|CD141||THBD(Thrombomodulin), TM, fetomodulin|
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Non-lineage Restricted Molecule|
Type 1 glycoprotein
|75 / 75|
105 / 105
|CD141 is expressed on endothelial cells, keratinocytes, megakaryocytes, platelets, monocytes, neutrophils, smooth muscle cells and synovial lining cells. Expression is on myeloid cells, blood vessels and lymphatic mesothelial cells and syncytiotrophoblasts.|
|MOLECULAR FAMIULY NAME: Belongs to the C-type lectin family.|
CD141 is a single-chain type-1 575 aa glycoprotein. It contains a 21 aa signal peptide, a 223 aa terminal ligand-binding extracellular domain which contains a N-terminal C-type lectin domain and 6 236 aa epidermal growth factor (EGF-like) domains, a 23 aa transmembrane membrane-spanning domain which contains potential O-glycosylation sites and a glycosaminoglycan attachment site and a short 38 aa cytoplasmic tail containing potential phosphorylation sites. There is a 34 aa serine/threonine-rich segment that is sometimes attached to a chondroitin sulfate (CS) moiety which is important for optimal anti-coagulant function.
CD141 gene has no introns.
There are N-linked glycosylation lectin-like and EGF domains, B-hydroxylation of asparagine residues EGF domains and O-linked glycosylation serine/threonine rich regions. CD141 exists in 2 major glycoforms, possessing or lacking a sulfate glycosaminoglycan (GAG) which is attached to the Ser/Thr region. Arterial endothelial cells express a higher proportion GAG-containing CD141 than venous endothelial cells.
| LIGANDS AND MOLECULES ASSOCIATED WITH CD141 |
|CD141 binds thrombin at the 5th and 6th EGF-like domains in the extracellular domain, inhibiting its fibrinolytic activity. CD141 with bound thrombin then binds protein C at the 3rd and 4th EGF-like domain and the thrombin than activates protein C. The NH2-terminal C-type lectin-like domain, whose function is unknown, may mediate endoctyosis of CD141 in vitro. CD141 is critical for the activation of protein C and initiation of the protein C anti-coagulant pathway. Via TAFI activation, this may be important fibrinolytic inhibitor.|
CD141 is a co-factor for the thrombin-mediated activation of protein C and is a co-factor for thrombin-activation of TAFI, which allows cleavage of C-terminal lysines from fibrin and consequently has decreased activation of plasminogen to plasmin.
DISEASE RELEVANCE AND FUNCTION OF CD141 IN INTACT ANIMAL
Defects in CD141 may be associated with an increased risk of thrombosis. CD141 changes the pro-coagulant thrombin into an anti-coagulant. Plasma CD141 levels are a potential marker for endothelial damage. Plasma CD141 is increased in diabetes mellitus and SLE and disseminated intravascular coagulation. Few hypercoagulable families are identified with CD141 gene mutations. Mice lacking functional CD141 die in-utero but not from thrombosis or bleeding but may indicate a vital role in embryogenesis.
|MOLECULAR INTERACTIONS -|
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD141
CD141 is regulated in vitro upregulation by cAMP, heat shock, and downregulated by TNF-a .
SUBSTRATES: No information.
ENZYMES WHICH MODIFY CD141: No information.
The role of the lectin-like domain is unresolved but possibly it is involved in adhesion. CD141 does not appear to actively internalized from the cell surface. Cell surface CD141 may be variably regulated by internalization in different tissues.
Database accession numbers
Revised June 25, 2008