|
Gla Domain
Vitamin K-dependent carboxylation/gamma-carboxyglutamic (GLA) domain is a protein domain that contains post-translational modifications of many glutamate residues by vitamin K-dependent carboxylation to form γ-carboxyglutamate (Gla). Proteins with this domain are known informally as Gla proteins. The Gla residues are responsible for the high-affinity binding of calcium ions. The GLA domain binds calcium ions by chelating them between two carboxylic acid residues. These residues are part of a region that starts at the N-terminal extremity of the mature form of Gla proteins, and that ends with a conserved aromatic residue. This results in a conserved Gla-x(3)-Gla-x-Cys motif that is found in the middle of the domain, and which seems to be important for substrate recognition by the carboxylase. The 3D structures of several Gla domains have been solved. Calcium ions induce conformational changes in the Gla domain and are necessary for the Gla domain to fold properly. A common struct ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Coagulation Factor VIIa
Coagulation factor VII (, formerly known as proconvertin) is one of the proteins that causes blood to clot in the coagulation cascade, and in humans is coded for by the gene ''F7''. It is an enzyme of the serine protease class. Once bound to tissue factor released from damaged tissues, it is converted to factor VIIa (or ''blood-coagulation factor VIIa'', ''activated blood coagulation factor VII''), which in turn activates factor IX and factor X. Using genetic recombination a recombinant factor VIIa (eptacog alfa) (trade names include NovoSeven) has been approved by the FDA for the control of bleeding in hemophilia. It is sometimes used unlicensed in severe uncontrollable bleeding, although there have been safety concerns. A biosimilar form of recombinant activated factor VII (AryoSeven) is also available, but does not play any considerable role in the market. In April 2020, the US FDA approved a new rFVIIa product, eptacog beta (SEVENFACT), the first bypassing agent (BPA) app ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Factor X
Factor X, also known by the eponym Stuart–Prower factor, is an enzyme () of the coagulation cascade. It is a serine endopeptidase (protease group S1, PA clan). Factor X is synthesized in the liver and requires vitamin K for its synthesis. Factor X is activated, by hydrolysis, into factor Xa by both factor IX (with its cofactor, factor VIII in a complex known as ''intrinsic tenase'') and factor VII with its cofactor, tissue factor (a complex known as ''extrinsic tenase''). It is therefore the first member of the ''final common pathway'' or ''thrombin pathway''. It acts by cleaving prothrombin in two places (an arg- thr and then an arg-ile bond), which yields the active thrombin. This process is optimized when factor Xa is complexed with activated co-factor V in the prothrombinase complex. Factor Xa is inactivated by protein Z-dependent protease inhibitor (ZPI), a serine protease inhibitor (serpin). The affinity of this protein for factor Xa is increased 1000-fold by the p ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Inter-alpha-trypsin Inhibitor
Inter-alpha-trypsin inhibitors (IαI) are plasma proteins consisting of three of four heavy chains selected from the group ITIH1, ITIH2, ITIH3, ITIH4 and one light chain selected from the group AMBP or SPINT2. They function as protease inhibitors. IαI form complexes with hyaluronan (HA), generating a serum-derived hyaluronan-associated protein (SHAP)-HA complex. The SHAP-HA complex is found in very high concentration in rheumatoid arthritic synovial fluid Synovial fluid, also called synovia, elp 1/sup> is a viscous, non-Newtonian fluid found in the cavities of synovial joints. With its egg white–like consistency, the principal role of synovial fluid is to reduce friction between the articul ... suggesting it has a role in the inflammatory response. References External links * Protease inhibitors Human proteins Arthritis {{protein-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Transthyretin
Transthyretin (TTR or TBPA) is a transport protein in the plasma and cerebrospinal fluid that transports the thyroid hormone thyroxine (T4) and retinol to the liver. This is how transthyretin gained its name: ''transports thyroxine and retinol''. The liver secretes TTR into the blood, and the choroid plexus secretes TTR into the cerebrospinal fluid. TTR was originally called prealbumin (or thyroxine-binding prealbumin) because it migrated faster than albumin on electrophoresis gels. Prealbumin was felt to be a misleading name, it is not a synthetic precursor of albumin. The alternative name TTR was proposed by DeWitt Goodman in 1981. Transthyretin protein is encoded by the ''TTR'' gene located on the 18th chromosome. Binding affinities It functions in concert with two other thyroid hormone-binding proteins in the serum: In cerebrospinal fluid TTR is the primary carrier of T4. TTR also acts as a carrier of retinol (vitamin A) through its association with retinol-binding p ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Calcification
Calcification is the accumulation of calcium salts in a body tissue. It normally occurs in the formation of bone, but calcium can be deposited abnormally in soft tissue,Miller, J. D. Cardiovascular calcification: Orbicular origins. ''Nature Materials'' 12, 476-478 (2013). causing it to harden. Calcifications may be classified on whether there is mineral balance or not, and the location of the calcification. Calcification may also refer to the processes of normal mineral deposition in biological systems, such as the formation of stromatolites or mollusc shells (see Biomineralization). Signs and symptoms Calcification can manifest itself in many ways in the body depending on the location. In the pulpal structure of a tooth, calcification often presents asymptomatically, and is diagnosed as an incidental finding during radiographic interpretation. Individual teeth with calcified pulp will typically respond negatively to vitality testing; teeth with calcified pulp often lack se ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Matrix Gla Protein
Matrix Gla protein (MGP) is member of a family of vitamin K2 dependent, Gla-containing proteins. MGP has a high affinity binding to calcium ions, similar to other Gla-containing proteins. The protein acts as an inhibitor of vascular mineralization and plays a role in bone organization. MGP is found in a number of body tissues in mammals, birds, and fish. Its mRNA is present in bone, cartilage, heart, and kidney. It is present in bone together with the related vitamin K2-dependent protein osteocalcin. In bone, its production is increased by vitamin D. Genetics The ''MGP'' was linked to the short arm of chromosome 12 in 1990. Its mRNA sequence length is 585 bases long in humans. Physiology MGP and osteocalcin are both calcium-binding proteins that may participate in the organisation of bone tissue. Both have glutamate residues that are post-translationally carboxylated by the enzyme gamma-glutamyl carboxylase in a reaction that requires Vitamin K hydroquinone. Role in ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Bone Mineralization
Biomineralization, also written biomineralisation, is the process by which living organisms produce minerals, often to harden or stiffen existing tissues. Such tissues are called mineralized tissues. It is an extremely widespread phenomenon; all six taxonomic kingdoms contain members that are able to form minerals, and over 60 different minerals have been identified in organisms. Examples include silicates in algae and diatoms, carbonates in invertebrates, and calcium phosphates and carbonates in vertebrates. These minerals often form structural features such as sea shells and the bone in mammals and birds. Organisms have been producing mineralized skeletons for the past 550 million years. Calcium carbonates and calcium phosphates are usually crystalline, but silica organisms (sponges, diatoms...) are always non crystalline minerals. Other examples include copper, iron and gold deposits involving bacteria. Biologically formed minerals often have special uses such as magnetic ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Osteocalcin
Osteocalcin, also known as bone gamma-carboxyglutamic acid-containing protein (BGLAP), is a small (49-amino-acid) noncollagenous protein hormone found in bone and dentin, first identified as a calcium-binding protein. Because osteocalcin has gla domains, its synthesis is vitamin K dependent. In humans, osteocalcin is encoded by the ''BGLAP'' gene. Its receptors include GPRC6A, GPR158, and possibly a third, yet-to-be-identified receptor. There is evidence that GPR37 might be the third osteocalcin receptor. Function Osteocalcin is secreted solely by osteoblasts and thought to play a role in the body's metabolic regulation. In its carboxylated form it binds calcium directly and thus concentrates in bone. In its uncarboxylated form, osteocalcin acts as a hormone in the body, signalling in the pancreas, fat, muscle, testes, and brain. * In the pancreas, osteocalcin acts on beta cells, causing beta cells in the pancreas to release more insulin. * In fat cells, osteocalcin tr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protein Z
Protein Z (PZ or PROZ) is a Protein in humans which is encoded by the ''PROZ'' gene. Protein Z is a member of the coagulation cascade, the group of blood proteins that leads to the formation of blood clots. It is a glycoprotein. Protein Z functions to inhibit blood coagulation by binding to an inhibitor. It is a GLA domain protein and thus Vitamin K-dependent, and its functionality is therefore impaired in warfarin therapy. Physiology Although it is not enzymatically active, it is structurally related to several serine proteases of the coagulation cascade: Factors VII, IX, X and Protein C. The carboxyglutamate residues (which require Vitamin K) bind Protein Z to phospholipid surfaces. The main role of Protein Z appears to be the degradation of Factor Xa. This is done by Protein Z-related protease inhibitor (ZPI), but the reaction is accelerated 1000-fold by the presence of Protein Z. Oddly, ZPI also degrades Factor XI, but this reaction does not require the presence of Pr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protein S
Protein S (also known as PROS) is a vitamin K-dependent plasma glycoprotein synthesized in the liver. In the circulation, Protein S exists in two forms: a free form and a complex form bound to complement protein C4b-binding protein (C4BP). In humans, protein S is encoded by the ''PROS1'' gene. Protein S plays a role in coagulation. History Protein S is named for Seattle, Washington, where it was originally discovered and purified by Earl Davie's group in 1977. Structure Protein S is partly homologous to other vitamin K-dependent plasma coagulation proteins, such as protein C and factors VII, IX, and X. Similar to them, it has a Gla domain and several EGF-like domains (four rather than two), but no serine protease domain. Instead, there is a large C-terminus domain that is homologous to plasma steroid hormone-binding proteins such as sex hormone-binding globulin and corticosteroid-binding globulin. It may play a role in the protein functions as either a cofactor for activated ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Vascular Permeability
Vascular permeability, often in the form of capillary permeability or microvascular permeability, characterizes the capacity of a blood vessel wall to allow for the flow of small molecules (drugs, nutrients, water, ions) or even whole cells (lymphocytes on their way to the site of inflammation) in and out of the vessel. Blood vessel walls are lined by a single layer of endothelial cells. The gaps between endothelial cells ( cell junctions) are strictly regulated depending on the type and physiological state of the tissue. There are several techniques to measure vascular permeability to certain molecules. For instance, the cannulation of a single microvessel with a micropipette, the microvessel is perfused with a certain pressure, occluded downstream and then the velocity of some cells will be related to the permeability.Michel, C. C., Mason, J. C., Curry, F. E. & Tooke, J. E. Development of Landis Technique for Measuring Filtration Coefficient of Individual Capillaries in Frog ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cell Death
Cell death is the event of a biological cell ceasing to carry out its functions. This may be the result of the natural process of old cells dying and being replaced by new ones, as in programmed cell death, or may result from factors such as diseases, localized injury, or the death of the organism of which the cells are part. Apoptosis or Type I cell-death, and autophagy or Type II cell-death are both forms of programmed cell death, while necrosis is a non-physiological process that occurs as a result of infection or injury. Programmed cell death Programmed cell death (PCD) is cell death mediated by an intracellular program. PCD is carried out in a regulated process, which usually confers advantage during an organism's life-cycle. For example, the differentiation of fingers and toes in a developing human embryo occurs because cells between the fingers apoptose; the result is that the digits separate. PCD serves fundamental functions during both plant and metazoa (multicel ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
_effect.png "Click for more on -> Vascular Permeability")
