DT-Web

DB00100 - Coagulation Factor IX


Identification
Name Coagulation Factor IX
Accession Number DB00100 (BIOD00038, BTD00038)
Type biotech
Description Human Factor IX protein, produced by recombinant DNA technology for use in therapy of factor IX deficiency, known as hemophilia B or Christmas disease. Coagulation Factor IX (Recombinant) is a glycoprotein with an approximate molecular mass of 55,000 Da consisting of 415 amino acids in a single chain. It has a primary amino acid sequence that is identical to the Ala 148 allelic form of plasma-derived factor IX.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 46548.2000
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication For treatment of hemophilia (Christmas disease).
Mechanism of action Coagulation Factor IX is an important protein in the process of hemostasis and normal blood clotting. Factor IX is plays an important intermediate role in the blood coagulation cascade. It is located within the blood plasma as a zymogen, an antecedent to enzymatic function, in its inactivated state. Factor IX is dependent on the presence of Vitamin K, and is activated to a serine protease by the function of Coagulation Factor XIa. Factor XIa cleaves the peptide bond associated with protein activation in Factor IX, leaving Factor IX with two exposed chains, a light chain and a heavy chain. These two chains are held together by several disulfide bonds that reinforce the structure of Factor IX's activated form. After being activated, Factor IX forms a complex with calcium ions, membrane phospholipids and Coagulation Factor VIII to activate Coagulation Factor X. The activation of Factor X then performs a similarly integral step in the blood coagulation cascade. The ultimate result of phenotypically normal coagulation factors is the creation of platelets for normal blood clotting.
Absorption Not Available
Protein binding Not Available
Biotransformation Not Available
Route of elimination Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Targets


Coagulation factor X
Name Coagulation factor X
Gene Name F10
Pharmacological action yes
Actions activator
References
  • Worfolk LA, Robinson RA, Tracy PB: Factor Xa interacts with two sites on monocytes with different functional activities. Blood. 1992 Oct 15;80(8):1989-97. - Pubmed
  • Jones KC, Mann KG: A model for the tissue factor pathway to thrombin. II. A mathematical simulation. J Biol Chem. 1994 Sep 16;269(37):23367-73. - Pubmed
  • Ambrosini G, Plescia J, Chu KC, High KA, Altieri DC: Activation-dependent exposure of the inter-EGF sequence Leu83-Leu88 in factor Xa mediates ligand binding to effector cell protease receptor-1. J Biol Chem. 1997 Mar 28;272(13):8340-5. - Pubmed
  • London FS, Walsh PN: Zymogen factor IX potentiates factor IXa-catalyzed factor X activation. Biochemistry. 2000 Aug 15;39(32):9850-8. - Pubmed
  • Scandella DH: Properties of anti-factor VIII inhibitor antibodies in hemophilia A patients. Semin Thromb Hemost. 2000;26(2):137-42. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • Di Scipio RG, Kurachi K, Davie EW: Activation of human factor IX (Christmas factor). J Clin Invest. 1978 Jun;61(6):1528-38. - Pubmed
DTHybrid score 1.7174
Coagulation factor XI
Name Coagulation factor XI
Gene Name F11
Pharmacological action yes
Actions ligand
References
  • Sun MF, Zhao M, Gailani D: Identification of amino acids in the factor XI apple 3 domain required for activation of factor IX. J Biol Chem. 1999 Dec 17;274(51):36373-8. - Pubmed
  • Gailani D, Ho D, Sun MF, Cheng Q, Walsh PN: Model for a factor IX activation complex on blood platelets: dimeric conformation of factor XIa is essential. Blood. 2001 May 15;97(10):3117-22. - Pubmed
  • Di Scipio RG, Kurachi K, Davie EW: Activation of human factor IX (Christmas factor). J Clin Invest. 1978 Jun;61(6):1528-38. - Pubmed
DTHybrid score 2.0243
Coagulation factor VII
Name Coagulation factor VII
Gene Name F7
Pharmacological action yes
Actions ligand
References
  • Baker DC, Robbe SL, Jacobson L, Manco-Johnson MJ, Holler L, Lefkowitz J: Hereditary deficiency of vitamin-K-dependent coagulation factors in Rambouillet sheep. Blood Coagul Fibrinolysis. 1999 Mar;10(2):75-80. - Pubmed
  • Hertzberg MS, Facey SL, Hogg PJ: An Arg/Ser substitution in the second epidermal growth factor-like module of factor IX introduces an O-linked carbohydrate and markedly impairs activation by factor XIa and factor VIIa/Tissue factor and catalytic efficiency of factor IXa. Blood. 1999 Jul 1;94(1):156-63. - Pubmed
  • Butenas S, van't Veer C, Mann KG: - Normal
  • Celie PH, Lenting PJ, Mertens K: Hydrophobic contact between the two epidermal growth factor-like domains of blood coagulation factor IX contributes to enzymatic activity. J Biol Chem. 2000 Jan 7;275(1):229-34. - Pubmed
  • Shord SS, Lindley CM: Coagulation products and their uses. Am J Health Syst Pharm. 2000 Aug 1;57(15):1403-17; quiz 1418-20. - Pubmed
  • Di Scipio RG, Kurachi K, Davie EW: Activation of human factor IX (Christmas factor). J Clin Invest. 1978 Jun;61(6):1528-38. - Pubmed
DTHybrid score 1.4526
Coagulation factor VIII
Name Coagulation factor VIII
Gene Name F8
Pharmacological action yes
Actions cofactor
References
  • Neels JG, Bovenschen N, van Zonneveld AJ, Lenting PJ: Interaction between factor VIII and LDL receptor-related protein. Modulation of coagulation? Trends Cardiovasc Med. 2000 Jan;10(1):8-14. - Pubmed
  • Carr ME Jr, Martin EJ, Kuhn JG, Seremetis SV: Effects of recombinant factor VIIa on platelet function and clot structure in blood with deficient prothrombin conversion. Thromb Haemost. 2003 May;89(5):803-11. - Pubmed
  • Federici AB: The factor VIII/von Willebrand factor complex: basic and clinical issues. Haematologica. 2003 Jun;88(6):EREP02. - Pubmed
  • Kalashnikova LA, Berkovskii AL, Dobrynina LA, Sergeeva EV, Kozlov AA, Aleksandrova EN, Nasonov EL: [Clotting factor VIII in Sneddon syndrome] Klin Med (Mosk). 2003;81(9):42-5. - Pubmed
  • Johansen RF, Sorensen B, Ingerslev J: Acquired haemophilia: dynamic whole blood coagulation utilized to guide haemostatic therapy. Haemophilia. 2006 Mar;12(2):190-7. - Pubmed
  • Di Scipio RG, Kurachi K, Davie EW: Activation of human factor IX (Christmas factor). J Clin Invest. 1978 Jun;61(6):1528-38. - Pubmed
DTHybrid score 0.4697
Prothrombin
Name Prothrombin
Gene Name F2
Pharmacological action unknown
Actions Not Available
References
  • Butenas S, van't Veer C, Mann KG: - Normal
  • Kohler M: Thrombogenicity of prothrombin complex concentrates. Thromb Res. 1999 Aug 15;95(4 Suppl 1):S13-7. - Pubmed
  • Seitz R, Dodt J: Virus safety of prothrombin complex concentrates and factor IX concentrates. Thromb Res. 1999 Aug 15;95(4 Suppl 1):S19-23. - Pubmed
  • Samis JA, Ramsey GD, Walker JB, Nesheim ME, Giles AR: Proteolytic processing of human coagulation factor IX by plasmin. Blood. 2000 Feb 1;95(3):943-51. - Pubmed
  • Bauer KA, Humphries S, Smillie B, Li L, Cooper JA, Barzegar S, Rosenberg RD, Miller GJ: Prothrombin activation is increased among asymptomatic carriers of the prothrombin G20210A and factor V Arg506Gln mutations. Thromb Haemost. 2000 Sep;84(3):396-400. - Pubmed
DTHybrid score 1.8962
Low-density lipoprotein receptor-related protein 1
Name Low-density lipoprotein receptor-related protein 1
Gene Name LRP1
Pharmacological action unknown
Actions Not Available
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Rohlena J, Kolkman JA, Boertjes RC, Mertens K, Lenting PJ: Residues Phe342-Asn346 of activated coagulation factor IX contribute to the interaction with low density lipoprotein receptor-related protein. J Biol Chem. 2003 Mar 14;278(11):9394-401. Epub 2003 Jan 9. - Pubmed
DTHybrid score 0.4441
Vitamin K-dependent gamma-carboxylase
Name Vitamin K-dependent gamma-carboxylase
Gene Name GGCX
Pharmacological action unknown
Actions Not Available
References
  • Lin PJ, Straight DL, Stafford DW: Binding of the factor IX gamma-carboxyglutamic acid domain to the vitamin K-dependent gamma-glutamyl carboxylase active site induces an allosteric effect that may ensure processive carboxylation and regulate the release of carboxylated product. J Biol Chem. 2004 Feb 20;279(8):6560-6. Epub 2003 Dec 2. - Pubmed
  • Wu SM, Mutucumarana VP, Geromanos S, Stafford DW: The propeptide binding site of the bovine gamma-glutamyl carboxylase. J Biol Chem. 1997 May 2;272(18):11718-22. - Pubmed
  • Rehemtulla A, Roth DA, Wasley LC, Kuliopulos A, Walsh CT, Furie B, Furie BC, Kaufman RJ: In vitro and in vivo functional characterization of bovine vitamin K-dependent gamma-carboxylase expressed in Chinese hamster ovary cells. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4611-5. - Pubmed
  • Stanley TB, Wu SM, Houben RJ, Mutucumarana VP, Stafford DW: Role of the propeptide and gamma-glutamic acid domain of factor IX for in vitro carboxylation by the vitamin K-dependent carboxylase. Biochemistry. 1998 Sep 22;37(38):13262-8. - Pubmed
  • Stanley TB, Stafford DW, Olivera BM, Bandyopadhyay PK: Identification of a vitamin K-dependent carboxylase in the venom duct of a Conus snail. FEBS Lett. 1997 Apr 21;407(1):85-8. - Pubmed
DTHybrid score 0.8323

Predictions


Id Partner name Gene Name Score
2139 Tissue factor F3 0.3373
798 Osteocalcin BGLAP 0.1561
267 Plasminogen activator inhibitor 1 SERPINE1 0.1206
1959 Platelet factor 4 PF4 0.115
3865 Serpin B6 SERPINB6 0.1149
1986 Ceruloplasmin CP 0.1149
1245 Vitamin K-dependent protein S PROS1 0.1131
1516 Calnexin CANX 0.1121
3176 Trypsin-1 PRSS1 0.1044
3830 Calreticulin CALR 0.1025
3833 Plasma serine protease inhibitor SERPINA5 0.1
1334 Tissue factor pathway inhibitor TFPI 0.0991
46 Coagulation factor V F5 0.0975
2021 Thrombomodulin THBD 0.097
2072 Endothelial protein C receptor PROCR 0.097
400 Coagulation factor IX F9 0.0831
5461 Coagulation factor IX F9 0.0831
3851 Serine protease hepsin HPN 0.0795
422 Vitamin K-dependent protein C PROC 0.0743
3842 Multiple coagulation factor deficiency protein 2 MCFD2 0.0646
3840 Asialoglycoprotein receptor 2 ASGR2 0.0646
3841 ERGIC-53 protein LMAN1 0.0646
1847 78 kDa glucose-regulated protein HSPA5 0.0646
1635 von Willebrand factor VWF 0.0646
3825 Tetranectin CLEC3B 0.0642
2111 Annexin A2 ANXA2 0.0642
3826 Keratin, type II cytoskeletal 8 KRT8 0.0642
1349 Plasminogen activator inhibitor 2 SERPINB2 0.0559
3839 Phytanoyl-CoA dioxygenase, peroxisomal PHYH 0.0545
309 Antithrombin-III SERPINC1 0.0533
791 Urokinase plasminogen activator surface receptor PLAUR 0.0466
595 Fibrinogen alpha chain FGA 0.0449
234 Plasminogen PLG 0.0405
1074 Urokinase-type plasminogen activator PLAU 0.0362
604 Vitamin K-dependent protein Z PROZ 0.0287
4081 Vitamin K epoxide reductase complex subunit 1-like protein 1 VKORC1L1 0.0287
243 Ribosyldihydronicotinamide dehydrogenase [quinone] NQO2 0.022
1757 Myeloperoxidase MPO 0.0201
787 Vitamin K epoxide reductase complex subunit 1 VKORC1 0.0191
3917 Methylenetetrahydrofolate reductase MTHFR 0.0173
2157 NAD(P)H dehydrogenase [quinone] 1 NQO1 0.0171
3119 Fimbrial protein pilE1 0.0168
1719 Heparanase HPSE 0.0164
6020 Aldehyde oxidase AOX1 0.0162
2058 P-selectin SELP 0.0156
3947 Xanthine dehydrogenase/oxidase XDH 0.0148
6182 Cytochrome P450 2J2 CYP2J2 0.0145
6564 Prephenate dehydrogenase tyrA 0.0122
6240 Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 PIN1 0.0122
5718 Cytochrome P450 2A6 CYP2A6 0.0116
4200 Cytochrome P450 1A2 CYP1A2 0.0112
6024 Cytochrome P450 1A1 CYP1A1 0.011
6013 Cytochrome P450 2E1 CYP2E1 0.0105
4118 Cytochrome P450 3A5 CYP3A5 0.0102
2331 HTH-type transcriptional regulator qacR qacR 0.01
6461 HTH-type transcriptional regulator qacR qacR 0.01
6828 TetR family transcriptional repressor LfrR lfrR 0.0095
256 Tyrosyl-tRNA synthetase, cytoplasmic YARS 0.0093
3384 Macrophage migration inhibitory factor MIF 0.009
4512 Cytochrome P450 3A4 CYP3A4 0.0083
1588 Multidrug resistance protein 1 ABCB1 0.0079
4757 Cytochrome P450 2C9 CYP2C9 0.0068
4165 P2Y purinoceptor 2 P2RY2 0.0047
4024 Mitochondrial glutamate carrier 2 SLC25A18 0.0042
4025 Mitochondrial glutamate carrier 1 SLC25A22 0.0042
4022 Glutamate--ammonia ligase domain-containing protein 1 LGSN 0.0042
4019 Excitatory amino acid transporter 4 SLC1A6 0.0042
919 Glutamate receptor, ionotropic kainate 4 GRIK4 0.0042
920 Glutamate receptor, ionotropic kainate 5 GRIK5 0.0042
4026 Aspartyl aminopeptidase DNPEP 0.0042
4021 Probable glutamyl-tRNA synthetase, mitochondrial EARS2 0.0042
4023 N-acetylglutamate synthase, mitochondrial NAGS 0.0042
1912 Excitatory amino acid transporter 1 SLC1A3 0.0042
4016 Excitatory amino acid transporter 5 SLC1A7 0.0042
1047 Excitatory amino acid transporter 2 SLC1A2 0.0042
922 Glutamate receptor 4 GRIA4 0.0042
664 Glutamate decarboxylase 2 GAD2 0.0042
3890 Glutamate decarboxylase 2 GAD2 0.0042
926 Metabotropic glutamate receptor 7 GRM7 0.0042
924 Glutamate receptor, ionotropic kainate 3 GRIK3 0.0042
915 Delta 1-pyrroline-5-carboxylate synthetase ALDH18A1 0.0042
927 Metabotropic glutamate receptor 8 GRM8 0.0042
925 Metabotropic glutamate receptor 4 GRM4 0.0042
4020 Glutamyl aminopeptidase ENPEP 0.0042
4018 Glutamate receptor delta-2 subunit GRID2 0.0042
4027 Glutamate receptor delta-1 subunit GRID1 0.0042
4017 5-oxoprolinase OPLAH 0.0042
2654 Complement control protein C3L 0.0037
917 Glutaminase kidney isoform, mitochondrial GLS 0.0036
355 GMP synthase [glutamine-hydrolyzing] GMPS 0.0036
4353 GMP synthase [glutamine-hydrolyzing] guaA 0.0036
3991 Glutamine-dependent NAD(+) synthetase NADSYN1 0.0036
3984 Probable glutamyl-tRNA(Gln) amidotransferase subunit B, mitochondrial PET112L 0.0036
5 Glutaminase liver isoform, mitochondrial GLS2 0.0036
665 Phosphoserine aminotransferase PSAT1 0.0036
4652 Phosphoserine aminotransferase serC 0.0036
668 Glutamate--cysteine ligase regulatory subunit GCLM 0.0036
801 Kynurenine/alpha-aminoadipate aminotransferase mitochondrial AADAT 0.0036
3982 Phosphoribosylformylglycinamidine synthase PFAS 0.0036
5261 Phosphoribosylformylglycinamidine synthase purL 0.0036
3895 Kynurenine--oxoglutarate transaminase 3 CCBL2 0.0036
420 Glutamate decarboxylase 1 GAD1 0.0036
3900 Glutamate decarboxylase 1 GAD1 0.0036
830 Glutamate dehydrogenase 2, mitochondrial GLUD2 0.0035
382 Glutamate receptor, ionotropic kainate 1 GRIK1 0.0035
430 Follicle-stimulating hormone receptor FSHR 0.0034
5766 NAD-dependent deacetylase sirtuin-5 SIRT5 0.0034
625 Glutamate carboxypeptidase 2 FOLH1 0.0033
186 Glutamate--cysteine ligase catalytic subunit GCLC 0.0033
916 Metabotropic glutamate receptor 1 GRM1 0.0033
3877 Growth-inhibiting protein 18 GIG18 0.0033
1671 Excitatory amino acid transporter 3 SLC1A1 0.0033
923 Glutamate receptor 3 GRIA3 0.0032
5455 Arylsulfatase A ARSA 0.0032
763 Tyrosine aminotransferase TAT 0.0031
5493 Tyrosine aminotransferase Not Available 0.0031
773 Folylpolyglutamate synthase, mitochondrial FPGS 0.0031
914 Formimidoyltransferase-cyclodeaminase FTCD 0.0031
735 Alanine aminotransferase 1 GPT 0.0031
3904 Alanine aminotransferase 2 GPT2 0.0031
426 Aspartate aminotransferase, mitochondrial GOT2 0.0031
4604 Liver carboxylesterase 1 CES1 0.0031
439 Glutamate [NMDA] receptor subunit epsilon-4 GRIN2D 0.0031
505 Glutamate [NMDA] receptor subunit epsilon-3 GRIN2C 0.003
201 Glutamate dehydrogenase 1, mitochondrial GLUD1 0.003
83 Alpha-aminoadipic semialdehyde synthase, mitochondrial AASS 0.003
586 Aspartate aminotransferase, cytoplasmic GOT1 0.0029
242 Asparagine synthetase [glutamine-hydrolyzing] ASNS 0.0029
591 Glutamate [NMDA] receptor subunit 3B GRIN3B 0.0029
210 Bifunctional aminoacyl-tRNA synthetase [Includes: Glutamyl-tRNA synthetase EPRS 0.0029
814 Ryanodine receptor 1 RYR1 0.0029
464 Glutamate [NMDA] receptor subunit epsilon-2 GRIN2B 0.0028
705 Glutamate receptor 1 GRIA1 0.0028
574 Branched-chain-amino-acid aminotransferase, cytosolic BCAT1 0.0027
795 Branched-chain-amino-acid aminotransferase, mitochondrial BCAT2 0.0027
33 Cystine/glutamate transporter SLC7A11 0.0027
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0027
837 Glutamate [NMDA] receptor subunit epsilon-1 GRIN2A 0.0027
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0027
401 Glutamate [NMDA] receptor subunit zeta-1 GRIN1 0.0027
3426 Glutamine synthetase glnA 0.0027
3987 Glutamine synthetase GLUL 0.0027
2981 Phospholipase A2, membrane associated PLA2G2A 0.0026
280 4-aminobutyrate aminotransferase, mitochondrial ABAT 0.0026
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0025
723 Cytosolic phospholipase A2 PLA2G4A 0.0023
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.0022
4924 Cytochrome P450 2C8 CYP2C8 0.0022
918 Glutamate receptor, ionotropic kainate 2 GRIK2 0.0022
738 Monocarboxylate transporter 1 SLC16A1 0.0021
6016 Cytochrome P450 2C19 CYP2C19 0.0021
6151 Monocarboxylate transporter 10 SLC16A10 0.002
921 Glutamate receptor 2 GRIA2 0.0019
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