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{{Infobox_gene}}
{{PBB_Controls
'''Thrombomodulin''' ('''TM'''), [[Cluster of differentiation|CD]]141 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.<ref>[http://www.ebi.ac.uk/interpro/IEntry?ac=IPR001491 IPR001491 Thrombomodulin] Accessed January 19, 2012.</ref> Thrombomodulin is also expressed on human [[mesothelial cell]],<ref>{{cite journal | vauthors = Verhagen HJ, Heijnen-Snyder GJ, Pronk A, Vroom TM, van Vroonhoven TJ, Eikelboom BC, Sixma JJ, de Groot PG | title = Thrombomodulin activity on mesothelial cells: perspectives for mesothelial cells as an alternative for endothelial cells for cell seeding on vascular grafts | journal = British Journal of Haematology | volume = 95 | issue = 3 | pages = 542–9 | date = Dec 1996 | pmid = 8943899 | doi=10.1046/j.1365-2141.1996.d01-1935.x}}</ref> [[monocyte]] and a [[dendritic cell]] subset.
| update_page = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
{{GNF_Protein_box
| image = PBB_Protein_THBD_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1adx.
| Name = Thrombomodulin
| HGNCid = 11784
| Symbol = THBD
| AltSymbols =; TM; CD141; THRM
| OMIM = 188040
| ECnumber = 
| Homologene = 308
| MGIid = 98736
| GeneAtlas_image1 = PBB_GE_THBD_203887_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_THBD_203888_at_tn.png
| Function = {{GNF_GO|id=GO:0004888 |text = transmembrane receptor activity}} {{GNF_GO|id=GO:0005509 |text = calcium ion binding}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0005529 |text = sugar binding}}
  | Component = {{GNF_GO|id=GO:0005887 |text = integral to plasma membrane}} {{GNF_GO|id=GO:0016020 |text = membrane}}
| Process = {{GNF_GO|id=GO:0007565 |text = female pregnancy}} {{GNF_GO|id=GO:0007596 |text = blood coagulation}} {{GNF_GO|id=GO:0009790 |text = embryonic development}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 7056
    | Hs_Ensembl = ENSG00000178726
    | Hs_RefseqProtein = NP_000352
    | Hs_RefseqmRNA = NM_000361
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 20
    | Hs_GenLoc_start = 22974270
    | Hs_GenLoc_end = 22978287
    | Hs_Uniprot = P07204
    | Mm_EntrezGene = 21824
    | Mm_Ensembl = ENSMUSG00000074743
    | Mm_RefseqmRNA = NM_009378
    | Mm_RefseqProtein = NP_033404
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 2
    | Mm_GenLoc_start = 148097654
    | Mm_GenLoc_end = 148099387
    | Mm_Uniprot = Q543W3
  }}
}}
{{SI}}
{{CMG}}


== Genetics and structure ==


In humans, thrombomodulin is encoded by the '''THBD''' [[gene]].<ref name="pmid2822087">{{cite journal | vauthors = Wen DZ, Dittman WA, Ye RD, Deaven LL, Majerus PW, Sadler JE | title = Human thrombomodulin: complete cDNA sequence and chromosome localization of the gene | journal = Biochemistry | volume = 26 | issue = 14 | pages = 4350–7  | date = Jul 1987 | pmid = 2822087 | doi = 10.1021/bi00388a025 }}</ref> The protein has a molecular mass of 74k[[Dalton (unit)|Da]], and consists of a single chain with six tandemly repeated [[EGF-like domain]]s, a [[Serine]]/[[Threonine]]-rich spacer and a [[transmembrane]] domain.<ref>{{cite journal|authorlink1=J. Evan Sadler | vauthors = Sadler JE | title = Thrombomodulin structure and function | journal = Thrombosis and Haemostasis| volume = 78 | issue = 1 | pages = 392–5  | date = Jul 1997 | pmid = 9198185}}</ref>


'''Thrombomodulin''', [[Cluster of differentiation|CD]]141 or BDCA-3 is an [[integral membrane protein]] expressed on the surface of endothelial cells.
== Function ==


The protein has a molecular mass of 74k[[Dalton_(unit)|Da]], and consists of a single chain with 5 distinct domains.
Thrombomodulin functions as a [[Cofactor (biochemistry)|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 [[Carboxypeptidase B2|thrombin-activatable fibrinolysis inhibitor]] (TAFI, aka carboxypeptidase B2) into its active form.{{citation needed|date=February 2015}}


It functions as a cofactor in the [[thrombin]]-induced activation of [[protein C]] in the [[anticoagulant]] pathway by forming a 1:1 stochiometric complex with thrombin. This raises the speed of protein C activation thousandfold. Thrombomodulin-bound thrombin has no procoagulant effect. The TT-complex also stimulates fibrinolysis by cleaving [[thrombin-activatable fibrinolysis inhibitor]] (TAFI) into its active form.
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).{{citation needed|date=February 2015}}


The [[antigen]] described as BDCA-3<ref>Dzionek, Andrzej; Fuchs,Anja; Schmidt, Petra; Cremer, Sabine; Zysk, Monika; Miltenyi, Stefan; Buck, David W. & Schmitz, Jürgen (2000): BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood. ''Journal of Immuology'' '''165'''(11): 6037-6046. [http://www.jimmunol.org/cgi/reprint/165/11/6037.pdf PDF fulltext]</ref> has turned out to be identical to thrombomodulin.<ref>Dzionek, Andrzej; Inagaki, Yoshimasa; Okawa, Katsuya; Nagafune, Jun; Röck, Jürgen; Sohma, Yoshiaki; Winkels, Gregor; Zysk, Monika; Yamaguchi, Yasunori & Schmitz, Jürgen (2002): Plasmacytoid dendritic cells: from specific surface markers to specific cellular functions, ''Human Immunology'' '''63'''(12): 1133-1148. {{DOI|10.1016/S0198-8859(02)00752-8}} (HTML abstract)</ref> Thus, it was revealed that this molecule also occurs on a very rare (0.02%) subset of human [[dendritic cell]]s called MDC2. Its function on these cells is unknown at present, but apparently, thrombomodulin has at least one other [[ligand (biochemistry)|ligand]] apart from thrombin, because anticoaglulation is a commonplace function, in contrast to the rarity of MDC2 cells.
The [[antigen]] described as BDCA-3<ref name="pmid11086035">{{cite journal | vauthors = Dzionek A, Fuchs A, Schmidt P, Cremer S, Zysk M, Miltenyi S, Buck DW, Schmitz J | title = BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood | journal = Journal of Immunology | volume = 165 | issue = 11 | pages = 6037–46  | date = Dec 2000 | pmid = 11086035 | doi = 10.4049/jimmunol.165.11.6037 }}</ref> has turned out to be identical to thrombomodulin.<ref name="pmid12480257">{{cite journal | vauthors = Dzionek A, Inagaki Y, Okawa K, Nagafune J, Röck J, Sohma Y, Winkels G, Zysk M, Yamaguchi Y, Schmitz J | title = Plasmacytoid dendritic cells: from specific surface markers to specific cellular functions | journal = Human Immunology | volume = 63 | issue = 12 | pages = 1133–48  | date = Dec 2002 | pmid = 12480257 | doi = 10.1016/S0198-8859(02)00752-8 }}</ref> Thus, it was revealed that this molecule also occurs on a very rare (0.02%) subset of human [[dendritic cell]]s called MDC2. Its function on these cells is unknown.{{citation needed|date=February 2015}}


==References==
== Interactions ==
<references/>


==Further reading==
Thrombomodulin has been shown to [[Protein-protein interaction|interact]] with [[thrombin]].<ref name=pmid8663147>{{cite journal | vauthors = Bajzar L, Morser J, Nesheim M | title = TAFI, or plasma procarboxypeptidase B, couples the coagulation and fibrinolytic cascades through the thrombin-thrombomodulin complex | journal = The Journal of Biological Chemistry | volume = 271 | issue = 28 | pages = 16603–8  | date = Jul 1996 | pmid = 8663147 | doi = 10.1074/jbc.271.28.16603 }}</ref><ref name=pmid2544585>{{cite journal | vauthors = Jakubowski HV, Owen WG | title = Macromolecular specificity determinants on thrombin for fibrinogen and thrombomodulin | journal = The Journal of Biological Chemistry | volume = 264 | issue = 19 | pages = 11117–21  | date = Jul 1989 | pmid = 2544585 }}</ref>
 
== References ==
{{Reflist}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Esmon CT | title = Thrombomodulin as a model of molecular mechanisms that modulate protease specificity and function at the vessel surface | journal = FASEB Journal | volume = 9 | issue = 10 | pages = 946–55  | date = Jul 1995 | pmid = 7615164 }}
| citations =
* {{cite journal | vauthors = Ohlin AK, Norlund L, Marlar RA | title = Thrombomodulin gene variations and thromboembolic disease | journal = Thrombosis and Haemostasis | volume = 78 | issue = 1 | pages = 396–400  | date = Jul 1997 | pmid = 9198186 }}
*{{cite journal | author=Esmon CT |title=Thrombomodulin as a model of molecular mechanisms that modulate protease specificity and function at the vessel surface. |journal=FASEB J. |volume=9 |issue= 10 |pages= 946-55 |year= 1995 |pmid= 7615164 |doi=  }}
* {{cite journal | vauthors = Van de Wouwer M, Collen D, Conway EM | title = Thrombomodulin-protein C-EPCR system: integrated to regulate coagulation and inflammation | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 24 | issue = 8 | pages = 1374–83  | date = Aug 2004 | pmid = 15178554 | doi = 10.1161/01.ATV.0000134298.25489.92 }}
*{{cite journal | author=Ohlin AK, Norlund L, Marlar RA |title=Thrombomodulin gene variations and thromboembolic disease. |journal=Thromb. Haemost. |volume=78 |issue= 1 |pages= 396-400 |year= 1997 |pmid= 9198186 |doi=  }}
* {{cite journal | vauthors = Boffa MC, Jackman RW, Peyri N, Boffa JF, George B | title = Thrombomodulin in the central nervous system | journal = Nouvelle Revue Française D'hématologie | volume = 33 | issue = 6 | pages = 423–9 | year = 1991 | pmid = 1667949 }}
*{{cite journal | author=Van de Wouwer M, Collen D, Conway EM |title=Thrombomodulin-protein C-EPCR system: integrated to regulate coagulation and inflammation. |journal=Arterioscler. Thromb. Vasc. Biol. |volume=24 |issue= 8 |pages= 1374-83 |year= 2005 |pmid= 15178554 |doi= 10.1161/01.ATV.0000134298.25489.92 }}
* {{cite journal | vauthors = Jackman RW, Beeler DL, Fritze L, Soff G, Rosenberg RD | title = Human thrombomodulin gene is intron depleted: nucleic acid sequences of the cDNA and gene predict protein structure and suggest sites of regulatory control | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 84 | issue = 18 | pages = 6425–9 | year = 1987 | pmid = 2819876 | pmc = 299089 | doi = 10.1073/pnas.84.18.6425 | bibcode =  1987PNAS...84.6425J}}
*{{cite journal | author=Boffa MC, Jackman RW, Peyri N, ''et al.'' |title=Thrombomodulin in the central nervous system. |journal=Nouvelle revue française d'hématologie |volume=33 |issue= 6 |pages= 423-9 |year= 1992 |pmid= 1667949 |doi=  }}
* {{cite journal | vauthors = Suzuki K, Kusumoto H, Deyashiki Y, Nishioka J, Maruyama I, Zushi M, Kawahara S, Honda G, Yamamoto S, Horiguchi S | title = Structure and expression of human thrombomodulin, a thrombin receptor on endothelium acting as a cofactor for protein C activation | journal = The EMBO Journal | volume = 6 | issue = 7 | pages = 1891–7  | date = Jul 1987 | pmid = 2820710 | pmc = 553573 }}
*{{cite journal | author=Jakubowski HV, Owen WG |title=Macromolecular specificity determinants on thrombin for fibrinogen and thrombomodulin. |journal=J. Biol. Chem. |volume=264 |issue= 19 |pages= 11117-21 |year= 1989 |pmid= 2544585 |doi=  }}
* {{cite journal | vauthors = Wen DZ, Dittman WA, Ye RD, Deaven LL, Majerus PW, Sadler JE | title = Human thrombomodulin: complete cDNA sequence and chromosome localization of the gene | journal = Biochemistry | volume = 26 | issue = 14 | pages = 4350–7  | date = Jul 1987 | pmid = 2822087 | doi = 10.1021/bi00388a025 }}
*{{cite journal  | author=Jackman RW, Beeler DL, Fritze L, ''et al.'' |title=Human thrombomodulin gene is intron depleted: nucleic acid sequences of the cDNA and gene predict protein structure and suggest sites of regulatory control. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=84 |issue= 18 |pages= 6425-9 |year= 1987 |pmid= 2819876 |doi= }}
* {{cite journal | vauthors = Shirai T, Shiojiri S, Ito H, Yamamoto S, Kusumoto H, Deyashiki Y, Maruyama I, Suzuki K | title = Gene structure of human thrombomodulin, a cofactor for thrombin-catalyzed activation of protein C | journal = Journal of Biochemistry | volume = 103 | issue = 2 | pages = 281–5  | date = Feb 1988 | pmid = 2836377 }}
*{{cite journal | author=Suzuki K, Kusumoto H, Deyashiki Y, ''et al.'' |title=Structure and expression of human thrombomodulin, a thrombin receptor on endothelium acting as a cofactor for protein C activation. |journal=EMBO J. |volume=6 |issue= 7 |pages= 1891-7 |year= 1987 |pmid= 2820710 |doi= }}
* {{cite journal | vauthors = Yonezawa S, Maruyama I, Tanaka S, Nakamura T, Sato E | title = Immunohistochemical localization of thrombomodulin in chorionic diseases of the uterus and choriocarcinoma of the stomach. A comparative study with the distribution of human chorionic gonadotropin | journal = Cancer | volume = 62 | issue = 3 | pages = 569–76  | date = Aug 1988 | pmid = 2839283 | doi = 10.1002/1097-0142(19880801)62:3<569::AID-CNCR2820620322>3.0.CO;2-T }}
*{{cite journal | author=Wen DZ, Dittman WA, Ye RD, ''et al.'' |title=Human thrombomodulin: complete cDNA sequence and chromosome localization of the gene. |journal=Biochemistry |volume=26 |issue= 14 |pages= 4350-7 |year= 1987 |pmid= 2822087 |doi= }}
* {{cite journal | vauthors = Ishii H, Majerus PW | title = Thrombomodulin is present in human plasma and urine | journal = The Journal of Clinical Investigation | volume = 76 | issue = 6 | pages = 2178–81  | date = Dec 1985 | pmid = 3001144 | doi = 10.1172/JCI112225 | pmc=424339}}
*{{cite journal | author=Shirai T, Shiojiri S, Ito H, ''et al.'' |title=Gene structure of human thrombomodulin, a cofactor for thrombin-catalyzed activation of protein C. |journal=J. Biochem. |volume=103 |issue= 2 |pages= 281-5 |year= 1988 |pmid= 2836377 |doi=  }}
* {{cite journal | vauthors = Adler M, Seto MH, Nitecki DE, Lin JH, Light DR, Morser J | title = The structure of a 19-residue fragment from the C-loop of the fourth epidermal growth factor-like domain of thrombomodulin | journal = The Journal of Biological Chemistry | volume = 270 | issue = 40 | pages = 23366–72  | date = Oct 1995 | pmid = 7559494 | doi = 10.1074/jbc.270.40.23366 }}
*{{cite journal | author=Yonezawa S, Maruyama I, Tanaka S, ''et al.'' |title=Immunohistochemical localization of thrombomodulin in chorionic diseases of the uterus and choriocarcinoma of the stomach. A comparative study with the distribution of human chorionic gonadotropin. |journal=Cancer |volume=62 |issue= 3 |pages= 569-76 |year= 1988 |pmid= 2839283 |doi= }}
* {{cite journal | vauthors = Ohlin AK, Marlar RA | title = The first mutation identified in the thrombomodulin gene in a 45-year-old man presenting with thromboembolic disease | journal = Blood | volume = 85 | issue = 2 | pages = 330–6  | date = Jan 1995 | pmid = 7811989 }}
*{{cite journal | author=Ishii H, Majerus PW |title=Thrombomodulin is present in human plasma and urine. |journal=J. Clin. Invest. |volume=76 |issue= 6 |pages= 2178-81 |year= 1986 |pmid= 3001144 |doi= }}
* {{cite journal | vauthors = Srinivasan J, Hu S, Hrabal R, Zhu Y, Komives EA, Ni F | title = Thrombin-bound structure of an EGF subdomain from human thrombomodulin determined by transferred nuclear Overhauser effects | journal = Biochemistry | volume = 33 | issue = 46 | pages = 13553–60  | date = Nov 1994 | pmid = 7947766 | doi = 10.1021/bi00250a007 }}
*{{cite journal | author=Adler M, Seto MH, Nitecki DE, ''et al.'' |title=The structure of a 19-residue fragment from the C-loop of the fourth epidermal growth factor-like domain of thrombomodulin. |journal=J. Biol. Chem. |volume=270 |issue= 40 |pages= 23366-72 |year= 1995 |pmid= 7559494 |doi= }}
* {{cite journal | vauthors = Gerlitz B, Hassell T, Vlahos CJ, Parkinson JF, Bang NU, Grinnell BW | title = Identification of the predominant glycosaminoglycan-attachment site in soluble recombinant human thrombomodulin: potential regulation of functionality by glycosyltransferase competition for serine474 | journal = The Biochemical Journal | volume = 295 | issue = 1 | pages = 131–40  | date = Oct 1993 | pmid = 8216207 | pmc = 1134829 | doi=10.1042/bj2950131}}
*{{cite journal | author=Ohlin AK, Marlar RA |title=The first mutation identified in the thrombomodulin gene in a 45-year-old man presenting with thromboembolic disease. |journal=Blood |volume=85 |issue= 2 |pages= 330-6 |year= 1995 |pmid= 7811989 |doi=  }}
* {{cite journal | vauthors = Yasuda K, Espinosa R, Davis EM, Le Beau MM, Bell GI | title = Human somatostatin receptor genes: localization of SSTR5 to human chromosome 20p11.2 | journal = Genomics | volume = 17 | issue = 3 | pages = 785–6  | date = Sep 1993 | pmid = 8244401 | doi = 10.1006/geno.1993.1410 }}
*{{cite journal | author=Srinivasan J, Hu S, Hrabal R, ''et al.'' |title=Thrombin-bound structure of an EGF subdomain from human thrombomodulin determined by transferred nuclear Overhauser effects. |journal=Biochemistry |volume=33 |issue= 46 |pages= 13553-60 |year= 1994 |pmid= 7947766 |doi= }}
* {{cite journal | vauthors = Yamamoto S, Mizoguchi T, Tamaki T, Ohkuchi M, Kimura S, Aoki N | title = Urinary thrombomodulin, its isolation and characterization | journal = Journal of Biochemistry | volume = 113 | issue = 4 | pages = 433–40  | date = Apr 1993 | pmid = 8390446 |url=http://joi.jlc.jst.go.jp/JST.Journalarchive/biochemistry1922/113.433?lang=en&from=PubMed}}
*{{cite journal | author=Gerlitz B, Hassell T, Vlahos CJ, ''et al.'' |title=Identification of the predominant glycosaminoglycan-attachment site in soluble recombinant human thrombomodulin: potential regulation of functionality by glycosyltransferase competition for serine474. |journal=Biochem. J. |volume=295 ( Pt 1) |issue= |pages= 131-40 |year= 1993 |pmid= 8216207 |doi= }}
* {{cite journal | vauthors = Meininger DP, Hunter MJ, Komives EA | title = Synthesis, activity, and preliminary structure of the fourth EGF-like domain of thrombomodulin | journal = Protein Science | volume = 4 | issue = 9 | pages = 1683–95  | date = Sep 1995 | pmid = 8528067 | doi = 10.1002/pro.5560040904 | pmc=2143218}}
*{{cite journal | author=Yasuda K, Espinosa R, Davis EM, ''et al.'' |title=Human somatostatin receptor genes: localization of SSTR5 to human chromosome 20p11.2. |journal=Genomics |volume=17 |issue= 3 |pages= 785-6 |year= 1993 |pmid= 8244401 |doi= 10.1006/geno.1993.1410 }}
* {{cite journal | vauthors = Maglott DR, Feldblyum TV, Durkin AS, Nierman WC | title = Radiation hybrid mapping of SNAP, PCSK2, and THBD (human chromosome 20p) | journal = Mammalian Genome | volume = 7 | issue = 5 | pages = 400–1  | date = May 1996 | pmid = 8661740 | doi = 10.1007/s003359900120 }}
*{{cite journal | author=Yamamoto S, Mizoguchi T, Tamaki T, ''et al.'' |title=Urinary thrombomodulin, its isolation and characterization. |journal=J. Biochem. |volume=113 |issue= 4 |pages= 433-40 |year= 1993 |pmid= 8390446 |doi= }}
*{{cite journal | author=Meininger DP, Hunter MJ, Komives EA |title=Synthesis, activity, and preliminary structure of the fourth EGF-like domain of thrombomodulin. |journal=Protein Sci. |volume=4 |issue= 9 |pages= 1683-95 |year= 1996 |pmid= 8528067 |doi= }}
*{{cite journal | author=Maglott DR, Feldblyum TV, Durkin AS, Nierman WC |title=Radiation hybrid mapping of SNAP, PCSK2, and THBD (human chromosome 20p). |journal=Mamm. Genome |volume=7 |issue= 5 |pages= 400-1 |year= 1996 |pmid= 8661740 |doi= }}
}}
{{refend}}
{{refend}}


== External links ==
* [https://www.ncbi.nlm.nih.gov/books/NBK1367/  GeneReviews/NCBI/NIH/UW entry on Atypical Hemolytic-Uremic Syndrome]
* [https://www.ncbi.nlm.nih.gov/omim/277400,120700,120920,134370,134371,138470,188040,217030,235400,605336,605337,612922,612923,612924,612925,612926,120700,120920,134370,134371,138470,188040,217030,235400,605336,605337,612922,612923,612924,612925,612926  OMIM entries on Atypical Hemolytic-Uremic Syndrome]
{{PDB Gallery|geneid=7056}}
{{Clusters of differentiation}}
{{Clusters of differentiation}}


[[Category:Coagulation system]]
[[Category:Coagulation system]]
[[Category:Clusters of differentiation]]
[[Category:Clusters of differentiation]]
[[de:Thrombomodulin]]
[[pl:Trombomodulina]]
[[ru:Тромбомодулин]]
{{WH}}
{{WikiDoc Sources}}

Latest revision as of 07:10, 10 January 2019

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
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Ensembl

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UniProt

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RefSeq (mRNA)

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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.[1] Thrombomodulin is also expressed on human mesothelial cell,[2] monocyte and a dendritic cell subset.

Genetics and structure

In humans, thrombomodulin is encoded by the THBD gene.[3] 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.[4]

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).[citation needed]

The antigen described as BDCA-3[5] has turned out to be identical to thrombomodulin.[6] 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.[7][8]

References

  1. ↑ IPR001491 Thrombomodulin Accessed January 19, 2012.
  2. ↑ Verhagen HJ, Heijnen-Snyder GJ, Pronk A, Vroom TM, van Vroonhoven TJ, Eikelboom BC, Sixma JJ, de Groot PG (Dec 1996). "Thrombomodulin activity on mesothelial cells: perspectives for mesothelial cells as an alternative for endothelial cells for cell seeding on vascular grafts". British Journal of Haematology. 95 (3): 542–9. doi:10.1046/j.1365-2141.1996.d01-1935.x. PMID 8943899.
  3. ↑ Wen DZ, Dittman WA, Ye RD, Deaven LL, Majerus PW, Sadler JE (Jul 1987). "Human thrombomodulin: complete cDNA sequence and chromosome localization of the gene". Biochemistry. 26 (14): 4350–7. doi:10.1021/bi00388a025. PMID 2822087.
  4. ↑ Sadler JE (Jul 1997). "Thrombomodulin structure and function". Thrombosis and Haemostasis. 78 (1): 392–5. PMID 9198185.
  5. ↑ Dzionek A, Fuchs A, Schmidt P, Cremer S, Zysk M, Miltenyi S, Buck DW, Schmitz J (Dec 2000). "BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood". Journal of Immunology. 165 (11): 6037–46. doi:10.4049/jimmunol.165.11.6037. PMID 11086035.
  6. ↑ Dzionek A, Inagaki Y, Okawa K, Nagafune J, Röck J, Sohma Y, Winkels G, Zysk M, Yamaguchi Y, Schmitz J (Dec 2002). "Plasmacytoid dendritic cells: from specific surface markers to specific cellular functions". Human Immunology. 63 (12): 1133–48. doi:10.1016/S0198-8859(02)00752-8. PMID 12480257.
  7. ↑ Bajzar L, Morser J, Nesheim M (Jul 1996). "TAFI, or plasma procarboxypeptidase B, couples the coagulation and fibrinolytic cascades through the thrombin-thrombomodulin complex". The Journal of Biological Chemistry. 271 (28): 16603–8. doi:10.1074/jbc.271.28.16603. PMID 8663147.
  8. ↑ Jakubowski HV, Owen WG (Jul 1989). "Macromolecular specificity determinants on thrombin for fibrinogen and thrombomodulin". The Journal of Biological Chemistry. 264 (19): 11117–21. PMID 2544585.

Further reading

External links

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