CD141 THBD(Thrombomodulin), TM, fetomodulin
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Endothelial Cell
Keratinocyte
Platelet
Megakaryocyte
Monocyte
Neutrophil
Syncytiotrophoblast
Synovial Cell
Myeloid Cell
Muscle, Smooth
Blood vessel
75 / 75
105 / 105

Expression
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.



Structure
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. 
 
MOLECULAR MASS
Cell Type Unreduced Reduced Comment
Endothelial cells 75 kDa 105 kDa

POST-TRANSCRIPTIONAL MODIFICATION

CD141 gene has no introns.

POST-TRANSLATIONAL MODIFICATION

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
LIGANDS AND MOLECULES ASSOCIATED WITH CD141
Molecule Comment
Thrombin Undergoes a conformational change in the reactive center, resulting in the loss of anti-coagulant procoagulant function of thrombin
Protein C Activated by CD141-bound thrombin
Plasma pro-carboxypeptidase B (or TAFI = thrombin activatable fibrinolysis inhibitor) Activated by CD141-bound thrombin



Function
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.

BIOCHEMICAL ACTIVITY

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.

Comments
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
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 7056P07204
Antibodies
1A4   View Reactivity
QBEND/40   View Reactivity

Revised June 25, 2008


Contact us: Webmaster |  509-335-9515 | Accessibility | Copyright | Policies
College of Veterinary Medicine Washington State University, Pullman, WA, 99164-7010 USA
Copyright 1995-2003 Washington State University