Thrombomodulin
Encyclopedia
Thrombomodulin, CD
141 or BDCA-3 is an integral membrane protein
expressed on the surface of endothelial cells. In humans, thrombomodulin is encoded by the THBD gene
. The protein has a molecular mass of 74kDa, and consists of a single chain with 5 distinct domains
.
-induced activation of protein C
in the anticoagulant
pathway by forming a 1:1 stoichiometric complex with thrombin. This raises the speed of protein C activation thousandfold. Thrombomodulin-bound thrombin has no procoagulant effect. The TT-complex also inhibits fibrinolysis by cleaving thrombin-activatable fibrinolysis inhibitor (TAFI) into its active form.
The antigen
described as BDCA-3 has turned out to be identical to thrombomodulin. Thus, it was revealed that this molecule also occurs on a very rare (0.02%) subset of human dendritic cell
s called MDC2. Its function on these cells is unknown at present, but apparently, thrombomodulin has at least one other ligand
apart from thrombin, because anticoaglulation is a commonplace function, in contrast to the rarity of MDC2 cells.
with Thrombin
.
Cluster of differentiation
The cluster of differentiation is a protocol used for the identification and investigation of cell surface molecules present on white blood cells, providing targets for immunophenotyping of cells...
141 or BDCA-3 is an integral membrane protein
Integral membrane protein
An integral membrane protein is a protein molecule that is permanently attached to the biological membrane. Proteins that cross the membrane are surrounded by "annular" lipids, which are defined as lipids that are in direct contact with a membrane protein...
expressed on the surface of endothelial cells. In humans, thrombomodulin is encoded by the THBD gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. The protein has a molecular mass of 74kDa, and consists of a single chain with 5 distinct domains
Protein domain
A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...
.
Function
Thrombomodulin functions as a cofactor in the thrombinThrombin
Thrombin is a "trypsin-like" serine protease protein that in humans is encoded by the F2 gene. Prothrombin is proteolytically cleaved to form thrombin in the first step of the coagulation cascade, which ultimately results in the stemming of blood loss...
-induced activation of protein C
Protein C
Protein C, also known as autoprothrombin IIA and blood coagulation factor XIV, is a zymogenic protein, the activated form of which plays an important role in regulating blood clotting, inflammation, cell death and maintaining the permeability of blood vessel walls in humans and other animals...
in the anticoagulant
Anticoagulant
An anticoagulant is a substance that prevents coagulation of blood. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic disorders. Some anticoagulants are used in medical equipment, such as test tubes, blood transfusion bags, and renal dialysis...
pathway by forming a 1:1 stoichiometric complex with thrombin. This raises the speed of protein C activation thousandfold. Thrombomodulin-bound thrombin has no procoagulant effect. The TT-complex also inhibits fibrinolysis by cleaving thrombin-activatable fibrinolysis inhibitor (TAFI) into its active form.
The antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
described as BDCA-3 has turned out to be identical to thrombomodulin. Thus, it was revealed that this molecule also occurs on a very rare (0.02%) subset of human dendritic cell
Dendritic cell
Dendritic cells are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells...
s called MDC2. Its function on these cells is unknown at present, but apparently, thrombomodulin has at least one other ligand
Ligand (biochemistry)
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as ionic bonds, hydrogen...
apart from thrombin, because anticoaglulation is a commonplace function, in contrast to the rarity of MDC2 cells.
Interactions
Thrombomodulin has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with Thrombin
Thrombin
Thrombin is a "trypsin-like" serine protease protein that in humans is encoded by the F2 gene. Prothrombin is proteolytically cleaved to form thrombin in the first step of the coagulation cascade, which ultimately results in the stemming of blood loss...
.