Thrombomodulin (TM)

CD141; THBD; BDCA3; THRM; Fetomodulin

SPN	W281
HGNC	11784
MGI	98736
PubMed	12871287
RGD	621299
UniProt	P07204
Wiki	Thrombomodulin

Thrombomodulin (TM) is the cell surface receptor for thrombin. When occupied, thrombomodulin converts thrombin from a procoagulant protein into the activator of Protein C. Once activated Protein C (APC) has been generated, thrombomodulin acts as a major anticoagulant through its ability to inactivate various blood factors (Va, VΙΙΙa, Xa and XΙΙΙa). In competing for thrombin binding, thrombomodulin inhibits the proteolytic effect of thrombin in its clotting of fibrinogen, the inactivation of Protein S and the induction of platelet aggregation.

TM is an integral membrane glycoprotein resembling in structure the low-density lipoprotein (LDL) receptor.TM possesses several EGF repeats, of which numbers five and six are responsible for the high affinity binding of thrombin (Kd = 0.5 nM).

Reference

"Structure and expression of human thrombomodulin, a thrombin receptor on endothelium acting as a cofactor for protein C activation."
EMBO J. 6:1891-1897(1987) [PubMed] [Europe PMC] [Abstract]

"Human thrombomodulin: complete cDNA sequence and chromosome localization of the gene."
Biochemistry 26:4350-4357(1987) [PubMed] [Europe PMC] [Abstract]

"Human thrombomodulin gene is intron depleted: nucleic acid sequences of the cDNA and gene predict protein structure and suggest sites of regulatory control."
Proc. Natl. Acad. Sci. U.S.A. 84:6425-6429(1987) [PubMed] [Europe PMC] [Abstract]

"Gene structure of human thrombomodulin, a cofactor for thrombin-catalyzed activation of protein C."
J. Biochem. 103:281-285(1988) [PubMed] [Europe PMC] [Abstract]

"The DNA sequence and comparative analysis of human chromosome 20."
Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Identification of the predominant glycosaminoglycan-attachment site in soluble recombinant human thrombomodulin: potential regulation of functionality by glycosyltransferase competition for serine 474."
Biochem. J. 295:131-140(1993) [PubMed] [Europe PMC] [Abstract]

"Urinary thrombomodulin, its isolation and characterization."
J. Biochem. 113:433-440(1993) [PubMed] [Europe PMC] [Abstract]

"The structure of a 19-residue fragment from the C-loop of the fourth epidermal growth factor-like domain of thrombomodulin."
J. Biol. Chem. 270:23366-23372(1995) [PubMed] [Europe PMC] [Abstract]

"Synthesis, activity, and preliminary structure of the fourth EGF-like domain of thrombomodulin."
Protein Sci. 4:1683-1695(1995) [PubMed] [Europe PMC] [Abstract]

"Thrombin-bound structure of an EGF subdomain from human thrombomodulin determined by transferred nuclear Overhauser effects."
Biochemistry 33:13553-13560(1994) [PubMed] [Europe PMC] [Abstract]

"Structural resiliency of an EGF-like subdomain bound to its target protein, thrombin."
Protein Sci. 5:195-203(1996) [PubMed] [Europe PMC] [Abstract]

"Structure of the fifth EGF-like domain of thrombomodulin: an EGF-like domain with a novel disulfide-bonding pattern."
J. Mol. Biol. 273:913-926(1997) [PubMed] [Europe PMC] [Abstract]

"The first mutation identified in the thrombomodulin gene in a 45-year-old man presenting with thromboembolic disease."
Blood 85:330-336(1995) [PubMed] [Europe PMC] [Abstract]

"Thrombomodulin gene variations and thromboembolic disease."
Thromb. Haemost. 78:396-400(1997) [PubMed] [Europe PMC] [Abstract]

"A common thrombomodulin amino acid dimorphism is associated with myocardial infarction."
Thromb. Haemost. 77:248-251(1997) [PubMed] [Europe PMC] [Abstract]

"A mutation in the thrombomodulin gene, 127G to A coding for Ala25Thr, and the risk of myocardial infarction in men."
Thromb. Haemost. 80:743-748(1998) [PubMed] [Europe PMC] [Abstract]

"Thrombomodulin Ala455Val polymorphism and risk of coronary heart disease."
Circulation 103:1386-1389(2001) [PubMed] [Europe PMC] [Abstract]

"Mutations in the thrombomodulin gene are rare in patients with severe thrombophilia."
Br. J. Haematol. 118:595-599(2002) [PubMed] [Europe PMC] [Abstract]

"Thrombomodulin mutations in atypical hemolytic-uremic syndrome."
N. Engl. J. Med. 361:345-357(2009) [PubMed] [Europe PMC] [Abstract]

"Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome."
Hum. Mutat. 31:E1445-E1460(2010) [PubMed] [Europe PMC] [Abstract]