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Identification
NameCoagulation Factor IX
Accession NumberDB00100  (BTD00038, BIOD00038)
TypeBiotech
GroupsApproved
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.

Protein structureDb00100
Related Articles
Protein chemical formulaC2041H3136N558O641S25
Protein average weight46548.2 Da
Sequences
>DB00100 sequence
YNSGKLEEFVQGNLERECMEEKCSFEEAREVFENTERTTEFWKQYVDGDQCESNPCLNGG
SCKDDINSYECWCPFGFEGKNCELDVTCNIKNGRCEQFCKNSADNKVVCSCTEGYRLAEN
QKSCEPAVPFPCGRVSVSQTSKLTRAEAVFPDVDYVNSTEAETILDNITQSTQSFNDFTR
VVGGEDAKPGQFPWQVVLNGKVDAFCGGSIVNEKWIVTAAHCVETGVKITVVAGEHNIEE
TEHTEQKRNVIRIIPHHNYNAAINKYNHDIALLELDEPLVLNSYVTPICIADKEYTNIFL
KFGSGYVSGWGRVFHKGRSALVLQYLRVPLVDRATCLRSTKFTIYNNMFCAGFHEGGRDS
CQGDSGGPHVTEVEGTSFLTGIISWGEECAMKGKYGIYTKVSRYVNWIKEKTKLT
Download FASTA Format
Synonyms
Coagulation factor IX (human)
Coagulation factor IX (recombinant)
Coagulation factor IX human
Coagulation factor IX recombinant human
Factor IX (Human)
Factor IX (Recombinant)
Factor IX, recombinant
Factor IX,recombinant
Nonacog alfa
Recombinant factor IX
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Alphanine SdkitintravenousGRIFOLS USA, LLC1990-12-31Not applicableUs
Alphanine SdkitintravenousGRIFOLS USA, LLC1990-12-31Not applicableUs
Alphanine SdkitintravenousGRIFOLS USA, LLC1990-12-31Not applicableUs
BebulinkitBaxter Healthcare Corporation1992-08-19Not applicableUs
Bebulin VhkitBaxter Healthcare Corporation2011-03-16Not applicableUs
Benefixpowder for solution1000 unitintravenousPfizer Canada Inc2007-04-14Not applicableCanada
BenefixkitWyeth Bio Pharma Division Of Wyeth Pharmaceuticals Inc., A Subsidiary Of Pfizer Inc.2012-02-01Not applicableUs
Benefixpowder for solution500 unitintravenousPfizer Canada Inc2007-04-14Not applicableCanada
BenefixkitWyeth Bio Pharma Division Of Wyeth Pharmaceuticals Inc., A Subsidiary Of Pfizer Inc.1997-02-01Not applicableUs
Benefixpowder for solution250 unitintravenousPfizer Canada Inc2007-04-14Not applicableCanada
BenefixkitWyeth Bio Pharma Division Of Wyeth Pharmaceuticals Inc., A Subsidiary Of Pfizer Inc.1997-02-01Not applicableUs
BenefixkitWyeth Bio Pharma Division Of Wyeth Pharmaceuticals Inc., A Subsidiary Of Pfizer Inc.1997-02-01Not applicableUs
BenefixkitWyeth Bio Pharma Division Of Wyeth Pharmaceuticals Inc., A Subsidiary Of Pfizer Inc.1997-02-01Not applicableUs
Benefixpowder for solution3000 unitintravenousPfizer Canada Inc2013-02-12Not applicableCanada
Benefixpowder for solution2000 unitintravenousPfizer Canada Inc2008-07-12Not applicableCanada
IdelvionkitCsl Behring Recombinant Facility Ag2016-03-04Not applicableUs
IdelvionkitCsl Behring Recombinant Facility Ag2016-03-04Not applicableUs
IdelvionkitCsl Behring Recombinant Facility Ag2016-03-04Not applicableUs
IdelvionkitCsl Behring Recombinant Facility Ag2016-03-04Not applicableUs
Immunine Vhpowder for solution720 unitintravenousBaxalta Canada Corporation1996-10-18Not applicableCanada
IxinitykitCangene Bio Pharma2015-05-01Not applicableUs
IxinitykitCangene Bio Pharma2015-05-01Not applicableUs
IxinitykitCangene Bio Pharma2015-05-01Not applicableUs
MononinekitCSL Behring LLC1992-08-20Not applicableUs
MononinekitCSL Behring LLC1992-08-20Not applicableUs
RixubiskitBaxter Healthcare Corporation2013-06-26Not applicableUs
RixubiskitBaxter Healthcare Corporation2013-06-26Not applicableUs
RixubiskitBaxter Healthcare Corporation2013-06-26Not applicableUs
RixubiskitBaxter Healthcare Corporation2013-06-26Not applicableUs
RixubiskitBaxter Healthcare Corporation2013-06-26Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixtures
NameLabellerIngredients
Benefix - (250iu)Wyeth Canada
Benefix - (500iu)Wyeth Canada
Benefix -(1000iu)Wyeth Canada
SaltsNot Available
Categories
UNII382L14738L
CAS number181054-95-5
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available
Pharmacology
IndicationFor treatment of hemophilia (Christmas disease).
PharmacodynamicsBinds vitamin K and factor VIIIa. Cleaves the Arg-Ile bond in factor X to form active factor Xa. Plays a key role in blood coagulation and clotting. Injections of factor IX are used to treat hemophilia B, which is sometimes called Christmas disease. AlphaNine is injected to increase plasma levels of Factor IX and can temporarily correct this coagulation defect.
Mechanism of actionCoagulation 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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half life19.4 ± 5.4 hours (range from 11 to 36 hours)
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Kitintravenous
Powder for solutionintravenous1000 unit
Powder for solutionintravenous2000 unit
Powder for solutionintravenous250 unit
Powder for solutionintravenous3000 unit
Powder for solutionintravenous500 unit
Kit; liquid; powder for solutionintravenous
Powder for solutionintravenous720 unit
Kit
Prices
Unit descriptionCostUnit
Alphanine sd 250-1500 unit vial1.42USD vial
Mononine 1000 unit vial1.2USD vial
Mononine 500 unit vial1.2USD vial
Benefix 2000 unit vial1.12USD vial
Benefix 1000 unit vial1.0USD vial
Benefix 250 unit vial1.0USD vial
Benefix 500 unit vial1.0USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateLiquid
Experimental Properties
PropertyValueSource
melting point54 °CLink, R.P., Castellino, F.J. Arch. Biochem. Biophsy. 227:259-265 (1983)
hydrophobicity-0.431Not Available
isoelectric point5.20Not Available
References
Synthesis Reference

Volker Schellenberger, Joshua Silverman, Willem Stemmer, Chia-wei Wang, Benjamin Spink, Nathan Geething, Wayne To, “Coagulation factor IX compositions and methods of making and using same.” U.S. Patent US20110046060, issued February 24, 2011.

US20110046060
General References
  1. BIGGS R, DOUGLAS AS, MACFARLANE RG, DACIE JV, PITNEY WR, MERSKEY: Christmas disease: a condition previously mistaken for haemophilia. Br Med J. 1952 Dec 27;2(4799):1378-82. [PubMed:12997790 ]
  2. Kurachi K, Davie EW: Isolation and characterization of a cDNA coding for human factor IX. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6461-4. [PubMed:6959130 ]
External Links
ATC CodesB02BD01B02BD04B02BD09
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSDownload (125 KB)
Interactions
Drug Interactions
Drug
Aminocaproic AcidThe risk or severity of adverse effects can be increased when Aminocaproic Acid is combined with Coagulation Factor IX.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
activator
General Function:
Serine-type endopeptidase activity
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.
Gene Name:
F10
Uniprot ID:
P00742
Molecular Weight:
54731.255 Da
References
  1. 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:1391956 ]
  2. 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:8083242 ]
  3. 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:9079657 ]
  4. London FS, Walsh PN: Zymogen factor IX potentiates factor IXa-catalyzed factor X activation. Biochemistry. 2000 Aug 15;39(32):9850-8. [PubMed:10933803 ]
  5. Scandella DH: Properties of anti-factor VIII inhibitor antibodies in hemophilia A patients. Semin Thromb Hemost. 2000;26(2):137-42. [PubMed:10919405 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  7. Di Scipio RG, Kurachi K, Davie EW: Activation of human factor IX (Christmas factor). J Clin Invest. 1978 Jun;61(6):1528-38. [PubMed:659613 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
ligand
General Function:
Serine-type endopeptidase activity
Specific Function:
Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX.
Gene Name:
F11
Uniprot ID:
P03951
Molecular Weight:
70108.56 Da
References
  1. 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:10593931 ]
  2. 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:11342438 ]
  3. Di Scipio RG, Kurachi K, Davie EW: Activation of human factor IX (Christmas factor). J Clin Invest. 1978 Jun;61(6):1528-38. [PubMed:659613 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
ligand
General Function:
Serine-type peptidase activity
Specific Function:
Initiates the extrinsic pathway of blood coagulation. Serine protease that circulates in the blood in a zymogen form. Factor VII is converted to factor VIIa by factor Xa, factor XIIa, factor IXa, or thrombin by minor proteolysis. In the presence of tissue factor and calcium ions, factor VIIa then converts factor X to factor Xa by limited proteolysis. Factor VIIa will also convert factor IX to f...
Gene Name:
F7
Uniprot ID:
P08709
Molecular Weight:
51593.465 Da
References
  1. 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:10192655 ]
  2. 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:10381508 ]
  3. Butenas S, van't Veer C, Mann KG: "Normal" thrombin generation. Blood. 1999 Oct 1;94(7):2169-78. [PubMed:10498586 ]
  4. 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:10617609 ]
  5. 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:10938981 ]
  6. Di Scipio RG, Kurachi K, Davie EW: Activation of human factor IX (Christmas factor). J Clin Invest. 1978 Jun;61(6):1528-38. [PubMed:659613 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
cofactor
General Function:
Oxidoreductase activity
Specific Function:
Factor VIII, along with calcium and phospholipid, acts as a cofactor for factor IXa when it converts factor X to the activated form, factor Xa.
Gene Name:
F8
Uniprot ID:
P00451
Molecular Weight:
267007.42 Da
References
  1. 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:11150722 ]
  2. 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:12719776 ]
  3. Federici AB: The factor VIII/von Willebrand factor complex: basic and clinical issues. Haematologica. 2003 Jun;88(6):EREP02. [PubMed:12826528 ]
  4. 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:14598591 ]
  5. 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:16476097 ]
  6. Di Scipio RG, Kurachi K, Davie EW: Activation of human factor IX (Christmas factor). J Clin Invest. 1978 Jun;61(6):1528-38. [PubMed:659613 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Thrombospondin receptor activity
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. Functions in blood homeostasis, inflammation and wound healing.
Gene Name:
F2
Uniprot ID:
P00734
Molecular Weight:
70036.295 Da
References
  1. Butenas S, van't Veer C, Mann KG: "Normal" thrombin generation. Blood. 1999 Oct 1;94(7):2169-78. [PubMed:10498586 ]
  2. Kohler M: Thrombogenicity of prothrombin complex concentrates. Thromb Res. 1999 Aug 15;95(4 Suppl 1):S13-7. [PubMed:10499904 ]
  3. 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:10499905 ]
  4. 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:10648407 ]
  5. 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:11019961 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Receptor activity
Specific Function:
Endocytic receptor involved in endocytosis and in phagocytosis of apoptotic cells. Required for early embryonic development. Involved in cellular lipid homeostasis. Involved in the plasma clearance of chylomicron remnants and activated LRPAP1 (alpha 2-macroglobulin), as well as the local metabolism of complexes between plasminogen activators and their endogenous inhibitors. May modulate cellula...
Gene Name:
LRP1
Uniprot ID:
Q07954
Molecular Weight:
504601.695 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. 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:17016423 ]
  3. 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:12522212 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Gamma-glutamyl carboxylase activity
Specific Function:
Mediates the vitamin K-dependent carboxylation of glutamate residues to calcium-binding gamma-carboxyglutamate (Gla) residues with the concomitant conversion of the reduced hydroquinone form of vitamin K to vitamin K epoxide.
Gene Name:
GGCX
Uniprot ID:
P38435
Molecular Weight:
87560.065 Da
References
  1. 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:14660587 ]
  2. 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:9115224 ]
  3. 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:8506307 ]
  4. 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:9748333 ]
  5. 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:9141486 ]
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Drug created on June 13, 2005 07:24 / Updated on August 19, 2016 10:43