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Identification
NameCoagulation Factor IX
Accession NumberDB00100  (BIOD00038, BTD00038)
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
Protein chemical formulaC2041H3136N558O641S25
Protein average weight46548.2000
Sequences
>DB00100 sequence
YNSGKLEEFVQGNLERECMEEKCSFEEAREVFENTERTTEFWKQYVDGDQCESNPCLNGG
SCKDDINSYECWCPFGFEGKNCELDVTCNIKNGRCEQFCKNSADNKVVCSCTEGYRLAEN
QKSCEPAVPFPCGRVSVSQTSKLTRAEAVFPDVDYVNSTEAETILDNITQSTQSFNDFTR
VVGGEDAKPGQFPWQVVLNGKVDAFCGGSIVNEKWIVTAAHCVETGVKITVVAGEHNIEE
TEHTEQKRNVIRIIPHHNYNAAINKYNHDIALLELDEPLVLNSYVTPICIADKEYTNIFL
KFGSGYVSGWGRVFHKGRSALVLQYLRVPLVDRATCLRSTKFTIYNNMFCAGFHEGGRDS
CQGDSGGPHVTEVEGTSFLTGIISWGEECAMKGKYGIYTKVSRYVNWIKEKTKLT
Download FASTA Format
Synonyms
SynonymLanguageCode
Christmas factorNot AvailableNot Available
Coagulation factor IX precursorNot AvailableNot Available
Plasma thromboplastin componentNot AvailableNot Available
PTCNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
BenefixGenetics Institute
Brand mixturesNot Available
CategoriesNot Available
CAS number9001-28-9
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentPeptides
Alternative parentsNot Available
SubstituentsNot Available
Classification descriptionNot 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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
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
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption Not Available Not Available
Blood Brain Barrier Not Available Not Available
Caco-2 permeable Not Available Not Available
P-glycoprotein substrate Not Available Not Available
P-glycoprotein inhibitor I Not Available Not Available
P-glycoprotein inhibitor II Not Available Not Available
Renal organic cation transporter Not Available Not Available
CYP450 2C9 substrate Not Available Not Available
CYP450 2D6 substrate Not Available Not Available
CYP450 3A4 substrate Not Available Not Available
CYP450 1A2 substrate Not Available Not Available
CYP450 2C9 substrate Not Available Not Available
CYP450 2D6 substrate Not Available Not Available
CYP450 2C19 substrate Not Available Not Available
CYP450 3A4 substrate Not Available Not Available
CYP450 inhibitory promiscuity Not Available Not Available
Ames test Not Available Not Available
Carcinogenicity Not Available Not Available
Biodegradation Not Available Not Available
Rat acute toxicity Not Available Not applicable
hERG inhibition (predictor I) Not Available Not Available
hERG inhibition (predictor II) Not Available Not Available
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous
Prices
Unit descriptionCostUnit
Alphanine sd 250-1500 unit vial1.42USDvial
Mononine 1000 unit vial1.2USDvial
Mononine 500 unit vial1.2USDvial
Benefix 2000 unit vial1.12USDvial
Benefix 1000 unit vial1.0USDvial
Benefix 250 unit vial1.0USDvial
Benefix 500 unit vial1.0USDvial
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
Spectra
SpectraNot 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 Reference
  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
  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
External Links
ResourceLink
UniProtP00740
GenbankK02402
PharmGKBPA164744952
Drug Product Database2228998
RxListhttp://www.rxlist.com/cgi/generic2/factorix.htm
Drugs.comhttp://www.drugs.com/cdi/coagulation-factor-ix-injection-human.html
WikipediaFactor_IX
ATC CodesB02BD04
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSshow(125 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

1. Coagulation factor X

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: activator

Components

Name UniProt ID Details
Coagulation factor X P00742 Details

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
  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
  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
  4. London FS, Walsh PN: Zymogen factor IX potentiates factor IXa-catalyzed factor X activation. Biochemistry. 2000 Aug 15;39(32):9850-8. Pubmed
  5. Scandella DH: Properties of anti-factor VIII inhibitor antibodies in hemophilia A patients. Semin Thromb Hemost. 2000;26(2):137-42. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  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

2. Coagulation factor XI

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: ligand

Components

Name UniProt ID Details
Coagulation factor XI P03951 Details

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
  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
  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

3. Coagulation factor VII

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: ligand

Components

Name UniProt ID Details
Coagulation factor VII P08709 Details

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
  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
  3. Butenas S, van’t Veer C, Mann KG: “Normal” thrombin generation. Blood. 1999 Oct 1;94(7):2169-78. Pubmed
  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
  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
  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

4. Coagulation factor VIII

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: cofactor

Components

Name UniProt ID Details
Coagulation factor VIII P00451 Details

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
  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
  3. Federici AB: The factor VIII/von Willebrand factor complex: basic and clinical issues. Haematologica. 2003 Jun;88(6):EREP02. Pubmed
  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
  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
  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

5. Prothrombin

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Prothrombin P00734 Details

References:

  1. Butenas S, van’t Veer C, Mann KG: “Normal” thrombin generation. Blood. 1999 Oct 1;94(7):2169-78. Pubmed
  2. Kohler M: Thrombogenicity of prothrombin complex concentrates. Thromb Res. 1999 Aug 15;95(4 Suppl 1):S13-7. Pubmed
  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
  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
  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

6. Prolow-density lipoprotein receptor-related protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Prolow-density lipoprotein receptor-related protein 1 Q07954 Details

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
  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
  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

7. Vitamin K-dependent gamma-carboxylase

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Vitamin K-dependent gamma-carboxylase P38435 Details

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
  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
  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
  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
  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

Comments
Drug created on June 13, 2005 07:24 / Updated on September 13, 2013 10:49