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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-04-16 16:48:16
Primary Accession Number DB01109
Secondary Accession Number
  • APRD00056
Name Heparin
Drug Type
  • Approved
  • Investigational
  • Small Molecule
Description Heparin, a highly sulfated glycosaminoglycan is widely used as an injectable anticoagulant. It has the highest negative charge density of any known biological molecule. Heparin acts as an anticoagulant, preventing the formation of clots and extension of existing clots within the blood. While heparin does not break down clots that have already formed, it allows the body's natural clot lysis mechanisms to work normally to break down clots that have already formed. Heparin binds to and accelerates the activity of antithrombin III. By activating antithrombin III, heparin preferentially potentiates the inhibition of coagulation factors Xa and IIa. Factor Xa catalyzes the conversion of prothrombin to thrombin, so heparin s inhibition of this process results in decreased thrombin and ultimately the prevention of fibrin clot formation.
Synonyms
  1. Alpha-Heparin
  2. Heparin sodium
  3. Heparin sodium preservative Free
  4. Heparin sodium salt
  5. Heparin sulfate
  6. Heparinate
  7. Heparinic acid
  8. Low molecular weight heparin sodium
  9. Sodium heparin
  10. heparin
  11. liquid
  12. oral
Brand Names
  1. Ariven
  2. Arteven
  3. Bemiparin
  4. Calcilean
  5. Calciparine
  6. Certoparin
  7. Clexane
  8. Clivarin
  9. Clivarine
  10. Dalteparin
  11. Depo-Heparin
  12. Eparina [DCIT]
  13. Fluxum
  14. Fragmin A
  15. Fragmin B
  16. Fraxiparin
  17. Hed-Heparin
  18. Hepalean
  19. Heparin Cy 216
  20. Heparin Leo
  21. Heparin Lock Flush
  22. Hepathrom
  23. Leparan
  24. Lipo-Hepin
  25. Liquaemin
  26. Liquaemin Sodium
  27. Liquemin
  28. Multiparin
  29. Novoheparin
  30. Pabyrin
  31. Parnaparin
  32. Parvoparin
  33. Pularin
  34. Reviparin
  35. Sandoparin
  36. Sublingula
  37. Thromboliquine
  38. Vetren
  39. Vitrum AB
Brand Mixtures Not Available
Chemical IUPAC Name 6-[5-acetamido-4,6-dihydroxy-2-(sulfooxymethyl)oxan-3-yl]oxy-3-[5-(6-carboxy-4,5-dihydroxy-3-sulfooxyoxan-2-yl)oxy-6-(hydroxymethyl)-3-(sulfoamino)-4-sulfooxyoxan-2-yl]oxy-4-hydroxy-5-sulfooxyoxane-2-carboxylic acid
Chemical Formula C26H42N2O37S5
Chemical Structure Structure
CAS Registry Number 9005-49-6
InChI Identifier InChI=1/C26H42N2O37S5/c1-4(30)27-7-9(31)13(6(56-23(7)39)3-55-67(43,44)45)58-26-19(65-70(52,53)54)12(34)16(20(62-26)22(37)38)60-24-8(28-66(40,41)42)15(63-68(46,47)48)14(5(2-29)57-24)59-25-18(64-69(49,50)51)11(33)10(32)17(61-25)21(35)36/h5-20,23-26,28-29,31-34,39H,2-3H2,1H3,(H,27,30)(H,35,36)(H,37,38)(H,40,41,42)(H,43,44,45)(H,46,47,48)(H,49,50,51)(H,52,53,54)/f/h27,35,37,40,43,46,49,52H
InChI Key HTTJABKRGRZYRN-XKAJDVGVCI
KEGG Drug Not Available
KEGG Compound C00374 Link Image
PubChem Compound 772 Link Image
PubChem Substance 2789 Link Image
ChEBI ID 28304 Link Image
PharmGKB ID PA449855 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 00453781 Link Image
RxList Link http://www.rxlist.com/cgi/generic/heparin.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Heparin Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 1134.9280
Monoisotopic Molecular Weight 1134.0070
State Solid
Melting Point Not Available
Experimental Water Solubility Soluble Source: PhysProp
Predicted Water Solubility 1.08e+01 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity -13.2 Source: PhysProp
Predicted LogP -1.67 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -2.02 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID 1JVQ Link Image
Experimental PDB File Show
Experimental PDB Structure
Isomeric SMILES CC(=O)N[C@H]1[C@H](O)O[C@@H](COS(O)(=O)=O)[C@@H](O[C@@H]2O[C@@H]([C@@H](O[C@@H]3O[C@H](CO)[C@@H](O[C@H]4O[C@H]([C@H](O)[C@@H](O)[C@@H]4OS(O)(=O)=O)C(O)=O)[C@H](OS(O)(=O)=O)[C@H]3NS(O)(=O)=O)[C@H](O)[C@H]2OS(O)(=O)=O)C(O)=O)[C@@H]1O
Canonical SMILES CC(=O)NC1C(O)OC(COS(O)(=O)=O)C(OC2OC(C(OC3OC(CO)C(OC4OC(C(O)C(O)C4OS(O)(=O)=O)C(O)=O)C(OS(O)(=O)=O)C3NS(O)(=O)=O)C(O)C2OS(O)(=O)=O)C(O)=O)C1O
Drug Category
  • Anticoagulants
  • Fibrinolytic Agents
  • Heparins
ATC Codes
AHFS Codes
  • 20:12.04.16
  • 92:00.00
Indication For anticoagulant therapy in prophylaxis and treatment of venous thrombosis and its extension, for prevention of post-operative deep venous thrombosis and pulmonary embolism and for the prevention of clotting in arterial and cardiac surgery.
Pharmacology Heparin is a highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Heparin is a well known and commonly used anticoagulant which has antithrombotic properties. Heparin is indicated for the prophylaxis of deep vein thrombosis, which may lead to pulmonary embolism, and also for the prophylaxis of ischemic complications of unstable angina and non-Q-wave myocardial infarction, when concurrently administered with aspirin. Heparin inhibits reactions that lead to the clotting of blood and the formation of fibrin clots both in vitro and in vivo. Heparin acts at multiple sites in the normal coagulation system. Small amounts of Heparin in combination with antithrombin III (Heparin cofactor) can inhibit thrombosis by inactivating activated Factor X and inhibiting the conversion of prothrombin to thrombin. Once active thrombosis has developed, larger amounts of heparin can inhibit further coagulation by inactivating thrombin and preventing the conversion of fibrinogen to fibrin. Heparin also prevents the formation of a stable fibrin clot by inhibiting the activation of the fibrin stabilizing factor.
Mechanism of Action The mechanism of action of heparin is antithrombin-dependent. It acts mainly by accelerating the rate of the neutralization of certain activated coagulation factors by antithrombin, but other mechanisms may also be involved. The antithrombotic effect of heparin is well correlated to the inhibition of factor Xa. Heparin interacts with antithrombin III, prothrombin and factor X.
Absorption Some oral absorption but lack of anticoagulant effect. Rapidly taken up by endothelial cells with remainder bound to plasma proteins.
Toxicity Heparin sodium - Mouse, median lethal dose greater than 5000 mg/kg. Another side effect is heparin induced thrombocytopenia (HIT syndrome). HIT is caused by an immunological reaction that makes platelets form clots within the blood vessels, thereby using up coagulation factors
Protein Binding Very high, mostly to low-density lipoproteins
Biotransformation Liver and the reticulo-endothelial system are the sites of biotransformation.
Half Life 1.5 hours
Dosage Forms
Form Route
Liquid Intravenous
Liquid Irrigation
Solution Intraperitoneal
Solution Intravenous
Solution Subcutaneous
Patient Information Not Available
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Aspirin Association of ASA/Heparin increases risk of bleeding
Drospirenone Increased risk of hyperkaliemia
Food Interactions
  • Adequate calcium intake is recommended, needs increased with long term use, supplement recommended.
Pathways
Name SMPDB Link KEGG Link
Heparin Pathway SMP00274 Link Image
General References
  1. Petitou M, Herault JP, Bernat A, Driguez PA, Duchaussoy P, Lormeau JC, Herbert JM: Synthesis of thrombin-inhibiting heparin mimetics without side effects. Nature. 1999 Apr 1;398(6726):417-22. [PubMed Link Image]
  2. Linhardt RJ, Gunay NS: Production and chemical processing of low molecular weight heparins. Semin Thromb Hemost. 1999;25 Suppl 3:5-16. [PubMed Link Image]
  3. Hirsh J, Raschke R: Heparin and low-molecular-weight heparin: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):188S-203S. [PubMed Link Image]
  4. Ferro DR, Provasoli A, Ragazzi M, Casu B, Torri G, Bossennec V, Perly B, Sinay P, Petitou M, Choay J: Conformer populations of L-iduronic acid residues in glycosaminoglycan sequences. Carbohydr Res. 1990 Jan 15;195(2):157-67. [PubMed Link Image]
  5. Mulloy B, Forster MJ, Jones C, Davies DB: N.m.r. and molecular-modelling studies of the solution conformation of heparin. Biochem J. 1993 Aug 1;293 ( Pt 3):849-58. [PubMed Link Image]
  6. Drugs.com Link Image
  7. Wikipedia Link Image
  8. RxList Link Image
Organisms Affected
  • Humans and other mammals
Targets
  1. Prothrombin
  2. Coagulation factor X
  3. Antithrombin-III
  4. Coagulation factor IX
  5. Heparanase
  6. P-selectin
Drug Target 1 [top]
Target 1 ID 54
Target 1 Name Prothrombin
Target 1 Synonyms
  1. Activated Factor II [IIa]
  2. Coagulation factor II
  3. EC 3.4.21.5
  4. Prothrombin precursor
  5. Thrombin
Target 1 Gene Name F2
Target 1 Protein Sequence >Prothrombin precursor 
MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLEREC
VEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGTNYRGHV
NITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYTTDPTVRRQE
CSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVTTHGLPCLAWASA
QAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGYCDLNYCEEAVEEETG
DGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLFEKKSLEDKTERELLESYI
DGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFTEN
DLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDIALMKLKKPVAFSDYIHP
VCLPDRETAASLLQAGYKGRVTGWGNLKETWTANVGKGQPSVLQVVNLPIVERPVCKDST
RIRITDNMFCAGYKPDEGKRGDACEGDSGGPFVMKSPFNNRWYQMGIVSWGEGCDRDGKY
GFYTHVFRLKKWIQKVIDQFGE
Target 1 Number of Residues 632
Target 1 Molecular Weight 70037
Target 1 Theoretical pI 5.70
Target 1 GO Classification
Function
thrombin activity
binding
ion binding
cation binding
calcium ion binding
catalytic activity
hydrolase activity
peptidase activity
endopeptidase activity
serine-type endopeptidase activity
Process
organismal physiological process
regulation of body fluids
hemostasis
blood coagulation
physiological process
metabolism
macromolecule metabolism
protein metabolism
cellular protein metabolism
proteolysis
Component
extracellular region
Target 1 General Function Involved in blood clotting cascade
Target 1 Specific Function Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C
Target 1 Pathways Not Available
Target 1 Reactions
  • Selective cleavage of Arg!Gly bonds in fibrinogen to form fibrin and release fibrinopeptides A and B INHIBITOR Benzamidine; D-Phe-Pro-Arg-CH2Cl; Nalpha-(2-naphthyl-sulfonyl-glycyl)-D-p-amidinopheyl-alanylpiperadin e; Argatroban
Target 1 Pfam Domain Function
Target 1 Signals
  • 1-24
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 339641 Link Image
Target 1 UniProtKB/Swiss-Prot ID P00734 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name THRB_HUMAN Link Image
Target 1 PDB ID 1HAG Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Secreted protein
  • extracellular space
Target 1 Gene Sequence >1869 bp 
ATGGCGCACGTCCGAGGCTTGCAGCTGCCTGGCTGCCTGGCCCTGGCTGCCCTGTGTAGC
CTTGTGCACAGCCAGCATGTGTTCCTGGCTCCTCAGCAAGCACGGTCGCTGCTCCAGCGG
GTCCGGCGAGCCAACACCTTCTTGGAGGAGGTGCGCAAGGGCAACCTAGAGCGAGAGTGC
GTGGAGGAGACGTGCAGCTACGAGGAGGCCTTCGAGGCTCTGGAGTCCTCCACGGCTACG
GATGTGTTCTGGGCCAAGTACACAGCTTGTGAGACAGCGAGGACGCCTCGAGATAAGCTT
GCTGCATGTCTGGAAGGTAACTGTGCTGAGGGTCTGGGTACGAACTACCGAGGGCATGTG
AACATCACCCGGTCAGGCATTGAGTGCCAGCTATGGAGGAGTCGCTACCCACATAAGCCT
GAAATCAACTCCACTACCCATCCTGGGGCCGACCTACAGGAGAATTTCTGCCGCAACCCC
GACAGCAGCACCACGGGACCCTGGTGCTACACTACAGACCCCACCGTGAGGAGGCAGGAA
TGCAGCATCCCTGTCTGTGGCCAGGATCAAGTCACTGTAGCGATGACTCCACGCTCCGAA
GGCTCCAGTGTGAATCTGTCACCTCCATTGGAGCAGTGTGTCCCTGATCGGGGGCAGCAG
TACCAGGGGCGCCTGGCGGTGACCACACATGGGCTCCCCTGCCTGGCCTGGGCCAGCGCA
CAGGCCAAGGCCCTGAGCAAGCACCAGGACTTCAACTCAGCTGTGCAGCTGGTGGAGAAC
TTCTGCCGCAACCCAGACGGGGATGAGGAGGGCGTGTGGTGCTATGTGGCCGGGAAGCCT
GGCGACTTTGGGTACTGCGACCTCAACTATTGTGAGGAGGCCGTGGAGGAGGAGACAGGA
GATGGGCTGGATGAGGACTCAGACAGGGCCATCGAAGGGCGTACCGCCACCAGTGAGTAC
CAGACTTTCTTCAATCCGAGGACCTTTGGCTCGGGAGAGGCAGACTGTGGGCTGCGACCT
CTGTTCGAGAAGAAGTCGCTGGAGGACAAAACCGAAAGAGAGCTCCTGGAATCCTACATC
GACGGGCGCATTGTGGAGGGCTCGGATGCAGAGATCGGCATGTCACCTTGGCAGGTGATG
CTTTTCCGGAAGAGTCCCCAGGAGCTGCTGTGTGGGGCCAGCCTCATCAGTGACCGCTGG
GTCCTCACCGCCGCCCACTGCCTCCTGTACCCGCCCTGGGACAAGAACTTCACCGAGAAT
GACCTTCTGGTGCGCATTGGCAAGCACTCCCGCACAAGGTACGAGCGAAACATTGAAAAG
ATATCCATGTTGGAAAAGATCTACATCCACCCCAGGTACAACTGGCGGGAGAACCTGGAC
CGGGACATTGCCCTGATGAAGCTGAAGAAGCCTGTTGCCTTCAGTGACTACATTCACCCT
GTGTGTCTGCCCGACAGGGAGACGGCAGCCAGCTTGCTCCAGGCTGGATACAAGGGGCGG
GTGACAGGCTGGGGCAACCTGAAGGAGACGTGGACAGCCAACGTTGGTAAGGGGCAGCCC
AGTGTCCTGCAGGTGGTGAACCTGCCCATTGTGGAGCGGCCGGTCTGCAAGGACTCCACC
CGGATCCGCATCACTGACAACATGTTCTGTGCTGGTTACAAGCCTGATGAAGGGAAACGA
GGGGATGCCTGTGAAGGTGACAGTGGGGGACCCTTTGTCATGAAGAGCCCCTTTAACAAC
CGCTGGTATCAAATGGGCATCGTCTCATGGGGTGAAGGCTGTGACCGGGATGGGAAATAT
GGCTTCTACACACATGTGTTCCGCCTGAAGAAGTGGATACAGAAGGTCATTGATCAGTTT
GGAGAGTAG
Target 1 GenBank Gene ID
Target 1 GeneCard ID F2 Link Image
Target 1 GenAtlas ID F2 Link Image
Target 1 HGNC ID HGNC:3535 Link Image
Target 1 Chromosome Location 11
Target 1 Locus 11p11-q12
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Guinto ER, Caccia S, Rose T, Futterer K, Waksman G, Di Cera E: Unexpected crucial role of residue 225 in serine proteases. Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):1852-7. [PubMed Link Image]
  2. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed Link Image]
  3. Iwahana H, Yoshimoto K, Shigekiyo T, Shirakami A, Saito S, Itakura M: Detection of a single base substitution of the gene for prothrombin Tokushima. The application of PCR-SSCP for the genetic and molecular analysis of dysprothrombinemia. Int J Hematol. 1992 Feb;55(1):93-100. [PubMed Link Image]
  4. Miyata T, Aruga R, Umeyama H, Bezeaud A, Guillin MC, Iwanaga S: Prothrombin Salakta: substitution of glutamic acid-466 by alanine reduces the fibrinogen clotting activity and the esterase activity. Biochemistry. 1992 Aug 25;31(33):7457-62. [PubMed Link Image]
  5. Morishita E, Saito M, Kumabashiri I, Asakura H, Matsuda T, Yamaguchi K: Prothrombin Himi: a compound heterozygote for two dysfunctional prothrombin molecules (Met-337-->Thr and Arg-388-->His). Blood. 1992 Nov 1;80(9):2275-80. [PubMed Link Image]
  6. Rydel TJ, Ravichandran KG, Tulinsky A, Bode W, Huber R, Roitsch C, Fenton JW 2nd: The structure of a complex of recombinant hirudin and human alpha-thrombin. Science. 1990 Jul 20;249(4966):277-80. [PubMed Link Image]
  7. Bode W, Mayr I, Baumann U, Huber R, Stone SR, Hofsteenge J: The refined 1.9 A crystal structure of human alpha-thrombin: interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment. EMBO J. 1989 Nov;8(11):3467-75. [PubMed Link Image]
  8. Walz DA, Hewett-Emmett D, Seegers WH: Amino acid sequence of human prothrombin fragments 1 and 2. Proc Natl Acad Sci U S A. 1977 May;74(5):1969-72. [PubMed Link Image]
  9. Henriksen RA, Mann KG: Substitution of valine for glycine-558 in the congenital dysthrombin thrombin Quick II alters primary substrate specificity. Biochemistry. 1989 Mar 7;28(5):2078-82. [PubMed Link Image]
  10. Degen SJ, Davie EW: Nucleotide sequence of the gene for human prothrombin. Biochemistry. 1987 Sep 22;26(19):6165-77. [PubMed Link Image]
  11. 3242619 Henriksen RA, Mann KG: Identification of the primary structural defect in the dysthrombin thrombin Quick I: substitution of cysteine for arginine-382. Biochemistry. 1988 Dec 27;27(26):9160-5.
  12. 3567158 Miyata T, Morita T, Inomoto T, Kawauchi S, Shirakami A, Iwanaga S: Prothrombin Tokushima, a replacement of arginine-418 by tryptophan that impairs the fibrinogen clotting activity of derived thrombin Tokushima. Biochemistry. 1987 Feb 24;26(4):1117-22.
  13. 3759958 Rabiet MJ, Blashill A, Furie B, Furie BC: Prothrombin fragment 1 X 2 X 3, a major product of prothrombin activation in human plasma. J Biol Chem. 1986 Oct 5;261(28):13210-5.
  14. 3771562 Rabiet MJ, Furie BC, Furie B: Molecular defect of prothrombin Barcelona. Substitution of cysteine for arginine at residue 273. J Biol Chem. 1986 Nov 15;261(32):15045-8.
  15. 3801671 Inomoto T, Shirakami A, Kawauchi S, Shigekiyo T, Saito S, Miyoshi K, Morita T, Iwanaga S: Prothrombin Tokushima: characterization of dysfunctional thrombin derived from a variant of human prothrombin. Blood. 1987 Feb;69(2):565-9.
  16. 6305407 Degen SJ, MacGillivray RT, Davie EW: Characterization of the complementary deoxyribonucleic acid and gene coding for human prothrombin. Biochemistry. 1983 Apr 26;22(9):2087-97.
  17. 6405779 Board PG, Shaw DC: Determination of the amino acid substitution in human prothrombin type 3 (157 Glu leads to Lys) and the localization of a third thrombin cleavage site. Br J Haematol. 1983 Jun;54(2):245-54.
  18. 7792730 Degen SJ, McDowell SA, Sparks LM, Scharrer I: Prothrombin Frankfurt: a dysfunctional prothrombin characterized by substitution of Glu-466 by Ala. Thromb Haemost. 1995 Feb;73(2):203-9.
  19. 7865694 James HL, Kim DJ, Zheng DQ, Girolami A: Prothrombin Padua I: incomplete activation due to an amino acid substitution at a factor Xa cleavage site. Blood Coagul Fibrinolysis. 1994 Oct;5(5):841-4.
  20. 8071320 Rydel TJ, Yin M, Padmanabhan KP, Blankenship DT, Cardin AD, Correa PE, Fenton JW 2nd, Tulinsky A: Crystallographic structure of human gamma-thrombin. J Biol Chem. 1994 Sep 2;269(35):22000-6.
  21. 873923 Butkowski RJ, Elion J, Downing MR, Mann KG: Primary structure of human prethrombin 2 and alpha-thrombin. J Biol Chem. 1977 Jul 25;252(14):4942-57.
  22. 9214615 van de Locht A, Bode W, Huber R, Le Bonniec BF, Stone SR, Esmon CT, Stubbs MT: The thrombin E192Q-BPTI complex reveals gross structural rearrangements: implications for the interaction with antithrombin and thrombomodulin. EMBO J. 1997 Jun 2;16(11):2977-84.
Target 1 Drug References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
  2. Fuster V: [Oral antithrombins and the future of antithrombotic therapy] Rev Esp Cardiol. 2004;57 Suppl 1:2-8. [PubMed Link Image]
  3. Hansen PR: [Bivalirudin: a direct thrombin inhibitor in percutaneous coronary interventions] Ugeskr Laeger. 2006 Sep 18;168(38):3207-9. [PubMed Link Image]
  4. Grudzinski L, Quinan P, Kwok S, Pierratos A: Sodium citrate 4% locking solution for central venous dialysis catheters--an effective, more cost-efficient alternative to heparin. Nephrol Dial Transplant. 2007 Feb;22(2):471-6. Epub 2006 Oct 25. [PubMed Link Image]
  5. Keller TT, van der Sluijs KF, de Kruif MD, Gerdes VE, Meijers JC, Florquin S, van der Poll T, van Gorp EC, Brandjes DP, Buller HR, Levi M: Effects on coagulation and fibrinolysis induced by influenza in mice with a reduced capacity to generate activated protein C and a deficiency in plasminogen activator inhibitor type 1. Circ Res. 2006 Nov 24;99(11):1261-9. Epub 2006 Oct 26. [PubMed Link Image]
  6. Li N, He S, Blomback M, Hjemdahl P: Platelet activity, coagulation, and fibrinolysis during exercise in healthy males: effects of thrombin inhibition by argatroban and enoxaparin. Arterioscler Thromb Vasc Biol. 2007 Feb;27(2):407-13. Epub 2006 Nov 30. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 239
Target 2 Name Coagulation factor X
Target 2 Synonyms
  1. Coagulation factor X precursor
  2. EC 3.4.21.6
  3. Stuart factor
  4. Stuart- Prower factor
Target 2 Gene Name F10
Target 2 Protein Sequence >Coagulation factor X precursor 
MGRPLHLVLLSASLAGLLLLGESLFIRREQANNILARVTRANSFLEEMKKGHLERECMEE
TCSYEEAREVFEDSDKTNEFWNKYKDGDQCETSPCQNQGKCKDGLGEYTCTCLEGFEGKN
CELFTRKLCSLDNGDCDQFCHEEQNSVVCSCARGYTLADNGKACIPTGPYPCGKQTLERR
KRSVAQATSSSGEAPDSITWKPYDAADLDPTENPFDLLDFNQTQPERGDNNLTRIVGGQE
CKDGECPWQALLINEENEGFCGGTILSEFYILTAAHCLYQAKRFKVRVGDRNTEQEEGGE
AVHEVEVVIKHNRFTKETYDFDIAVLRLKTPITFRMNVAPACLPERDWAESTLMTQKTGI
VSGFGRTHEKGRQSTRLKMLEVPYVDRNSCKLSSSFIITQNMFCAGYDTKQEDACQGDSG
GPHVTRFKDTYFVTGIVSWGEGCARKGKYGIYTKVTAFLKWIDRSMKTRGLPKAKSHAPE
VITSSPLK
Target 2 Number of Residues 496
Target 2 Molecular Weight 54732
Target 2 Theoretical pI 5.74
Target 2 GO Classification
Function
catalytic activity
hydrolase activity
peptidase activity
endopeptidase activity
serine-type endopeptidase activity
binding
ion binding
cation binding
calcium ion binding
Process
metabolism
macromolecule metabolism
protein metabolism
cellular protein metabolism
proteolysis
physiological process
organismal physiological process
regulation of body fluids
hemostasis
blood coagulation
Component
extracellular region
Target 2 General Function Involved in calcium ion binding
Target 2 Specific Function Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting
Target 2 Pathways Not Available
Target 2 Reactions
  • Selective cleavage of Arg!Thr and then Arg!Ile bonds in prothrombin to form thrombin
Target 2 Pfam Domain Function
Target 2 Signals
  • 1-31
Target 2 Transmembrane Regions
  • 7-26
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 182841 Link Image
Target 2 UniProtKB/Swiss-Prot ID P00742 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name FA10_HUMAN Link Image
Target 2 PDB ID 1P0S Link Image
Target 2 PDB File Show
Target 2 3D Structure
Target 2 Cellular Location
  • Cytoplasmic
Target 2 Gene Sequence >1433 bp 
CCTCCCTGGCTGGCCTCCTGCTGCTCGGGGAAAGTCTGTTCATCCGCAGGGAGCAGGCCA
ACAACATCCTGGCGAGGGTCACGAGGGCCAATTCCTTTCTTGAAGAGATGAAGAAAGGAC
ACCTCGAAAGAGAGTGCATGGAAGAGACCTGCTCATACGAAGAGGCCCGCGAGGTCTTTG
AGGACAGCGACAAGACGAATGAATTCTGGAATAAATACAAAGATGGCGACCAGTGTGAGA
CCAGTCCTTGCCAGAACCAGGGCAAATGTAAAGACGGCCTCGGGGAATACACCTGCACCT
GTTTAGAAGGATTCGAAGGCAAAAACTGTGAATTATTCACACGGAAGCTCTGCAGCCTGG
ACAACGGGGACTGTGACCAGTTCTGCCACGAGGAACAGAACTCTGTGGTGTGCTCCTGCG
CCCGCGGGTACACCCTGGCTGACAACGGCAAGGCCTGCATTCCCACAGGGCCCTACCCCT
GTGGGAAACAGACCCTGGAACGCAGGAAGAGGTCAGTGGCCCAGGCCACCAGCAGCAGCG
GGGAGGCCCCTGACAGCATCACATGGAAGCCATATGATGCAGCCGACCTGGACCCCACCG
AGAACCCCTTCGACCTGCTTGACTTCAACCAGACGCAGCCTGAGAGGGGCGACAACAACC
TCACCAGGATCGTGGGAGGCCAGGAATGCAAGGACGGGGAGTGTCCCTGGCAGGCCCTGC
TCATCAATGAGGAAAACGAGGGTTTCTGTGGTGGAACTATTCTGAGCGAGTTCTACATCC
TAACGGCAGCCCACTGTCTCTACCAAGCCAAGAGATTCAAGGTGAGGGTAGGGGACCGGA
ACACGGAGCAGGAGGAGGGCGGTGAGGCGGTGCACGAGGTGGAGGTGGTCATCAAGCACA
ACCGGTTCACAAAGGAGACCTATGACTTCGACATCGCCGTGCTCCGGCTCAAGACCCCCA
TCACCTTCCGCATGAACGTGGCGCCTGCCTGCCTCCCCGAGCGTGACTGGGCCGAGTCCA
CGCTGATGACGCAGAAGACGGGGATTGTGAGCGGCTTCGGGCGCACCCACGAGAAGGGCC
GGCAGTCCACCAGGCTCAAGATGCTGGAGGTGCCCTACGTGGACCGCAACAGCTGCAAGC
TGTCCAGCAGCTTCATCATCACCCAGAACATGTTCTGTGCCGGCTACGACACCAAGCAGG
AGGATGCCTGCCAGGGGGACAGCGGGGGCCCGCACGTCACCCGCTTCAAGGACACCTACT
TCGTGACAGGCATCGTCAGCTGGGGAGAGAGCTGTGCCCGTAAGGGGAAGTACGGGATCT
ACACCAAGGTCACCGCCTTCCTCAAGTGGATCGACAGGTCCATGAAAACCAGGGGCTTGC
CCAAGGCCAAGAGCCATGCCCCGGAGGTCATAACGTCCTCTCCATTAAAGTGA
Target 2 GenBank Gene ID
Target 2 GeneCard ID F10 Link Image
Target 2 GenAtlas ID F10 Link Image
Target 2 HGNC ID HGNC:3528 Link Image
Target 2 Chromosome Location 13
Target 2 Locus 13q34
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed Link Image]
  2. Messier TL, Pittman DD, Long GL, Kaufman RJ, Church WR: Cloning and expression in COS-1 cells of a full-length cDNA encoding human coagulation factor X. Gene. 1991 Mar 15;99(2):291-4. [PubMed Link Image]
  3. Fung MR, Hay CW, MacGillivray RT: Characterization of an almost full-length cDNA coding for human blood coagulation factor X. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3591-5. [PubMed Link Image]
  4. Jagadeeswaran P, Reddy SV, Rao KJ, Hamsabhushanam K, Lyman G: Cloning and characterization of the 5' end (exon 1) of the gene encoding human factor X. Gene. 1989 Dec 14;84(2):517-9. [PubMed Link Image]
  5. Kaul RK, Hildebrand B, Roberts S, Jagadeeswaran P: Isolation and characterization of human blood-coagulation factor X cDNA. Gene. 1986;41(2-3):311-4. [PubMed Link Image]
  6. Leytus SP, Foster DC, Kurachi K, Davie EW: Gene for human factor X: a blood coagulation factor whose gene organization is essentially identical with that of factor IX and protein C. Biochemistry. 1986 Sep 9;25(18):5098-102. [PubMed Link Image]
  7. Leytus SP, Chung DW, Kisiel W, Kurachi K, Davie EW: Characterization of a cDNA coding for human factor X. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3699-702. [PubMed Link Image]
  8. McMullen BA, Fujikawa K, Kisiel W, Sasagawa T, Howald WN, Kwa EY, Weinstein B: Complete amino acid sequence of the light chain of human blood coagulation factor X: evidence for identification of residue 63 as beta-hydroxyaspartic acid. Biochemistry. 1983 Jun 7;22(12):2875-84. [PubMed Link Image]
  9. Inoue K, Morita T: Identification of O-linked oligosaccharide chains in the activation peptides of blood coagulation factor X. The role of the carbohydrate moieties in the activation of factor X. Eur J Biochem. 1993 Nov 15;218(1):153-63. [PubMed Link Image]
  10. Padmanabhan K, Padmanabhan KP, Tulinsky A, Park CH, Bode W, Huber R, Blankenship DT, Cardin AD, Kisiel W: Structure of human des(1-45) factor Xa at 2.2 A resolution. J Mol Biol. 1993 Aug 5;232(3):947-66. [PubMed Link Image]
  11. 9618463 Kamata K, Kawamoto H, Honma T, Iwama T, Kim SH: Structural basis for chemical inhibition of human blood coagulation factor Xa. Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6630-5.
Target 2 Drug References
  1. Patey SJ, Edwards EA, Yates EA, Turnbull JE: Heparin derivatives as inhibitors of BACE-1, the Alzheimer's beta-secretase, with reduced activity against factor Xa and other proteases. J Med Chem. 2006 Oct 5;49(20):6129-32. [PubMed Link Image]
  2. Ignjatovic V, Summerhayes R, Gan A, Than J, Chan A, Cochrane A, Bennett M, Horton S, Shann F, Lane G, Ross-Smith M, Monagle P: Monitoring Unfractionated Heparin (UFH) therapy: which Anti-Factor Xa assay is appropriate? Thromb Res. 2007;120(3):347-51. Epub 2006 Nov 21. [PubMed Link Image]
  3. Graff J, Picard-Willems B, Harder S: Monitoring effects of direct FXa-inhibitors with a new one-step prothrombinase-induced clotting time (PiCT) assay: comparative in vitro investigation with heparin, enoxaparin, fondaparinux and DX 9065a. Int J Clin Pharmacol Ther. 2007 Apr;45(4):237-43. [PubMed Link Image]
  4. Berges A, Laporte S, Epinat M, Zufferey P, Alamartine E, Tranchand B, Decousus H, Mismetti P: Anti-factor Xa activity of enoxaparin administered at prophylactic dosage to patients over 75 years old. Br J Clin Pharmacol. 2007 Oct;64(4):428-38. Epub 2007 May 17. [PubMed Link Image]
  5. Paige JT, Gouda BP, Gaitor-Stampley V, Scalia PG, Klainer TE, Raum WJ, Martin LF: No correlation between anti-factor Xa levels, low-molecular-weight heparin, and bleeding after gastric bypass. Surg Obes Relat Dis. 2007 Jul-Aug;3(4):469-75. Epub 2007 Jun 12. [PubMed Link Image]
Drug Target 3 [top]
Target 3 ID 309
Target 3 Name Antithrombin-III
Target 3 Synonyms
  1. ATIII
  2. Antithrombin-III precursor
Target 3 Gene Name SERPINC1
Target 3 Protein Sequence >Antithrombin-III precursor 
MYSNVIGTVTSGKRKVYLLSLLLIGFWDCVTCHGSPVDICTAKPRDIPMNPMCIYRSPEK
KATEDEGSEQKIPEATNRRVWELSKANSRFATTFYQHLADSKNDNDNIFLSPLSISTAFA
MTKLGACNDTLQQLMEVFKFDTISEKTSDQIHFFFAKLNCRLYRKANKSSKLVSANRLFG
DKSLTFNETYQDISELVYGAKLQPLDFKENAEQSRAAINKWVSNKTEGRITDVIPSEAIN
ELTVLVLVNTIYFKGLWKSKFSPENTRKELFYKADGESCSASMMYQEGKFRYRRVAEGTQ
VLELPFKGDDITMVLILPKPEKSLAKVEKELTPEVLQEWLDELEEMMLVVHMPRFRIEDG
FSLKEQLQDMGLVDLFSPEKSKLPGIVAEGRDDLYVSDAFHKAFLEVNEEGSEAAASTAV
VIAGRSLNPNRVTFKANRPFLVFIREVPLNTIIFMGRVANPCVK
Target 3 Number of Residues 471
Target 3 Molecular Weight 52603
Target 3 Theoretical pI 6.68
Target 3 GO Classification
Function
enzyme regulator activity
enzyme inhibitor activity
protease inhibitor activity
endopeptidase inhibitor activity
serine-type endopeptidase inhibitor activity
Process
Not Available
Component
Not Available
Target 3 General Function Involved in serine-type endopeptidase inhibitor activity
Target 3 Specific Function Most important serine protease inhibitor in plasma that regulates the blood coagulation cascade. AT-III inhibits thrombin as well as factors IXa, Xa and XIa. Its inhibitory activity is greatly enhanced in the presence of heparin
Target 3 Pathways Not Available
Target 3 Reactions Not Available
Target 3 Pfam Domain Function
Target 3 Signals
  • 1-32
Target 3 Transmembrane Regions
  • None
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 179161 Link Image
Target 3 UniProtKB/Swiss-Prot ID P01008 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name ANT3_HUMAN Link Image
Target 3 PDB ID 1JVQ Link Image
Target 3 PDB File Show
Target 3 3D Structure
Target 3 Cellular Location
  • Secreted protein
  • extracellular space
Target 3 Gene Sequence >1395 bp 
ATGTATTCCAATGTGATAGGAACTGTAACCTCTGGAAAAAGGAAGGTTTATCTTTTGTCC
TTGCTGCTCATTGGCTTCTGGGACTGCGTGACCTGTCACGGGAGCCCTGTGGACATCTGC
ACAGCCAAGCCGCGGGACATTCCCATGAATCCCATGTGCATTTACCGCTCCCCGGAGAAG
AAGGCAACTGAGGATGAGGGCTCAGAACAGAAGATCCCGGAGGCCACCAACCGGCGTGTC
TGGGAACTGTCCAAGGCCAATTCCCGCTTTGCTACCACTTTCTATCAGCACCTGGCAGAT
TCCAAGAATGACAATGATAACATTTTCCTGTCACCCCTGAGTATCTCCACGGCTTTTGCT
ATGACCAAGCTGGGTGCCTGTAATGACACCCTCCAGCAACTGATGGAGGTATTTAAGTTT
GACACCATATCTGAGAAAACATCTGATCAGATCCACTTCTTCTTTGCCAAACTGAACTGC
CGACTCTATCGAAAAGCCAACAAATCCTCCAAGTTAGTATCAGCCAATCGCCTTTTTGGA
GACAAATCCCTTACCTTCAATGAGACCTACCAGGACATCAGTGAGTTGGTATATGGAGCC
AAGCTCCAGCCCCTGGACTTCAAGGAAAATGCAGAGCAATCCAGAGCGGCCATCAACAAA
TGGGTGTCCAATAAGACCGAAGGCCGAATCACCGATGTCATTCCCTCGGAAGCCATCAAT
GAGCTCACTGTTCTGGTGCTGGTTAACACCATTTACTTCAAGGGCCTGTGGAAGTCAAAG
TTCAGCCCTGAGAACACAAGGAAGGAACTGTTCTACAAGGCTGATGGAGAGTCGTGTTCA
GCATCTATGATGTACCAGGAAGGCAAGTTCCGTTATCGGCGCGTGGCTGAAGGCACCCAG
GTGCTTGAGTTGCCCTTCAAAGGTGATGACATCACCATGGTCCTCATCTTGCCCAAGCCT
GAGAAGAGCCTGGCCAAGGTGGAGAAGGAACTCACCCCAGAGGTGCTGCAGGAGTGGCTG
GATGAATTGGAGGAGATGATGCTGGTGGTCCACATGCCCCGCTTCCGCATTGAGGACGGC
TTCAGTTTGAAGGAGCAGCTGCAAGACATGGGCCTTGTCGATCTGTTCAGCCCTGAAAAG
TCCAAACTCCCAGGTATTGTTGCAGAAGGCCGAGATGACCTCTATGTCTCAGATGCATTC
CATAAGGCATTTCTTGAGGTAAATGAAGAAGGCAGTGAAGCAGCTGCAAGTACCGCTGTT
GTGATTGCTGGCCGTTCGCTAAACCCCAACAGGGTGACTTTCAAGGCCAACAGGCTTTTC
CTGGTTTTTATAAGAGAAGTTCCTCTGAACACTATTATCTTCATGGGCAGAGTAGCCAAC
CCTTGTGTTAAGTAA
Target 3 GenBank Gene ID
Target 3 GeneCard ID SERPINC1 Link Image
Target 3 GenAtlas ID SERPINC1 Link Image
Target 3 HGNC ID HGNC:775 Link Image
Target 3 Chromosome Location 1
Target 3 Locus 1q23-q25.1
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Bayston TA, Tripodi A, Mannucci PM, Thompson E, Ireland H, Fitches AC, Hananeia L, Olds RJ, Lane DA: Familial overexpression of beta antithrombin caused by an Asn135Thr substitution. Blood. 1999 Jun 15;93(12):4242-7. [PubMed Link Image]
  2. Niiya K, Kiguchi T, Dansako H, Fujimura K, Fujimoto T, Iijima K, Tanimoto M, Harada M: Two novel gene mutations in type I antithrombin deficiency. Int J Hematol. 2001 Dec;74(4):469-72. [PubMed Link Image]
  3. Blajchman MA, Fernandez-Rachubinski F, Sheffield WP, Austin RC, Schulman S: Antithrombin-III-Stockholm: a codon 392 (Gly----Asp) mutation with normal heparin binding and impaired serine protease reactivity. Blood. 1992 Mar 15;79(6):1428-34. [PubMed Link Image]
  4. Olds RJ, Lane DA, Boisclair M, Sas G, Bock SC, Thein SL: Antithrombin Budapest 3. An antithrombin variant with reduced heparin affinity resulting from the substitution L99F. FEBS Lett. 1992 Apr 6;300(3):241-6. [PubMed Link Image]
  5. Perry DJ, Daly M, Harper PL, Tait RC, Price J, Walker ID, Carrell RW: Antithrombin Cambridge II, 384 Ala to Ser. Further evidence of the role of the reactive centre loop in the inhibitory function of the serpins. FEBS Lett. 1991 Jul 22;285(2):248-50. [PubMed Link Image]
  6. Daly M, Bruce D, Perry DJ, Price J, Harper PL, O'Meara A, Carrell RW: Antithrombin Dublin (-3 Val----Glu): an N-terminal variant which has an aberrant signal peptidase cleavage site. FEBS Lett. 1990 Oct 29;273(1-2):87-90. [PubMed Link Image]
  7. Austin RC, Rachubinski RA, Blajchman MA: Site-directed mutagenesis of alanine-382 of human antithrombin III. FEBS Lett. 1991 Mar 25;280(2):254-8. [PubMed Link Image]
  8. Mourey L, Samama JP, Delarue M, Choay J, Lormeau JC, Petitou M, Moras D: Antithrombin III: structural and functional aspects. Biochimie. 1990 Aug;72(8):599-608. [PubMed Link Image]
  9. Gandrille S, Aiach M, Lane DA, Vidaud D, Molho-Sabatier P, Caso R, de Moerloose P, Fiessinger JN, Clauser E: Important role of arginine 129 in heparin-binding site of antithrombin III. Identification of a novel mutation arginine 129 to glutamine. J Biol Chem. 1990 Nov 5;265(31):18997-9001. [PubMed Link Image]
  10. Borg JY, Brennan SO, Carrell RW, George P, Perry DJ, Shaw J: Antithrombin Rouen-IV 24 Arg----Cys. The amino-terminal contribution to heparin binding. FEBS Lett. 1990 Jun 18;266(1-2):163-6. [PubMed Link Image]
  11. 2781509 Erdjument H, Lane DA, Panico M, Di Marzo V, Morris HR, Bauer K, Rosenberg RD: Antithrombin Chicago, amino acid substitution of arginine 393 to histidine. Thromb Res. 1989 Jun 15;54(6):613-9.
  12. 3080419 Chang JY, Tran TH: Antithrombin III Basel. Identification of a Pro-Leu substitution in a hereditary abnormal antithrombin with impaired heparin cofactor activity. J Biol Chem. 1986 Jan 25;261(3):1174-6.
  13. 3162733 Erdjument H, Lane DA, Panico M, Di Marzo V, Morris HR: Single amino acid substitutions in the reactive site of antithrombin leading to thrombosis. Congenital substitution of arginine 393 to cysteine in antithrombin Northwick Park and to histidine in antithrombin Glasgow. J Biol Chem. 1988 Apr 25;263(12):5589-93.
  14. 3179438 Devraj-Kizuk R, Chui DH, Prochownik EV, Carter CJ, Ofosu FA, Blajchman MA: Antithrombin-III-Hamilton: a gene with a point mutation (guanine to adenine) in codon 382 causing impaired serine protease reactivity. Blood. 1988 Nov;72(5):1518-23.
  15. 3191114 Bock SC, Marrinan JA, Radziejewska E: Antithrombin III Utah: proline-407 to leucine mutation in a highly conserved region near the inhibitor reactive site. Biochemistry. 1988 Aug 9;27(16):6171-8.
  16. 3805013 Stephens AW, Thalley BS, Hirs CH: Antithrombin-III Denver, a reactive site variant. J Biol Chem. 1987 Jan 25;262(3):1044-8.
  17. 6298709 Bock SC, Wion KL, Vehar GA, Lawn RM: Cloning and expression of the cDNA for human antithrombin III. Nucleic Acids Res. 1982 Dec 20;10(24):8113-25.
  18. 6305982 Prochownik EV, Markham AF, Orkin SH: Isolation of a cDNA clone for human antithrombin III. J Biol Chem. 1983 Jul 10;258(13):8389-94.
  19. 6572945 Chandra T, Stackhouse R, Kidd VJ, Woo SL: Isolation and sequence characterization of a cDNA clone of human antithrombin III. Proc Natl Acad Sci U S A. 1983 Apr;80(7):1845-8.
  20. 6582486 Koide T, Odani S, Takahashi K, Ono T, Sakuragawa N: Antithrombin III Toyama: replacement of arginine-47 by cysteine in hereditary abnormal antithrombin III that lacks heparin-binding ability. Proc Natl Acad Sci U S A. 1984 Jan;81(2):289-93.
  21. 6693405 Blackburn MN, Smith RL, Carson J, Sibley CC: The heparin-binding site of antithrombin III. Identification of a critical tryptophan in the amino acid sequence. J Biol Chem. 1984 Jan 25;259(2):939-41.
  22. 7238875 Bjork I, Danielsson A, Fenton JW, Jornvall: The site in human antithrombin for functional proteolytic cleavage by human thrombin. FEBS Lett. 1981 Apr 20;126(2):257-60.
  23. 7656006 Schreuder HA, de Boer B, Dijkema R, Mulders J, Theunissen HJ, Grootenhuis PD, Hol WG: The intact and cleaved human antithrombin III complex as a model for serpin-proteinase interactions. Nat Struct Biol. 1994 Jan;1(1):48-54.
  24. 7749926 Stein PE, Carrell RW: What do dysfunctional serpins tell us about molecular mobility and disease? Nat Struct Biol. 1995 Feb;2(2):96-113.
  25. 7832187 Okajima K, Abe H, Wagatsuma M, Okabe H, Takatsuki K: Antithrombin III Kumamoto II; a single mutation at Arg393-His increased the affinity of antithrombin III for heparin. Am J Hematol. 1995 Jan;48(1):12-8.
  26. 7878627 Emmerich J, Chadeuf G, Alhenc-Gelas M, Gouault-Heilman M, Toulon P, Fiessinger JN, Aiach M: Molecular basis of antithrombin type I deficiency: the first large in-frame deletion and two novel mutations in exon 6. Thromb Haemost. 1994 Oct;72(4):534-9.
  27. 7959685 Millar DS, Wacey AI, Ribando J, Melissari E, Laursen B, Woods P, Kakkar VV, Cooper DN: Three novel missense mutations in the antithrombin III (AT3) gene causing recurrent venous thrombosis. Hum Genet. 1994 Nov;94(5):509-12.
  28. 7989582 Bruce D, Perry DJ, Borg JY, Carrell RW, Wardell MR: Thromboembolic disease due to thermolabile conformational changes of antithrombin Rouen-VI (187 Asn-->Asp) J Clin Invest. 1994 Dec;94(6):2265-74.
  29. 7994035 van Boven HH, Olds RJ, Thein SL, Reitsma PH, Lane DA, Briet E, Vandenbroucke JP, Rosendaal FR: Hereditary antithrombin deficiency: heterogeneity of the molecular basis and mortality in Dutch families. Blood. 1994 Dec 15;84(12):4209-13.
  30. 8087553 Carrell RW, Stein PE, Fermi G, Wardell MR: Biological implications of a 3 A structure of dimeric antithrombin. Structure. 1994 Apr 15;2(4):257-70.
  31. 8236149 Lane DA, Olds RJ, Boisclair M, Chowdhury V, Thein SL, Cooper DN, Blajchman M, Perry D, Emmerich J, Aiach M: Antithrombin III mutation database: first update. For the Thrombin and its Inhibitors Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost. 1993 Aug 2;70(2):361-9.
  32. 8274732 Jochmans K, Lissens W, Vervoort R, Peeters S, De Waele M, Liebaers I: Antithrombin-Gly 424 Arg: a novel point mutation responsible for type 1 antithrombin deficiency and neonatal thrombosis. Blood. 1994 Jan 1;83(1):146-51.
  33. 8443391 Okajima K, Abe H, Maeda S, Motomura M, Tsujihata M, Nagataki S, Okabe H, Takatsuki K: Antithrombin III Nagasaki (Ser116-Pro): a heterozygous variant with defective heparin binding associated with thrombosis. Blood. 1993 Mar 1;81(5):1300-5.
  34. 8476848 Olds RJ, Lane DA, Chowdhury V, De Stefano V, Leone G, Thein SL: Complete nucleotide sequence of the antithrombin gene: evidence for homologous recombination causing thrombophilia. Biochemistry. 1993 Apr 27;32(16):4216-24.
  35. 8486379 Olds RJ, Lane DA, Beresford CH, Abildgaard U, Hughes PM, Thein SL: A recurrent deletion in the antithrombin gene, AT106-108(-6 bp), identified by DNA heteroduplex detection. Genomics. 1993 Apr;16(1):298-9.
  36. 8664906 Perry DJ, Carrell RW: Molecular genetics of human antithrombin deficiency. Hum Mutat. 1996;7(1):7-22.
  37. 9067613 Skinner R, Abrahams JP, Whisstock JC, Lesk AM, Carrell RW, Wardell MR: The 2.6 A structure of antithrombin indicates a conformational change at the heparin binding site. J Mol Biol. 1997 Feb 28;266(3):601-9.
  38. 9761669 Skinner R, Chang WS, Jin L, Pei X, Huntington JA, Abrahams JP, Carrell RW, Lomas DA: Implications for function and therapy of a 2.9 A structure of binary-complexed antithrombin. J Mol Biol. 1998;283(1):9-14.
  39. 9845533 Fitches AC, Appleby R, Lane DA, De Stefano V, Leone G, Olds RJ: Impaired cotranslational processing as a mechanism for type I antithrombin deficiency. Blood. 1998 Dec 15;92(12):4671-6.
Target 3 Drug References
  1. Kaiserman D, Whisstock JC, Bird PI: Mechanisms of serpin dysfunction in disease. Expert Rev Mol Med. 2006 Dec 11;8(31):1-19. [PubMed Link Image]
  2. Pappalardo F, Franco A, Crescenzi G, De Simone F, Torracca L, Zangrillo A: Anticoagulation management in patients undergoing open heart surgery by activated clotting time and whole blood heparin concentration. Perfusion. 2006 Dec;21(5):285-90. [PubMed Link Image]
  3. Lee S, Gibson CM: Enoxaparin in acute coronary syndromes. Expert Rev Cardiovasc Ther. 2007 May;5(3):387-99. [PubMed Link Image]
  4. Mirow N, Zimmermann B, Maleszka A, Knobl H, Tenderich G, Koerfer R, Herberg FW: Plasma protein binding properties to immobilized heparin and heparin-albumin conjugate. Artif Organs. 2007 Jun;31(6):466-71. [PubMed Link Image]
  5. Sun W, Bandmann H, Schrader T: A Fluorescent Polymeric Heparin Sensor. Chemistry. 2007 Sep 17;13(27):7701-7707. [PubMed Link Image]
Drug Target 4 [top]
Target 4 ID 400
Target 4 Name Coagulation factor IX
Target 4 Synonyms
  1. Christmas factor
  2. Coagulation factor IX precursor
  3. EC 3.4.21.22
  4. PTC
  5. Plasma thromboplastin component
Target 4 Gene Name F9
Target 4 Protein Sequence >Coagulation factor IX precursor 
MQRVNMIMAESPGLITICLLGYLLSAECTVFLDHENANKILNRPKRYNSGKLEEFVQGNL
ERECMEEKCSFEEAREVFENTERTTEFWKQYVDGDQCESNPCLNGGSCKDDINSYECWCP
FGFEGKNCELDVTCNIKNGRCEQFCKNSADNKVVCSCTEGYRLAENQKSCEPAVPFPCGR
VSVSQTSKLTRAETVFPDVDYVNSTEAETILDNITQSTQSFNDFTRVVGGEDAKPGQFPW
QVVLNGKVDAFCGGSIVNEKWIVTAAHCVETGVKITVVAGEHNIEETEHTEQKRNVIRII
PHHNYNAAINKYNHDIALLELDEPLVLNSYVTPICIADKEYTNIFLKFGSGYVSGWGRVF
HKGRSALVLQYLRVPLVDRATCLRSTKFTIYNNMFCAGFHEGGRDSCQGDSGGPHVTEVE
GTSFLTGIISWGEECAMKGKYGIYTKVSRYVNWIKEKTKLT
Target 4 Number of Residues 468
Target 4 Molecular Weight 51779
Target 4 Theoretical pI 5.16
Target 4 GO Classification
Function
catalytic activity
hydrolase activity
peptidase activity
endopeptidase activity
serine-type endopeptidase activity
binding
ion binding
cation binding
calcium ion binding
Process
metabolism
macromolecule metabolism
protein metabolism
cellular protein metabolism
proteolysis
physiological process
organismal physiological process
regulation of body fluids
hemostasis
blood coagulation
Component
extracellular region
Target 4 General Function Involved in calcium ion binding
Target 4 Specific Function Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca(2+) ions, phospholipids, and factor VIIIa
Target 4 Pathways Not Available
Target 4 Reactions
  • Selective cleavage of Arg!Ile bond in factor X to form factor Xa
Target 4 Pfam Domain Function
Target 4 Signals
  • 1-28
Target 4 Transmembrane Regions
  • None
Target 4 Essentiality Non-Essential
Target 4 GenBank ID Protein 182609 Link Image
Target 4 UniProtKB/Swiss-Prot ID P00740 Link Image
Target 4 UniProtKB/Swiss-Prot Entry Name FA9_HUMAN Link Image
Target 4 PDB ID 1RFN Link Image
Target 4 PDB File Show
Target 4 3D Structure
Target 4 Cellular Location
  • Secreted protein
Target 4 Gene Sequence >1389 bp 
ATGCAGCGCGTGAACATGATCATGGCAGAATCACCAAGCCTCATCACCATCTGCCTTTTA
GGATATCTACTCAGTGCTGAATGTACAGTTTTTCTTGATCATGAAAACGCCAACAAAATT
CTGAATCGGCCAAAGAGGTATAATTCAGGTAAATTGGAAGAGTTTGTTCAAGGGAACCTT
GAGAGAGAATGTATGGAAGAAAAGTGTAGTTTTGAAGAACCACGAGAAGTTTTTGAAAAC
ACTGAAAAGACAACTGAATTTTGGAAGCAGTATGTTGATGGAGATCAGTGTGAGTCCAAT
CCATGTTTAAATGGCGGCAGTTGCAAGGATGACATTAATTCCTATGAATGTTGGTGTCCC
TTTGGATTTGAAGGAAAGAACTGTGAATTAGATGTAACATGTAACATTAAGAATGGCAGA
TGCGAGCAGTTTTGTAAAAATAGTGCTGATAACAAGGTGGTTTGCTCCTGTACTGAGGGA
TATCGACTTGCAGAAAACCAGAAGTCCTGTGAACCAGCAGTGCCATTTCCATGTGGAAGA
GTTTCTGTTTCACAAACTTCTAAGCTCACCCGTGCTGAGGCTGTTTTTCCTGATGTGGAC
TATGTAAATCCTACTGAAGCTGAAACCATTTTGGATAACATCACTCAAGGCACCCAATCA
TTTAATGACTTCACTCGGGTTGTTGGTGGAGAAGATGCCAAACCAGGTCAATTCCCTTGG
CAGGTTGTTTTGAATGGTAAAGTTGATGCATTCTGTGGAGGCTCTATCGTTAATGAAAAA
TGGATTGTAACTGCTGCCCACTGTGTTGAAACTGGTGTTAAAATTACAGTTGTCGCAGGT
GAACATAATATTGAGGAGACAGAACATACAGAGCAAAAGCGAAATGTGATTCGAGCAATT
ATTCCTCACCACAACTACAATGCAGCTATTAATAAGTACAACCATGACATTGCCCTTCTG
GAACTGGACGAACCCTTAGTGCTAAACAGCTACGTTACACCTATTTGCATTGCTGACAAG
GAATACACGAACATCTTCCTCAAATTTGGATCTGGCTATGTAAGTGGCTGGGCAAGAGTC
TTCCACAAAGGGAGATCAGCTTTAGTTCTTCAGTACCTTAGAGTTCCACTTGTTGACCGA
GCCACATGTCTTCGATCTACAAAGTTCACCATCTATAACAACATGTTCTGTGCTGGCTTC
CATGAAGGAGGTAGAGATTCATGTCAAGGAGATAGTGGGGGACCCCATGTTACTGAAGTG
GAAGGGACCAGTTTCTTAACTGGAATTATTAGCTGGGGTGAAGAGTGTGCAATGAAAGGC
AAATATGGAATATATACCAAGGTATCCCGGTATGTCAACTGGATTAAGGAAAAAACAAAG
CTCACTTAA
Target 4 GenBank Gene ID
Target 4 GeneCard ID F9 Link Image
Target 4 GenAtlas ID F9 Link Image
Target 4 HGNC ID HGNC:3551 Link Image
Target 4 Chromosome Location X
Target 4 Locus Xq27.1-q27.2
Target 4 SNPs SNPJam Report Link Image
Target 4 General References
  1. Montejo JM, Magallon M, Tizzano E, Solera J: Identification of twenty-one new mutations in the factor IX gene by SSCP analysis. Hum Mutat. 1999;13(2):160-5. [PubMed Link Image]
  2. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed Link Image]
  3. Hopfner KP, Lang A, Karcher A, Sichler K, Kopetzki E, Brandstetter H, Huber R, Bode W, Engh RA: Coagulation factor IXa: the relaxed conformation of Tyr99 blocks substrate binding. Structure. 1999 Aug 15;7(8):989-96. [PubMed Link Image]
  4. Wulff K, Bykowska K, Lopaciuk S, Herrmann FH: Molecular analysis of hemophilia B in Poland: 12 novel mutations of the factor IX gene. Acta Biochim Pol. 1999;46(3):721-6. [PubMed Link Image]
  5. Vidal F, Farssac E, Altisent C, Puig L, Gallardo D: Factor IX gene sequencing by a simple and sensitive 15-hour procedure for haemophilia B diagnosis: identification of two novel mutations. Br J Haematol. 2000 Nov;111(2):549-51. [PubMed Link Image]
  6. Arruda VR, Hagstrom JN, Deitch J, Heiman-Patterson T, Camire RM, Chu K, Fields PA, Herzog RW, Couto LB, Larson PJ, High KA: Posttranslational modifications of recombinant myotube-synthesized human factor IX. Blood. 2001 Jan 1;97(1):130-8. [PubMed Link Image]
  7. Onay UV, Kavakli K, Kilinc Y, Gurgey A, Aktuglu G, Kemahli S, Ozbek U, Caglayan SH: Molecular pathology of haemophilia B in Turkish patients: identification of a large deletion and 33 independent point mutations. Br J Haematol. 2003 Feb;120(4):656-9. [PubMed Link Image]
  8. Espinos C, Casana P, Haya S, Cid AR, Aznar JA: Molecular analyses in hemophilia B families: identification of six new mutations in the factor IX gene. Haematologica. 2003 Feb;88(2):235-6. [PubMed Link Image]
  9. Baron M, Norman DG, Harvey TS, Handford PA, Mayhew M, Tse AG, Brownlee GG, Campbell ID: The three-dimensional structure of the first EGF-like module of human factor IX: comparison with EGF and TGF-alpha. Protein Sci. 1992 Jan;1(1):81-90. [PubMed Link Image]
  10. Ludwig M, Sabharwal AK, Brackmann HH, Olek K, Smith KJ, Birktoft JJ, Bajaj SP: Hemophilia B caused by five different nondeletion mutations in the protease domain of factor IX. Blood. 1992 Mar 1;79(5):1225-32. [PubMed Link Image]
  11. 1517205 Nishimura H, Takao T, Hase S, Shimonishi Y, Iwanaga S: Human factor IX has a tetrasaccharide O-glycosidically linked to serine 61 through the fucose residue. J Biol Chem. 1992 Sep 5;267(25):17520-5.
  12. 1615485 Taylor SA, Duffin J, Cameron C, Teitel J, Garvey B, Lillicrap DP: Characterization of the original Christmas disease mutation (cysteine 206----serine): from clinical recognition to molecular pathogenesis. Thromb Haemost. 1992 Jan 23;67(1):63-5.
  13. 1634040 Sommer SS: Assessing the underlying pattern of human germline mutations: lessons from the factor IX gene. FASEB J. 1992 Jul;6(10):2767-74.
  14. 1854745 Huang LH, Cheng H, Pardi A, Tam JP, Sweeney WV: Sequence-specific 1H NMR assignments, secondary structure, and location of the calcium binding site in the first epidermal growth factor like domain of blood coagulation factor IX. Biochemistry. 1991 Jul 30;30(30):7402-9.
  15. 1902289 Sarkar G, Cassady JD, Pyeritz RE, Gilchrist GS, Sommer SS: Isoleucine397 is changed to threonine in two females with hemophilia B. Nucleic Acids Res. 1991 Mar 11;19(5):1165.
  16. 1958666 Miyata T, Sakai T, Sugimoto M, Naka H, Yamamoto K, Yoshioka A, Fukui H, Mitsui K, Kamiya K, Umeyama H, et al.: Factor IX Amagasaki: a new mutation in the catalytic domain resulting in the loss of both coagulant and esterase activities. Biochemistry. 1991 Nov 26;30(47):11286-91.
  17. 2129367 Iwanaga S, Nishimura H, Kawabata S, Kisiel W, Hase S, Ikenaka T: A new trisaccharide sugar chain linked to a serine residue in the first EGF-like domain of clotting factors VII and IX and protein Z. Adv Exp Med Biol. 1990;281:121-31.
  18. 2162822 Bertina RM, van der Linden IK, Mannucci PM, Reinalda-Poot HH, Cupers R, Poort SR, Reitsma PH: Mutations in hemophilia Bm occur at the Arg180-Val activation site or in the catalytic domain of factor IX. J Biol Chem. 1990 Jul 5;265(19):10876-83.
  19. 2339358 Wang NS, Zhang M, Thompson AR, Chen SH: Factor IX Chongqing: a new mutation in the calcium-binding domain of factor IX resulting in severe hemophilia B. Thromb Haemost. 1990 Feb 19;63(1):24-6.
  20. 2372509 Taylor SA, Liddell MB, Peake IR, Bloom AL, Lillicrap DP: A mutation adjacent to the beta cleavage site of factor IX (valine 182 to leucine) results in mild haemophilia Bm. Br J Haematol. 1990 Jun;75(2):217-21.
  21. 2472424 Chen SH, Thompson AR, Zhang M, Scott CR: Three point mutations in the factor IX genes of five hemophilia B patients. Identification strategy using localization by altered epitopes in their hemophilic proteins. J Clin Invest. 1989 Jul;84(1):113-8.
  22. 2511201 Nishimura H, Kawabata S, Kisiel W, Hase S, Ikenaka T, Takao T, Shimonishi Y, Iwanaga S: Identification of a disaccharide (Xyl-Glc) and a trisaccharide (Xyl2-Glc) O-glycosidically linked to a serine residue in the first epidermal growth factor-like domain of human factors VII and IX and protein Z and bovine protein Z. J Biol Chem. 1989 Dec 5;264(34):20320-5.
  23. 2592373 Suehiro K, Kawabata S, Miyata T, Takeya H, Takamatsu J, Ogata K, Kamiya T, Saito H, Niho Y, Iwanaga S: Blood clotting factor IX BM Nagoya. Substitution of arginine 180 by tryptophan and its activation by alpha-chymotrypsin and rat mast cell chymase. J Biol Chem. 1989 Dec 15;264(35):21257-65.
  24. 2713493 Monroe DM, McCord DM, Huang MN, High KA, Lundblad RL, Kasper CK, Roberts HR: Functional consequences of an arginine180 to glutamine mutation in factor IX Hilo. Blood. 1989 May 1;73(6):1540-4.
  25. 2714791 Attree O, Vidaud D, Vidaud M, Amselem S, Lavergne JM, Goossens M: Mutations in the catalytic domain of human coagulation factor IX: rapid characterization by direct genomic sequencing of DNA fragments displaying an altered melting behavior. Genomics. 1989 Apr;4(3):266-72.
  26. 2738071 Ware J, Diuguid DL, Liebman HA, Rabiet MJ, Kasper CK, Furie BC, Furie B, Stafford DW: Factor IX San Dimas. Substitution of glutamine for Arg-4 in the propeptide leads to incomplete gamma-carboxylation and altered phospholipid binding properties. J Biol Chem. 1989 Jul 5;264(19):11401-6.
  27. 2743975 Green PM, Bentley DR, Mibashan RS, Nilsson IM, Giannelli F: Molecular pathology of haemophilia B. EMBO J. 1989 Apr;8(4):1067-72.
  28. 2753873 Sakai T, Yoshioka A, Yamamoto K, Niinomi K, Fujimura Y, Fukui H, Miyata T, Iwanaga S: Blood clotting factor IX Kashihara: amino acid substitution of valine-182 by phenylalanine. J Biochem (Tokyo). 1989 May;105(5):756-9.
  29. 2773937 Koeberl DD, Bottema CD, Buerstedde JM, Sommer SS: Functionally important regions of the factor IX gene have a low rate of polymorphism and a high rate of mutation in the dinucleotide CpG. Am J Hum Genet. 1989 Sep;45(3):448-57.
  30. 2775660 Liddell MB, Peake IR, Taylor SA, Lillicrap DP, Giddings JC, Bloom AL: Factor IX Cardiff: a variant factor IX protein that shows abnormal activation is caused by an arginine to cysteine substitution at position 145. Br J Haematol. 1989 Aug;72(4):556-60.
  31. 2994716 Yoshitake S, Schach BG, Foster DC, Davie EW, Kurachi K: Nucleotide sequence of the gene for human factor IX (antihemophilic factor B). Biochemistry. 1985 Jul 2;24(14):3736-50.
  32. 3009023 Bentley AK, Rees DJ, Rizza C, Brownlee GG: Defective propeptide processing of blood clotting factor IX caused by mutation of arginine to glutamine at position -4. Cell. 1986 May 9;45(3):343-8.
  33. 3243764 Sugimoto M, Miyata T, Kawabata S, Yoshioka A, Fukui H, Takahashi H, Iwanaga S: Blood clotting factor IX Niigata: substitution of alanine-390 by valine in the catalytic domain. J Biochem (Tokyo). 1988 Dec;104(6):878-80.
  34. 3340835 Stoflet ES, Koeberl DD, Sarkar G, Sommer SS: Genomic amplification with transcript sequencing. Science. 1988 Jan 29;239(4839):491-4.
  35. 3401602 Ware J, Davis L, Frazier D, Bajaj SP, Stafford DW: Genetic defect responsible for the dysfunctional protein: factor IXLong Beach. Blood. 1988 Aug;72(2):820-2.
  36. 3790720 Davis LM, McGraw RA, Ware JL, Roberts HR, Stafford DW: Factor IXAlabama: a point mutation in a clotting protein results in hemophilia B. Blood. 1987 Jan;69(1):140-3.
  37. 3857619 McGraw RA, Davis LM, Noyes CM, Lundblad RL, Roberts HR, Graham JB, Stafford DW: Evidence for a prevalent dimorphism in the activation peptide of human coagulation factor IX. Proc Natl Acad Sci U S A. 1985 May;82(9):2847-51.
  38. 6089357 Jagadeeswaran P, Lavelle DE, Kaul R, Mohandas T, Warren ST: Isolation and characterization of human factor IX cDNA: identification of Taq I polymorphism and regional assignment. Somat Cell Mol Genet. 1984 Sep;10(5):465-73.
  39. 6329734 Anson DS, Choo KH, Rees DJ, Giannelli F, Gould K, Huddleston JA, Brownlee GG: The gene structure of human anti-haemophilic factor IX. EMBO J. 1984 May;3(5):1053-60.
  40. 6425296 Morita T, Isaacs BS, Esmon CT, Johnson AE: Derivatives of blood coagulation factor IX contain a high affinity Ca2+-binding site that lacks gamma-carboxyglutamic acid. J Biol Chem. 1984 May 10;259(9):5698-704.
  41. 659613 Di Scipio RG, Kurachi K, Davie EW: Activation of human factor IX (Christmas factor). J Clin Invest. 1978 Jun;61(6):1528-38.
  42. 6603618 Noyes CM, Griffith MJ, Roberts HR, Lundblad RL: Identification of the molecular defect in factor IX Chapel Hill: substitution of histidine for arginine at position 145. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4200-2.
  43. 6687940 Jaye M, de la Salle H, Schamber F, Balland A, Kohli V, Findeli A, Tolstoshev P, Lecocq JP: Isolation of a human anti-haemophilic factor IX cDNA clone using a unique 52-base synthetic oligonucleotide probe deduced from the amino acid sequence of bovine factor IX. Nucleic Acids Res. 1983 Apr 25;11(8):2325-35.
  44. 6688526 McMullen BA, Fujikawa K, Kisiel W: The occurrence of beta-hydroxyaspartic acid in the vitamin K-dependent blood coagulation zymogens. Biochem Biophys Res Commun. 1983 Aug 30;115(1):8-14.
  45. 7547952 Freedman SJ, Furie BC, Furie B, Baleja JD: Structure of the calcium ion-bound gamma-carboxyglutamic acid-rich domain of factor IX. Biochemistry. 1995 Sep 26;34(38):12126-37.
  46. 7606779 Rao Z, Handford P, Mayhew M, Knott V, Brownlee GG, Stuart D: The structure of a Ca(2+)-binding epidermal growth factor-like domain: its role in protein-protein interactions. Cell. 1995 Jul 14;82(1):131-41.
  47. 7713897 Freedman SJ, Furie BC, Furie B, Baleja JD: Structure of the metal-free gamma-carboxyglutamic acid-rich membrane binding region of factor IX by two-dimensional NMR spectroscopy. J Biol Chem. 1995 Apr 7;270(14):7980-7.
  48. 7981722 Caglayan SH, Vielhaber E, Gursel T, Aktuglu G, Sommer SS: Identification of mutations in four hemophilia B patients of Turkish origin, including a novel deletion of base 6411. Hum Mutat. 1994;4(2):163-5.
  49. 8076946 Aguilar-Martinez P, Romey MC, Schved JF, Gris JC, Demaille J, Claustres M: Factor IX gene mutations causing haemophilia B: comparison of SSC screening versus systematic DNA sequencing and diagnostic applications. Hum Genet. 1994 Sep;94(3):287-90.
  50. 8199596 Aguilar-Martinez P, Romey MC, Gris JC, Schved JF, Demaille J, Claustres M: A novel mutation (Val-373 to Glu) in the catalytic domain of factor IX, resulting in moderately/severe hemophilia B in a southern French patient. Hum Mutat. 1994;3(2):156-8.
  51. 8236150 de la Salle C, Charmantier JL, Baas MJ, Schwartz A, Wiesel ML, Grunebaum L, Cazenave JP: A deletion located in the 3' non translated part of the factor IX gene responsible for mild haemophilia B. Thromb Haemost. 1993 Aug 2;70(2):370-1.
  52. 8257988 David D, Rosa HA, Pemberton S, Diniz MJ, Campos M, Lavinha J: Single-strand conformation polymorphism (SSCP) analysis of the molecular pathology of hemophilia B. Hum Mutat. 1993;2(5):355-61.
  53. 8295821 de la Salle C, Charmantier JL, Ravanat C, Ohlmann P, Hartmann ML, Schuhler S, Bischoff R, Ebel C, Roecklin D, Balland A, et al.: The Arg-4 mutant factor IX Strasbourg 2 shows a delayed activation by factor XIa. Nouv Rev Fr Hematol. 1993;35(5):473-80.
  54. 8392713 Giannelli F, Green PM, High KA, Sommer S, Poon MC, Ludwig M, Schwaab R, Reitsma PH, Goossens M, Yoshioka A, et al.: Haemophilia B: database of point mutations and short additions and deletions--fourth edition, 1993. Nucleic Acids Res. 1993 Jul 1;21(13):3075-87.
  55. 8663165 Freedman SJ, Blostein MD, Baleja JD, Jacobs M, Furie BC, Furie B: Identification of the phospholipid binding site in the vitamin K-dependent blood coagulation protein factor IX. J Biol Chem. 1996 Jul 5;271(27):16227-36.
  56. 8680410 Wulff K, Schroder W, Wehnert M, Herrmann FH: Twenty-five novel mutations of the factor IX gene in haemophilia B. Hum Mutat. 1995;6(4):346-8.
  57. 8833911 Chu K, Wu SM, Stanley T, Stafford DW, High KA: A mutation in the propeptide of Factor IX leads to warfarin sensitivity by a novel mechanism. J Clin Invest. 1996 Oct 1;98(7):1619-25.
  58. 9047312 Li L, Darden TA, Freedman SJ, Furie BC, Furie B, Baleja JD, Smith H, Hiskey RG, Pedersen LG: Refinement of the NMR solution structure of the gamma-carboxyglutamic acid domain of coagulation factor IX using molecular dynamics simulation with initial Ca2+ positions determined by a genetic algorithm. Biochemistry. 1997 Feb 25;36(8):2132-8.
  59. 9222764 Caglayan SH, Gokmen Y, Aktuglu G, Gurgey A, Sommer SS: Mutations associated with hemophilia B in Turkish patients. Hum Mutat. 1997;10(1):76-9.
  60. 9452115 David D, Moreira I, Morais S, de Deus G: Five novel factor IX mutations in unrelated hemophilia B patients. Hum Mutat. 1998;Suppl 1:S301-3.
  61. 9590153 Chan V, Chan VW, Yip B, Chim CS, Chan TK: Hemophilia B in a female carrier due to skewed inactivation of the normal X-chromosome. Am J Hematol. 1998 May;58(1):72-6.
  62. 9600455 Heit JA, Thorland EC, Ketterling RP, Lind TJ, Daniels TM, Zapata RE, Ordonez SM, Kasper CK, Sommer SS: Germline mutations in Peruvian patients with hemophilia B: pattern of mutation in AmerIndians is similar to the putative endogenous germline pattern. Hum Mutat. 1998;11(5):372-6.
Target 4 Drug References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
Drug Target 5 [top]
Target 5 ID 1719
Target 5 Name Heparanase
Target 5 Synonyms
  1. EC 3.2.-.-
  2. Endo- glucoronidase
  3. Heparanase precursor
  4. Heparanase-1
  5. Hpa1
Target 5 Gene Name HPSE
Target 5 Protein Sequence >Heparanase precursor 
MLLRSKPALPPPLMLLLLGPLGPLSPGALPRPAQAQDVVDLDFFTQEPLHLVSPSFLSVT
IDANLATDPRFLILLGSPKLRTLARGLSPAYLRFGGTKTDFLIFDPKKESTFEERSYWQS
QVNQDICKYGSIPPDVEEKLRLEWPYQEQLLLREHYQKKFKNSTYSRSSVDVLYTFANCS
GLDLIFGLNALLRTADLQWNSSNAQLLLDYCSSKGYNISWELGNEPNSFLKKADIFINGS
QLGEDFIQLHKLLRKSTFKNAKLYGPDVGQPRRKTAKMLKSFLKAGGEVIDSVTWHHYYL
NGRTATREDFLNPDVLDIFISSVQKVFQVVESTRPGKKVWLGETSSAYGGGAPLLSDTFA
AGFMWLDKLGLSARMGIEVVMRQVFFGAGNYHLVDENFDPLPDYWLSLLFKKLVGTKVLM
ASVQGSKRRKLRVYLHCTNTDNPRYKEGDLTLYAINLHNVTKYLRLPYPFSNKQVDKYLL
RPLGPHGLLSKSVQLNGLTLKMVDDQTLPPLMEKPLRPGSSLGLPAFSYSFFVIRNAKVA
ACI
Target 5 Number of Residues 552
Target 5 Molecular Weight 61177
Target 5 Theoretical pI 9.72
Target 5 GO Classification Not Available
Target 5 General Function Involved in beta-glucuronidase activity
Target 5 Specific Function Endoglycosidase which is a cell surface and extracellular matrix-degrading enzyme. Cleaves heparan sulfate proteoglycans (HSPGs) into heparan sulfate side chains and core proteoglycans. Also implicated in the extravasation of leukocytes and tumor cell lines. Due to its contribution to metastasis and angiogenesis, it is considered to be a potential target for anti- cancer therapies
Target 5 Pathways Not Available
Target 5 Reactions Not Available
Target 5 Pfam Domain Function
Target 5 Signals
  • 1-35
Target 5 Transmembrane Regions
  • None
Target 5 Essentiality Non-Essential
Target 5 GenBank ID Protein 5616197 Link Image
Target 5 UniProtKB/Swiss-Prot ID Q9Y251 Link Image
Target 5 UniProtKB/Swiss-Prot Entry Name HPSE_HUMAN Link Image
Target 5 PDB ID Not Available
Target 5 Cellular Location
  • Lysosome
  • lysosomal membrane
  • peripheral membrane protein. Secreted protein. Note=Secreted, internal
Target 5 Gene Sequence >1632 bp 
ATGCTGCTGCGCTCGAAGCCTGCGCTGCCGCCGCCGCTGATGCTGCTGCTCCTGGGGCCG
CTGGGTCCCCTCTCCCCTGGCGCCCTGCCCCGACCTGCGCAAGCACAGGACGTCGTGGAC
CTGGACTTCTTCACCCAGGAGCCGCTGCACCTGGTGAGCCCCTCGTTCCTGTCCGTCACC
ATTGACGCCAACCTGGCCACGGACCCGCGGTTCCTCATCCTCCTGGGTTCTCCAAAGCTT
CGTACCTTGGCCAGAGGCTTGTCTCCTGCGTACCTGAGGTTTGGTGGCACCAAGACAGAC
TTCCTAATTTTCGATCCCAAGAAGGAATCAACCTTTGAAGAGAGAAGTTACTGGCAATCT
CAAGTCAACCAGGATATTTGCAAATATGGATCCATCCCTCCTGATGTGGAGGAGAAGTTA
CGGTTGGAATGGCCCTACCAGGAGCAATTGCTACTCCGAGAACACTACCAGAAAAAGTTC
AAGAACAGCACCTACTCAAGAAGCTCTGTAGATGTGCTATACACTTTTGCAAACTGCTCA
GGACTGGACTTGATCTTTGGCCTAAATGCGTTATTAAGAACAGCAGATTTGCAGTGGAAC
AGTTCTAATGCTCAGTTGCTCCTGGACTACTGCTCTTCCAAGGGGTATAACATTTCTTGG
GAACTAGGCAATGAACCTAACAGTTTCCTTAAGAAGGCTGATATTTTCATCAATGGGTCG
CAGTTAGGAGAAGATTTTATTCAATTGCATAAACTTCTAAGAAAGTCCACCTTCAAAAAT
GCAAAACTCTATGGTCCTGATGTTGGTCAGCCTCGAAGAAAGACGGCTAAGATGCTGAAG
AGCTTCCTGAAGGCTGGTGGAGAAGTGATTGATTCAGTTACATGGCATCACTACTATTTG
AATGGACGGACTGCTACCAGGGAAGATTTTCTAAACCCTGATGTATTGGACATTTTTATT
TCATCTGTGCAAAAAGTTTTCCAGGTGGTTGAGAGCACCAGGCCTGGCAAGAAGGTCTGG
TTAGGAGAAACAAGCTCTGCATATGGAGGCGGAGCGCCCTTGCTATCCGACACCTTTGCA
GCTGGCTTTATGTGGCTGGATAAATTGGGCCTGTCAGCCCGAATGGGAATAGAAGTGGTG
ATGAGGCAAGTATTCTTTGGAGCAGGAAACTACCATTTAGTGGATGAAAACTTCGATCCT
TTACCTGATTATTGGCTATCTCTTCTGTTCAAGAAATTGGTGGGCACCAAGGTGTTAATG
GCAAGCGTGCAAGGTTCAAAGAGAAGGAAGCTTCGAGTATACCTTCATTGCACAAACACT
GACAATCCAAGGTATAAAGAAGGAGATTTAACTCTGTATGCCATAAACCTCCATAATGTC
ACCAAGTACTTGCGGTTACCCTATCCTTTTTCTAACAAGCAAGTGGATAAATACCTTCTA
AGACCTTTGGGACCTCATGGATTACTTTCCAAATCTGTCCAACTCAATGGTCTAACTCTA
AAGATGGTGGATGATCAAACCTTGCCACCTTTAATGGAAAAACCTCTCCGGCCAGGAAGT
TCACTGGGCTTGCCAGCTTTCTCATATAGTTTTTTTGTGATAAGAAATGCCAAAGTTGCT
GCTTGCATCTGA
Target 5 GenBank Gene ID
Target 5 GeneCard ID HPSE Link Image
Target 5 GenAtlas ID HPSE Link Image
Target 5 HGNC ID HGNC:5164 Link Image
Target 5 Chromosome Location 4
Target 5 Locus 4q21.3
Target 5 SNPs SNPJam Report Link Image
Target 5 General References
  1. Hulett MD, Freeman C, Hamdorf BJ, Baker RT, Harris MJ, Parish CR: Cloning of mammalian heparanase, an important enzyme in tumor invasion and metastasis. Nat Med. 1999 Jul;5(7):803-9. [PubMed Link Image]
  2. Kussie PH, Hulmes JD, Ludwig DL, Patel S, Navarro EC, Seddon AP, Giorgio NA, Bohlen P: Cloning and functional expression of a human heparanase gene. Biochem Biophys Res Commun. 1999 Jul 22;261(1):183-7. [PubMed Link Image]
  3. Toyoshima M, Nakajima M: Human heparanase. Purification, characterization, cloning, and expression. J Biol Chem. 1999 Aug 20;274(34):24153-60. [PubMed Link Image]
  4. Dempsey LA, Plummer TB, Coombes SL, Platt JL: Heparanase expression in invasive trophoblasts and acute vascular damage. Glycobiology. 2000 May;10(5):467-75. [PubMed Link Image]
Target 5 Drug References
  1. Zhao H, Liu H, Chen Y, Xin X, Li J, Hou Y, Zhang Z, Zhang X, Xie C, Geng M, Ding J: Oligomannurarate Sulfate, a Novel Heparanase Inhibitor Simultaneously Targeting Basic Fibroblast Growth Factor, Combats Tumor Angiogenesis and Metastasis. Cancer Res. 2006 Sep 1;66(17):8779-8787. [PubMed Link Image]
  2. Waterman M, Ben-Izhak O, Eliakim R, Groisman G, Vlodavsky I, Ilan N: Heparanase upregulation by colonic epithelium in inflammatory bowel disease. Mod Pathol. 2007 Jan;20(1):8-14. Epub 2006 Oct 13. [PubMed Link Image]
  3. Hostettler N, Naggi A, Torri G, Ishai-Michaeli R, Casu B, Vlodavsky I, Borsig L: P-selectin- and heparanase-dependent antimetastatic activity of non-anticoagulant heparins. FASEB J. 2007 Jun 8;. [PubMed Link Image]
  4. Han J, Woytowich AE, Mandal AK, Hiebert LM: Heparanase upregulation in high glucose-treated endothelial cells is prevented by insulin and heparin. Exp Biol Med (Maywood). 2007 Jul;232(7):927-34. [PubMed Link Image]
  5. Bisio A, Mantegazza A, Urso E, Naggi A, Torri G, Viskov C, Casu B: High-performance liquid chromatographic/mass spectrometric studies on the susceptibility of heparin species to cleavage by heparanase. Semin Thromb Hemost. 2007 Jul;33(5):488-95. [PubMed Link Image]
Drug Target 6 [top]
Target 6 ID 2058
Target 6 Name P-selectin
Target 6 Synonyms
  1. CD62P antigen
  2. GMP-140
  3. Granule membrane protein 140
  4. LECAM3
  5. Leukocyte-endothelial cell adhesion molecule 3
  6. P-selectin precursor
  7. PADGEM
Target 6 Gene Name SELP
Target 6 Protein Sequence >P-selectin precursor 
MANCQIAILYQRFQRVVFGISQLLCFSALISELTNQKEVAAWTYHYSTKAYSWNISRKYC
QNRYTDLVAIQNKNEIDYLNKVLPYYSSYYWIGIRKNNKTWTWVGTKKALTNEAENWADN
EPNNKRNNEDCVEIYIKSPSAPGKWNDEHCLKKKHALCYTASCQDMSCSKQGECLETIGN
YTCSCYPGFYGPECEYVRECGELELPQHVLMNCSHPLGNFSFNSQCSFHCTDGYQVNGPS
KLECLASGIWTNKPPQCLAAQCPPLKIPERGNMICLHSAKAFQHQSSCSFSCEEGFALVG
PEVVQCTASGVWTAPAPVCKAVQCQHLEAPSEGTMDCVHPLTAFAYGSSCKFECQPGYRV
RGLDMLRCIDSGHWSAPLPTCEAISCEPLESPVHGSMDCSPSLRAFQYDTNCSFRCAEGF
MLRGADIVRCDNLGQWTAPAPVCQALQCQDLPVPNEARVNCSHPFGAFRYQSVCSFTCNE
GLLLVGASVLQCLATGNWNSVPPECQAIPCTPLLSPQNGTMTCVQPLGSSSYKSTCQFIC
DEGYSLSGPERLDCTRSGRWTDSPPMCEAIKCPELFAPEQGSLDCSDTRGEFNVGSTCHF
SCNNGFKLEGPNNVECTTSGRWSATPPTCKGIASLPTPGLQCPALTTPGQGTMYCRHHPG
TFGFNTTCYFGCNAGFTLIGDSTLSCRPSGQWTAVTPACRAVKCSELHVNKPIAMNCSNL
WGNFSYGSICSFHCLEGQLLNGSAQTACQENGHWSTTVPTCQAGPLTIQEALTYFGGAVA
STIGLIMGGTLLALLRKRFRQKDDGKCPLNPHSHLGTYGVFTNAAFDPSP
Target 6 Number of Residues 843
Target 6 Molecular Weight 90845
Target 6 Theoretical pI 6.64
Target 6 GO Classification
Function
binding
carbohydrate binding
sugar binding
Process
cellular process
cell adhesion
Component
cell
membrane
Target 6 General Function Involved in sugar binding
Target 6 Specific Function Ca(2+)-dependent receptor for myeloid cells that binds to carbohydrates on neutrophils and monocytes. Mediates the interaction of activated endothelial cells or platelets with leukocytes. The ligand recognized is sialyl-Lewis X
Target 6 Pathways Not Available
Target 6 Reactions Not Available
Target 6 Pfam Domain Function
Target 6 Signals
  • 1-41
Target 6 Transmembrane Regions
  • 772-795
Target 6 Essentiality Non-Essential
Target 6 GenBank ID Protein 183389 Link Image
Target 6 UniProtKB/Swiss-Prot ID P16109 Link Image
Target 6 UniProtKB/Swiss-Prot Entry Name LYAM3_HUMAN Link Image
Target 6 PDB ID 1G1S Link Image
Target 6 PDB File Show
Target 6 3D Structure
Target 6 Cellular Location
  • Membrane
  • single-pass type I membrane protein
Target 6 Gene Sequence >2493 bp 
ATGGCCAACTGCCAAATAGCCATCTTGTACCAGAGATTCCAGAGAGTGGTCTTTGGAATT
TCCCAACTCCTTTGCTTCAGTGCCCTGATCTCTGAACTAACAAACCAGAAAGAAGTGGCA
GCATGGACTTATCATTACAGCACAAAAGCATACTCATGGAATATTTCCCGTAAATACTGC
CAGAATCGCTACACAGACTTAGTGGCCATCCAGAATAAAAATGAAATTGATTACCTCAAT
AAGGTCCTACCCTACTACAGCTCCTACTACTGGATTGGGATCCGAAAGAACAATAAGACA
TGGACATGGGTGGGAACCAAAAAGGCTCTCACCAACGAGGCTGAGAACTGGGCTGATAAT
GAACCTAACAACAAAAGGAACAACGAGGACTGCGTGGAGATATACATCAAGAGTCCGTCA
GCCCCTGGCAAGTGGAATGATGAGCACTGCTTGAAGAAAAAGCACGCATTGTGTTACACA
GCCTCCTGCCAGGACATGTCCTGCAGCAAACAAGGAGAGTGCCTCGAGACCATCGGGAAC
TACACCTGCTCCTGTTACCCTGGATTCTATGGGCCAGAATGTGAATACGTGAGAGAGTGT
GGAGAACTTGAGCTCCCTCAACACGTGCTCATGAACTGCAGCCACCCTCTGGGAAACTTC
TCTTTTAACTCGCAGTGCAGCTTCCACTGCACTGACGGGTACCAAGTAAATGGGCCCAGC
AAGCTGGAATGCTTGGCTTCTGGAATCTGGACAAATAAGCCTCCACAGTGTTTAGCTGCC
CAGTGCCCACCCCTGAAGATTCCTGAACGAGGAAACATGATCTGCCTTCATTCTGCAAAA
GCATTCCAGCATCAGTCTAGCTGCAGCTTCAGTTGTGAAGAGGGATTTGCATTAGTTGGA
CCGGAAGTGGTGCAATGCACAGCCTCGGGGGTATGGACAGCCCCAGCCCCAGTGTGTAAA
GCTGTGCAGTGTCAGCACCTGGAAGCCCCCAGTGAAGGAACCATGGACTGTGTTCATCCG
CTCACTGCTTTTGCCTATGGCTCCAGCTGCAAATTTGAGTGCCAGCCCGGCTACAGAGTG
AGGGGCTTGGACATGCTCCGCTGCATTGACTCTGGACACTGGTCTGCACCCTTGCCAACC
TGTGAGGCTATTTCGTGTGAGCCGCTGGAGAGTCCTGTCCACGGAAGCATGGATTGCTCT
CCATCCTTGAGAGCGTTTCAGTATGACACCAACTGTAGCTTCCGCTGTGCTGAAGGTTTC
ATGCTGAGAGGAGCCGATATAGTTCGGTGTGATAACTTGGGACAGTGGACAGCACCAGCC
CCAGTCTGTCAAGCTTTGCAGTGCCAGGATCTCCCAGTTCCAAATGAGGCCCGGGTGAAC
TGCTCCCACCCCTTCGGTGCCTTTAGGTACCAGTCAGTCTGCAGCTTCACCTGCAATGAA
GGCTTGCTCCTGGTGGGAGCAAGTGTGCTACAGTGCTTGGCTACTGGAAACTGGAATTCT
GTTCCTCCAGAATGCCAAGCCATTCCCTGCACACCTTTGCTAAGCCCTCAGAATGGAACA
ATGACCTGTGTTCAACCTCTTGGAAGTTCCAGTTATAAATCCACATGTCAATTCATCTGT
GACGAGGGATATTCTTTGTCTGGACCAGAAAGATTGGATTGTACTCGATCGGGACGCTGG
ACAGACTCCCCACCAATGTGTGAAGCCATCAAGTGCCCAGAACTCTTTGCCCCAGAGCAG
GGCAGCCTGGATTGTTCTGACACTCGTGGAGAATTCAATGTTGGCTCCACCTGTCATTTC
TCTTGTAACAATGGCTTTAAGCTGGAGGGGCCCAATAATGTGGAATGCACAACTTCTGGA
AGATGGTCAGCTACTCCACCAACCTGCAAAGGCATAGCATCACTTCCTACTCCAGGGTTG
CAATGTCCAGCCCTCACCACTCCTGGGCAGGGAACCATGTACTGTAGGCATCATCCGGGA
ACCTTTGGTTTTAATACCACTTGTTACTTTGGCTGCAACGCTGGATTCACACTCATAGGA
GACAGCACTCTCAGCTGCAGACCTTCAGGACAATGGACAGCAGTAACTCCAGCATGCAGA
GCTGTGAAATGCTCAGAACTACATGTTAATAAGCCAATAGCGATGAACTGCTCCAACCTC
TGGGGAAACTTCAGTTATGGATCAATCTGCTCTTTCCATTGTCTAGAGGGCCAGTTACTT
AATGGCTCTGCACAAACAGCATGCCAAGAGAATGGCCACTGGTCAACTACCGTGCCAACC
TGCCAAGCAGGACCATTGACTATCCAGGAAGCCCTGACTTACTTTGGTGGAGCGGTGGCT
TCTACAATAGGTCTGATAATGGGTGGGACGCTCCTGGCTTTGCTAAGAAAGCGTTTCAGA
CAAAAAGATGATGGGAAATGCCCCTTGAATCCTCACAGCCACCTAGGAACATATGGAGTT
TTTACAAACGCTGCATTTGACCCGAGTCCTTAA
Target 6 GenBank Gene ID
Target 6 GeneCard ID SELP Link Image
Target 6 GenAtlas ID SELP Link Image
Target 6 HGNC ID HGNC:10721 Link Image
Target 6 Chromosome Location 1
Target 6 Locus 1q22-q25
Target 6 SNPs SNPJam Report Link Image
Target 6 General References
  1. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed Link Image]
  2. Florian V, Schluter T, Bohnensack R: A new member of the sorting nexin family interacts with the C-terminus of P-selectin. Biochem Biophys Res Commun. 2001 Mar 9;281(4):1045-50. [PubMed Link Image]
  3. Johnston GI, Cook RG, McEver RP: Cloning of GMP-140, a granule membrane protein of platelets and endothelium: sequence similarity to proteins involved in cell adhesion and inflammation. Cell. 1989 Mar 24;56(6):1033-44. [PubMed Link Image]
  4. Bajorath J, Stenkamp R, Aruffo A: Knowledge-based model building of proteins: concepts and examples. Protein Sci. 1993 Nov;2(11):1798-810. [PubMed Link Image]
  5. Fujimoto T, Stroud E, Whatley RE, Prescott SM, Muszbek L, Laposata M, McEver RP: P-selectin is acylated with palmitic acid and stearic acid at cysteine 766 through a thioester linkage. J Biol Chem. 1993 May 25;268(15):11394-400. [PubMed Link Image]
  6. Freedman SJ, Sanford DG, Bachovchin WW, Furie BC, Baleja JD, Furie B: Structure and function of the epidermal growth factor domain of P-selectin. Biochemistry. 1996 Oct 29;35(43):13733-44. [PubMed Link Image]
  7. Herrmann SM, Ricard S, Nicaud V, Mallet C, Evans A, Ruidavets JB, Arveiler D, Luc G, Cambien F: The P-selectin gene is highly polymorphic: reduced frequency of the Pro715 allele carriers in patients with myocardial infarction. Hum Mol Genet. 1998 Aug;7(8):1277-84. [PubMed Link Image]
Target 6 Drug References
  1. Monzavi-Karbassi B, Stanley JS, Hennings L, Jousheghany F, Artaud C, Shaaf S, Kieber-Emmons T: Chondroitin sulfate glycosaminoglycans as major P-selectin ligands on metastatic breast cancer cell lines. Int J Cancer. 2007 Mar 15;120(6):1179-91. [PubMed Link Image]
  2. Simonis D, Fritzsche J, Alban S, Bendas G: Kinetic analysis of heparin and glucan sulfates binding to P-selectin and its impact on the general understanding of selectin inhibition. Biochemistry. 2007 May 22;46(20):6156-64. Epub 2007 Apr 26. [PubMed Link Image]
  3. Maugeri N, Di Fabio G, Barbanti M, de Gaetano G, Donati MB, Cerletti C: Parnaparin, a low-molecular-weight heparin, prevents P-selectin-dependent formation of platelet-leukocyte aggregates in human whole blood. Thromb Haemost. 2007 Jun;97(6):965-73. [PubMed Link Image]
  4. Simonis D, Christ K, Alban S, Bendas G: Affinity and kinetics of different heparins binding to P- and L-selectin. Semin Thromb Hemost. 2007 Jul;33(5):534-9. [PubMed Link Image]
  5. Asberg AE, Videm V: Inhibition of platelet receptors involved in neutrophil-platelet interaction in model cardiopulmonary bypass. Artif Organs. 2007 Aug;31(8):617-26. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.