of connective tissue layer of fascia. Muscle fibers are formed from the cell fusion, fusion of developmental myoblasts in a process known as myogenesis resulting in long multinucleated cells. In these cells, the cell nucleus, nuclei, termed ''myonuclei'', are located along the inside ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Glycogen Synthase Kinase-3 Beta
Glycogen synthase kinase-3 beta, (GSK-3 beta), is an enzyme that in humans is encoded by the ''GSK3B'' gene. In mice, the enzyme is encoded by the Gsk3b gene. Abnormal regulation and expression of GSK-3 beta is associated with an increased susceptibility towards bipolar disorder. Function Glycogen synthase kinase-3 (GSK-3) is a proline-directed Serine/threonine-specific protein kinase, serine-threonine kinase that was initially identified as a phosphorylation, phosphorylating and an inactivating agent of glycogen synthase. Two isoforms, alpha (GSK3A) and beta, show a high degree of amino acid homology. GSK3B is involved in energy metabolism, neuronal cell development, and body pattern formation. It might be a new therapeutic target for ischemic stroke. Disease relevance Homozygous disruption of the Gsk3b locus in mice results in embryonic lethality during mid-gestation. This lethality phenotype could be rescued by inhibition of tumor necrosis factor. Two SNPs at this ge ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 (cardiomyocytes). A skeletal muscle cell is long and threadlike with multinucleated, many nuclei and is called a ''muscle fiber''. Muscle cells develop from embryonic precursor cells called myoblasts. Skeletal muscle cells form by cell fusion, fusion of myoblasts to produce multinucleated cells (syncytium, syncytia) in a process known as myogenesis. Skeletal muscle cells and cardiac muscle cells both contain myofibrils and sarcomeres and form a striated muscle tissue. Cardiac muscle cells form the cardiac muscle in the walls of the heart chambers, and have a single central Cell nucleus, nucleus. Cardiac muscle cells are joined to neighboring cells by intercalated discs, and when joined in a visible unit they are described as a ''cardiac m ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
