Thrombomodulin

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.

THBD
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1ADX, 1DQB, 1DX5, 1EGT, 1FGD, 1FGE, 1HLT, 1TMR, 1ZAQ, 2ADX, 3GIS
Identifiers
Aliases	THBD, AHUS6, BDCA3, CD141, THPH12, THRM, TM, thrombomodulin, BDCA-3
External IDs	OMIM: 188040; MGI: 98736; HomoloGene: 308; GeneCards: THBD; OMA:THBD - orthologs
Gene location (Human) Chr. Chromosome 20 (human) Band 20p11.21 Start 23,045,633 bp End 23,049,672 bp
Gene location (Mouse) Chr. Chromosome 2 (mouse) Band 2 G3|2 73.45 cM Start 148,246,386 bp End 148,250,108 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gingival epithelium vena cava right lung skin of hip skin of abdomen skin of thigh periodontal fiber lower lobe of lung upper lobe of left lung left coronary artery Top expressed in right lung lobe left lung left lung lobe calvaria Gonadal ridge ankle aortic valve ascending aorta white adipose tissue decidua More reference expression data BioGPS More reference expression data
Gene ontology Molecular function calcium ion binding protein binding transmembrane signaling receptor activity signaling receptor activity Cellular component integral component of membrane cell surface plasma membrane integral component of plasma membrane membrane apicolateral plasma membrane vacuolar membrane extracellular space Biological process hemostasis female pregnancy negative regulation of platelet activation response to lipopolysaccharide response to cAMP negative regulation of fibrinolysis blood coagulation response to X-ray signal transduction negative regulation of blood coagulation leukocyte migration Sources:Amigo / QuickGO
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: 148.25 – 148.25 Mb PubMed search
Wikidata
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Genetics and structure

In humans, thrombomodulin is encoded by the THBD gene. The protein has a molecular mass of 74kDa, and consists of a single chain with six tandemly repeated EGF-like domains, a Serine/Threonine-rich spacer and a transmembrane domain. It is a member of the C-type lectin domain (CTLD) group 14 family.

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.^{[citation needed]}

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.^{[citation needed]}

Interactions

Thrombomodulin has been shown to interact with thrombin.