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Thrombomodulin

NameThrombomodulin
Synonyms
  • Fetomodulin
  • THRM
  • TM
Gene NameTHBD
OrganismHuman
Amino acid sequence
>lcl|BSEQ0016328|Thrombomodulin
MLGVLVLGALALAGLGFPAPAEPQPGGSQCVEHDCFALYPGPATFLNASQICDGLRGHLM
TVRSSVAADVISLLLNGDGGVGRRRLWIGLQLPPGCGDPKRLGPLRGFQWVTGDNNTSYS
RWARLDLNGAPLCGPLCVAVSAAEATVPSEPIWEEQQCEVKADGFLCEFHFPATCRPLAV
EPGAAAAAVSITYGTPFAARGADFQALPVGSSAAVAPLGLQLMCTAPPGAVQGHWAREAP
GAWDCSVENGGCEHACNAIPGAPRCQCPAGAALQADGRSCTASATQSCNDLCEHFCVPNP
DQPGSYSCMCETGYRLAADQHRCEDVDDCILEPSPCPQRCVNTQGGFECHCYPNYDLVDG
ECVEPVDPCFRANCEYQCQPLNQTSYLCVCAEGFAPIPHEPHRCQMFCNQTACPADCDPN
TQASCECPEGYILDDGFICTDIDECENGGFCSGVCHNLPGTFECICGPDSALARHIGTDC
DSGKVDGGDSGSGEPPPSPTPGSTLTPPAVGLVHSGLLIGISIASLCLVVALLALLCHLR
KKQGAARAKMEYKCAAPSKEVVLQHVRTERTPQRL
Number of residues575
Molecular Weight60328.72
Theoretical pI4.54
GO Classification
Functions
  • transmembrane signaling receptor activity
  • receptor activity
  • calcium ion binding
Processes
  • leukocyte migration
  • response to cAMP
  • negative regulation of fibrinolysis
  • negative regulation of platelet activation
  • response to lipopolysaccharide
  • female pregnancy
  • negative regulation of blood coagulation
  • response to X-ray
  • blood coagulation
Components
  • plasma membrane
  • extracellular space
  • cell surface
  • integral component of plasma membrane
General FunctionTransmembrane signaling receptor activity
Specific FunctionThrombomodulin is a specific endothelial cell receptor that forms a 1:1 stoichiometric complex with thrombin. This complex is responsible for the conversion of protein C to the activated protein C (protein Ca). Once evolved, protein Ca scissions the activated cofactors of the coagulation mechanism, factor Va and factor VIIIa, and thereby reduces the amount of thrombin generated.
Pfam Domain Function
Transmembrane Regions516-539
GenBank Protein ID736251
UniProtKB IDP07204
UniProtKB Entry NameTRBM_HUMAN
Cellular LocationMembrane
Gene sequence
>lcl|BSEQ0016329|Thrombomodulin (THBD)
ATGCTTGGGGTCCTGGTCCTTGGCGCGCTGGCCCTGGCCGGCCTGGGGTTCCCCGCACCC
GCAGAGCCGCAGCCGGGTGGCAGCCAGTGCGTCGAGCACGACTGCTTCGCGCTCTACCCG
GGCCCCGCGACCTTCCTCAATGCCAGTCAGATCTGCGACGGACTGCGGGGCCACCTAATG
ACAGTGCGCTCCTCGGTGGCTGCCGATGTCATTTCCTTGCTACTGAACGGCGACGGCGGC
GTTGGCCGCCGGCGCCTCTGGATCGGCCTGCAGCTGCCACCCGGCTGCGGCGACCCCAAG
CGCCTCGGGCCCCTGCGCGGCTTCCAGTGGGTTACGGGAGACAACAACACCAGCTATAGC
AGGTGGGCACGGCTCGACCTCAATGGGGCTCCCCTCTGCGGCCCGTTGTGCGTCGCTGTC
TCCGCTGCTGAGGCCACTGTGCCCAGCGAGCCGATCTGGGAGGAGCAGCAGTGCGAAGTG
AAGGCCGATGGCTTCCTCTGCGAGTTCCACTTCCCAGCCACCTGCAGGCCACTGGCTGTG
GAGCCCGGCGCCGCGGCTGCCGCCGTCTCGATCACCTACGGCACCCCGTTCGCGGCCCGC
GGAGCGGACTTCCAGGCGCTGCCGGTGGGCAGCTCCGCCGCGGTGGCTCCCCTCGGCTTA
CAGCTAATGTGCACCGCGCCGCCCGGAGCGGTCCAGGGGCACTGGGCCAGGGAGGCGCCG
GGCGCTTGGGACTGCAGCGTGGAGAACGGCGGCTGCGAGCACGCGTGCAATGCGATCCCT
GGGGCTCCCCGCTGCCAGTGCCCAGCCGGCGCCGCCCTGCAGGCAGACGGGCGCTCCTGC
ACCGCATCCGCGACGCAGTCCTGCAACGACCTCTGCGAGCACTTCTGCGTTCCCAACCCC
GACCAGCCGGGCTCCTACTCGTGCATGTGCGAGACCGGCTACCGGCTGGCGGCCGACCAA
CACCGGTGCGAGGACGTGGATGACTGCATACTGGAGCCCAGTCCGTGTCCGCAGCGCTGT
GTCAACACACAGGGTGGCTTCGAGTGCCACTGCTACCCTAACTACGACCTGGTGGACGGC
GAGTGTGTGGAGCCCGTGGACCCGTGCTTCAGAGCCAACTGCGAGTACCAGTGCCAGCCC
CTGAACCAAACTAGCTACCTCTGCGTCTGCGCCGAGGGCTTCGCGCCCATTCCCCACGAG
CCGCACAGGTGCCAGATGTTTTGCAACCAGACTGCCTGTCCAGCCGACTGCGACCCCAAC
ACCCAGGCTAGCTGTGAGTGCCCTGAAGGCTACATCCTGGACGACGGTTTCATCTGCACG
GACATCGACGAGTGCGAAAACGGCGGCTTCTGCTCCGGGGTGTGCCACAACCTCCCCGGT
ACCTTCGAGTGCATCTGCGGGCCCGACTCGGCCCTTGCCCGCCACATTGGCACCGACTGT
GACTCCGGCAAGGTGGACGGTGGCGACAGCGGCTCTGGCGAGCCCCCGCCCAGCCCGACG
CCCGGCTCCACCTTGACTCCTCCGGCCGTGGGGCTCGTGCATTCGGGCTTGCTCATAGGC
ATCTCCATCGCGAGCCTGTGCCTGGTGGTGGCGCTTTTGGCGCTCCTCTGCCACCTGCGC
AAGAAGCAGGGCGCCGCCAGGGCCAAGATGGAGTACAAGTGCGCGGCCCCTTCCAAGGAG
GTAGTGCTGCAGCACGTGCGGACCGAGCGGACGCCGCAGAGACTCTGA
GenBank Gene IDX05495
GeneCard IDNot Available
GenAtlas IDTHBD
HGNC IDHGNC:11784
Chromosome Location20
Locus20p12-cen
References
  1. Suzuki K, Kusumoto H, Deyashiki Y, Nishioka J, Maruyama I, Zushi M, Kawahara S, Honda G, Yamamoto S, Horiguchi S: Structure and expression of human thrombomodulin, a thrombin receptor on endothelium acting as a cofactor for protein C activation. EMBO J. 1987 Jul;6(7):1891-7. 2820710
  2. Wen DZ, Dittman WA, Ye RD, Deaven LL, Majerus PW, Sadler JE: Human thrombomodulin: complete cDNA sequence and chromosome localization of the gene. Biochemistry. 1987 Jul 14;26(14):4350-7. 2822087
  3. Jackman RW, Beeler DL, Fritze L, Soff G, Rosenberg RD: 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. 1987 Sep;84(18):6425-9. 2819876
  4. Shirai T, Shiojiri S, Ito H, Yamamoto S, Kusumoto H, Deyashiki Y, Maruyama I, Suzuki K: Gene structure of human thrombomodulin, a cofactor for thrombin-catalyzed activation of protein C. J Biochem. 1988 Feb;103(2):281-5. 2836377
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  7. Gerlitz B, Hassell T, Vlahos CJ, Parkinson JF, Bang NU, Grinnell BW: Identification of the predominant glycosaminoglycan-attachment site in soluble recombinant human thrombomodulin: potential regulation of functionality by glycosyltransferase competition for serine474. Biochem J. 1993 Oct 1;295 ( Pt 1):131-40. 8216207
  8. Yamamoto S, Mizoguchi T, Tamaki T, Ohkuchi M, Kimura S, Aoki N: Urinary thrombomodulin, its isolation and characterization. J Biochem. 1993 Apr;113(4):433-40. 8390446
  9. Adler M, Seto MH, Nitecki DE, Lin JH, Light DR, Morser J: The structure of a 19-residue fragment from the C-loop of the fourth epidermal growth factor-like domain of thrombomodulin. J Biol Chem. 1995 Oct 6;270(40):23366-72. 7559494
  10. Meininger DP, Hunter MJ, Komives EA: Synthesis, activity, and preliminary structure of the fourth EGF-like domain of thrombomodulin. Protein Sci. 1995 Sep;4(9):1683-95. 8528067
  11. Srinivasan J, Hu S, Hrabal R, Zhu Y, Komives EA, Ni F: Thrombin-bound structure of an EGF subdomain from human thrombomodulin determined by transferred nuclear Overhauser effects. Biochemistry. 1994 Nov 22;33(46):13553-60. 7947766
  12. Hrabal R, Komives EA, Ni F: Structural resiliency of an EGF-like subdomain bound to its target protein, thrombin. Protein Sci. 1996 Feb;5(2):195-203. 8745396
  13. Sampoli Benitez BA, Hunter MJ, Meininger DP, Komives EA: Structure of the fifth EGF-like domain of thrombomodulin: An EGF-like domain with a novel disulfide-bonding pattern. J Mol Biol. 1997 Nov 7;273(4):913-26. 9367781
  14. Ohlin AK, Marlar RA: The first mutation identified in the thrombomodulin gene in a 45-year-old man presenting with thromboembolic disease. Blood. 1995 Jan 15;85(2):330-6. 7811989
  15. Ohlin AK, Norlund L, Marlar RA: Thrombomodulin gene variations and thromboembolic disease. Thromb Haemost. 1997 Jul;78(1):396-400. 9198186
  16. Norlund L, Holm J, Zoller B, Ohlin AK: A common thrombomodulin amino acid dimorphism is associated with myocardial infarction. Thromb Haemost. 1997 Feb;77(2):248-51. 9157575
  17. Doggen CJ, Kunz G, Rosendaal FR, Lane DA, Vos HL, Stubbs PJ, Manger Cats V, Ireland H: A mutation in the thrombomodulin gene, 127G to A coding for Ala25Thr, and the risk of myocardial infarction in men. Thromb Haemost. 1998 Nov;80(5):743-8. 9843165
  18. Wu KK, Aleksic N, Ahn C, Boerwinkle E, Folsom AR, Juneja H: Thrombomodulin Ala455Val polymorphism and risk of coronary heart disease. Circulation. 2001 Mar 13;103(10):1386-9. 11245641
  19. Faioni EM, Franchi F, Castaman G, Biguzzi E, Rodeghiero F: Mutations in the thrombomodulin gene are rare in patients with severe thrombophilia. Br J Haematol. 2002 Aug;118(2):595-9. 12139752
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  21. Maga TK, Nishimura CJ, Weaver AE, Frees KL, Smith RJ: Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome. Hum Mutat. 2010 Jun;31(6):E1445-60. doi: 10.1002/humu.21256. 20513133