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thrombomodulin; TM; fetomodulin; CD141 (THBD, THRM)
Function:
- specific endothelial cell receptor
- forms a 1:1 stoichiometric complex with thrombin
- thrombin-thrombomodulin complex activates protein C
- activated protein C scissions the activated cofactors of the coagulation mechanism, factor Va & factor VIIIa, thus diminishes the amount of thrombin generated
- iron & 2-oxoglutarate dependent 3-hydroxylation of Asp & Asn is (R) stereospecific within EGF domains
Thrombomodulin stimulates:
1) thrombin-mediated activatation of protein C
2) antithrombin III inactivation of thrombin
Thrombomodulin inhibits:
1) thrombin-mediated proteolysis of fibrinogen
2) thrombin-mediated proteolysis of factor V
3) thrombin activation of platelets
Structure:
- N-glycosylated
- contains 1 C-type lectin domain
- contains 6 EGF-like domains
Compartment: membrane
Expression:
- uniquely expressed by endothelial cells
Pathology:
- defects in THBD are the cause of thrombophilia due to thrombomodulin defect
Interactions
molecular events
Specific
recombinant thrombomodulin
General
glycoprotein
plasma membrane protein
Properties
SIZE: entity length = 575 aa
MW = 60 kD
COMPARTMENT: cellular membrane
MOTIF: signal sequence {1-18}
C-type lectin {31-169}
MOTIF: N-glycosylation site {N47}
N-glycosylation site {N115}
N-glycosylation site {N116}
cysteine residue {C137}
MODIFICATION: cysteine residue {C158}
cysteine residue {C158}
MODIFICATION: cysteine residue {C137}
EGF domain {241-281}
MOTIF: cysteine residue {C245}
MODIFICATION: cysteine residue {C256}
cysteine residue {C252}
MODIFICATION: cysteine residue {C265}
cysteine residue {C256}
MODIFICATION: cysteine residue {C245}
cysteine residue {C265}
MODIFICATION: cysteine residue {C252}
cysteine residue {C267}
MODIFICATION: cysteine residue {C280}
cysteine residue {C280}
MODIFICATION: cysteine residue {C267}
EGF domain {284-324}
MOTIF: cysteine residue {C288}
MODIFICATION: cysteine residue {C296}
cysteine residue {C292}
MODIFICATION: cysteine residue {C308}
cysteine residue {C296}
MODIFICATION: cysteine residue {C288}
cysteine residue {C308}
MODIFICATION: cysteine residue {C292}
cysteine residue {C310}
MODIFICATION: cysteine residue {C323}
cysteine residue {C323}
MODIFICATION: cysteine residue {C310}
EGF domain {325-363}
MOTIF: cysteine residue {C329}
MODIFICATION: cysteine residue {C340}
cysteine residue {C336}
MODIFICATION: cysteine residue {C349}
cysteine residue {C340}
MODIFICATION: cysteine residue {C329}
cysteine residue {C349}
MODIFICATION: cysteine residue {C336}
cysteine residue {C351}
MODIFICATION: cysteine residue {C362}
cysteine residue {C362}
MODIFICATION: cysteine residue {C351}
EGF domain {365-405}
MOTIF: cysteine residue {C369}
MODIFICATION: cysteine residue {C378}
cysteine residue {C374}
MODIFICATION: cysteine residue {C388}
cysteine residue {C378}
MODIFICATION: cysteine residue {C369}
N-glycosylation site {N382}
cysteine residue {C388}
MODIFICATION: cysteine residue {C374}
cysteine residue {C390}
MODIFICATION: cysteine residue {C404}
EGF domain {404-440}
MOTIF: cysteine residue {C404}
MODIFICATION: cysteine residue {C390}
cysteine residue {C408}
MODIFICATION: cysteine residue {C413}
N-glycosylation site {N409}
cysteine residue {C413}
MODIFICATION: cysteine residue {C408}
cysteine residue {C417}
MODIFICATION: cysteine residue {C425}
cysteine residue {C425}
MODIFICATION: cysteine residue {C417}
cysteine residue {C427}
MODIFICATION: cysteine residue {C439}
cysteine residue {C439}
MODIFICATION: cysteine residue {C427}
EGF domain {441-481}
MOTIF: cysteine residue {C445}
MODIFICATION: cysteine residue {C455}
cysteine residue {C451}
MODIFICATION: cysteine residue {C464}
cysteine residue {C455}
MODIFICATION: cysteine residue {C445}
cysteine residue {C464}
MODIFICATION: cysteine residue {C451}
cysteine residue {C466}
MODIFICATION: cysteine residue {C480}
cysteine residue {C480}
MODIFICATION: cysteine residue {C466}
Ser glycosylation site {S490}
Ser glycosylation site {S492}
transmembrane domain {516-539}
Database Correlations
OMIM 188040
MORBIDMAP 188040
UniProt P07204
PFAM correlations
Entrez Gene 7056
Kegg hsa:7056
References
- Textbook of Biochemistry with Clinical Correlations,
3rd ed., TM Devlin (ed), Wiley-Liss, NY 1992 pg 973
- Walker FJ, Fay PJ.
Regulation of blood coagulation by the protein C system.
FASEB J. 1992 May;6(8):2561-7. Review.
PMID: 1317308
Component-of
molecular complex