Thrombomodulin (TM),
CD141 or BDCA-3 is an
integral membrane protein
An integral, or intrinsic, membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane. All transmembrane proteins can be classified as IMPs, but not all IMPs are transmembrane proteins. IMPs comp ...
expressed on the surface of
endothelial cell
The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and th ...
s and serves as a cofactor for
thrombin
Prothrombin (coagulation factor II) is encoded in the human by the F2-gene. It is proteolytically cleaved during the clotting process by the prothrombinase enzyme complex to form thrombin.
Thrombin (Factor IIa) (, fibrose, thrombase, throm ...
. It reduces
blood coagulation
Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The process of coagulatio ...
by converting thrombin to an anticoagulant
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
from a procoagulant enzyme. Thrombomodulin is also expressed on human
mesothelial cell,
monocyte
Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and monocyte-derived dendritic cells. As a part of the vertebrate innate immune system monocytes also ...
and a
dendritic cell
A dendritic cell (DC) is an antigen-presenting cell (also known as an ''accessory cell'') of the mammalian immune system. A DC's main function is to process antigen material and present it on the cell surface to the T cells of the immune system ...
subset.
Genetics and structure
In humans, thrombomodulin is encoded by the
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
The protein has a molecular mass of 74k
Da, and consists of a single chain with six tandemly repeated
EGF-like domains, a
Serine
Serine
(symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α- amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − ...
/
Threonine
Threonine (symbol Thr or T) is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form when dissolved in water), a carboxyl group (which is in the deprotonated −COO− ...
-rich spacer and a
transmembrane
A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently u ...
domain.
It is a member of the
C-type lectin domain (CTLD) group 14 family.
Function
Thrombomodulin functions as a
cofactor in the
thrombin
Prothrombin (coagulation factor II) is encoded in the human by the F2-gene. It is proteolytically cleaved during the clotting process by the prothrombinase enzyme complex to form thrombin.
Thrombin (Factor IIa) (, fibrose, thrombase, throm ...
-induced activation of
protein C
Protein C, also known as autoprothrombin IIA and blood coagulation factor XIV, is a zymogen, that is, an inactive enzyme. The activated form plays an important role in regulating anticoagulation, inflammation, and cell death and maintaini ...
in the
anticoagulant
An anticoagulant, commonly known as a blood thinner, is a chemical substance that prevents or reduces the coagulation of blood, prolonging the clotting time. Some occur naturally in blood-eating animals, such as leeches and mosquitoes, which ...
pathway by forming a 1:1 stoichiometric complex with thrombin. This raises the speed of protein C activation thousandfold. Thrombomodulin-bound thrombin has procoagulant effect at the same time by inhibiting fibrinolysis by cleaving
thrombin-activatable fibrinolysis inhibitor (TAFI, aka carboxypeptidase B2) into its active form.
Thrombomodulin is a
glycoprotein
Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...
on the surface of endothelial cells that, in addition to binding thrombin, regulates
C3b inactivation by factor I. Mutations in the thrombomodulin gene (THBD) have also been reported to be associated with
atypical hemolytic-uremic syndrome (aHUS).
The
antigen
In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response.
...
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
A dendritic cell (DC) is an antigen-presenting cell (also known as an ''accessory cell'') of the mammalian immune system. A DC's main function is to process antigen material and present it on the cell surface to the T cells of the immune system ...
s called MDC2. Its function on these cells is unknown.
Interactions
Thrombomodulin has been shown to
interact with
thrombin
Prothrombin (coagulation factor II) is encoded in the human by the F2-gene. It is proteolytically cleaved during the clotting process by the prothrombinase enzyme complex to form thrombin.
Thrombin (Factor IIa) (, fibrose, thrombase, throm ...
.
References
Further reading
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External links
GeneReviews/NCBI/NIH/UW entry on Atypical Hemolytic-Uremic Syndrome OMIM entries on Atypical Hemolytic-Uremic Syndrome
{{Clusters of differentiation
Coagulation system
Clusters of differentiation