Thrombomodulin

Thrombomodulin
PDB rendering based on 1adx.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1ADX, 1DQB, 1DX5, 1EGT, 1FGD, 1FGE, 1HLT, 1TMR, 1ZAQ, 2ADX, 3GIS
Identifiers
Symbols	THBD ; AHUS6; BDCA3; CD141; THPH12; THRM; TM
External IDs	OMIM: 188040 MGI: 98736 HomoloGene: 308 GeneCards: THBD Gene
Gene ontology Molecular function • receptor activity • transmembrane signaling receptor activity • calcium ion binding • protein binding Cellular component • extracellular space • plasma membrane • integral component of plasma membrane • cell surface Biological process • signal transduction • female pregnancy • blood coagulation • response to X-ray • negative regulation of platelet activation • negative regulation of blood coagulation • response to lipopolysaccharide • leukocyte migration • response to cAMP • negative regulation of fibrinolysis Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7056	21824
Ensembl	ENSG00000178726	ENSMUSG00000074743
UniProt	P07204	P15306
RefSeq (mRNA)	NM_000361	NM_009378
RefSeq (protein)	NP_000352	NP_033404
Location (UCSC)	Chr 20: 23.05 – 23.05 Mb	Chr 2: 148.4 – 148.41 Mb
PubMed search	[1]	[2]

Thrombomodulin (TM), CD141 or BDCA-3 is an integral membrane protein expressed on the surface of endothelial cells and serves as a cofactor for thrombin. It reduces blood coagulation by converting thrombin to an anticoagulant enzyme from a procoagulant enzyme. Thrombomodulin is also expressed on human mesothelial cell, monocyte and a dendritic cell subset.

Characterization

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.

Function

Thrombomodulin functions as a cofactor in the thrombin-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 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 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 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 cells called MDC2. Its function on these cells is unknown.

Interactions

Thrombomodulin has been shown to interact with thrombin.

External links

• GeneReviews/NCBI/NIH/UW entry on Atypical Hemolytic-Uremic Syndrome
• OMIM entries on Atypical Hemolytic-Uremic Syndrome