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| Coagulation factor IX (plasma thromboplastic component, Christmas disease, hemophilia B) |
PDB rendering based on 1cfh. |
| Available structures |
| 1cfh, 1cfi, 1edm, 1ixa, 1j34, 1j35, 1mgx, 1nl0, 1rfn |
| Identifiers |
| Symbols |
F9; FIX; GLA domain; HEMB; MGC129641; MGC129642; PTC |
| External IDs |
OMIM: 306900 MGI: 88384 HomoloGene: 106 GeneCards: F9 Gene |
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| RNA expression pattern |
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| More reference expression data |
| Orthologs |
| Species |
Human |
Mouse |
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| Entrez |
2158 |
14071 |
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| Ensembl |
ENSG00000101981 |
ENSMUSG00000031138 |
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| UniProt |
P00740 |
A0JLY3 |
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| RefSeq (mRNA) |
NM_000133 |
NM_007979 |
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| RefSeq (protein) |
NP_000124 |
NP_032005 |
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| Location (UCSC) |
Chr X:
138.44 - 138.47 Mb |
Chr X:
56.35 - 56.38 Mb |
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| PubMed search |
[1] |
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Factor IX (or Christmas factor) is one of the serine proteases (EC 3.4.21.22) of the coagulation system; it belongs to peptidase family S1. Deficiency of this protein causes hemophilia B. It was discovered after a young boy named Stephen Christmas was found to be lacking this exact factor, leading to hemophilia, in 1952.[1]
[edit] Physiology
Factor IX is inactive unless activated by factor XIa (of the contact pathway) or factor VIIa (of the tissue factor pathway). When activated into factor IXa, in the presence of Ca2+, membrane phospholipids, and a Factor VIII cofactor, it hydrolyses one arginine-isoleucine bond in factor X to form factor Xa.
[edit] Genetics
The gene for factor IX is located on the X chromosome (Xq27.1-q27.2). It was first cloned in 1982 by Kotoku Kurachi and Earl Davie.[2]
Polly, a transgenic cloned Poll Dorset sheep carrying the gene for factor IX, was produced by Dr Ian Wilmut at the Roslin Institute in 1997.[3]
[edit] Role in disease
Deficiency of factor IX causes Christmas disease (hemophilia B). Over 100 mutations of factor IX have been described; some cause no symptoms, but many lead to a significant bleeding disorder.
Some rare mutations of factor IX result in elevated clotting activity, and can result in clotting diseases, such as deep vein thrombosis.[4]
[edit] References
- ^ Biggs RA, Douglas AS, MacFarlane RG, Dacie JV, Pittney WR, Merskey C, O'Brien JR. Christmas disease: a condition previously mistaken for haemophilia. Br Med J 1952;2:1378-1382. PMID 12997790.
- ^ Kurachi K, Davie E (1982). "Isolation and characterization of a cDNA coding for human factor IX". Proc Natl Acad Sci USA 79 (21): 6461–4. doi:10.1073/pnas.79.21.6461. PMID 6959130.
- ^ Nicholl D. (2002). An Introduction to Genetic Engineering Second Edition. Cambridge University Press. p. 257.
- ^ Simioni P, Tormene D, Tognin G, Gavasso S, Bulato C, Iacobelli NP, Finn JD, Spiezia L, Radu C, Arruda VR (October 2009). "X-linked thrombophilia with a mutant factor IX (factor IX Padua)". N. Engl. J. Med. 361 (17): 1671–5. doi:10.1056/NEJMoa0904377. PMID 19846852.
[edit] Further reading
- Davie EW, Fujikawa K (1975). "Basic mechanisms in blood coagulation". Annu. Rev. Biochem. 44: 799–829. doi:10.1146/annurev.bi.44.070175.004055. PMID 237463.
- Sommer SS (1992). "Assessing the underlying pattern of human germline mutations: lessons from the factor IX gene". FASEB J. 6 (10): 2767–74. PMID 1634040.
- Lenting PJ, van Mourik JA, Mertens K (1999). "The life cycle of coagulation factor VIII in view of its structure and function". Blood 92 (11): 3983–96. PMID 9834200.
- Lowe GD (2002). "Factor IX and thrombosis". Br. J. Haematol. 115 (3): 507–13. doi:10.1046/j.1365-2141.2001.03186.x. PMID 11736930.
- O'Connell NM (2004). "Factor XI deficiency--from molecular genetics to clinical management". Blood Coagul. Fibrinolysis 14 Suppl 1: S59–64. PMID 14567539.
- Du X (2007). "Signaling and regulation of the platelet glycoprotein Ib-IX-V complex". Curr. Opin. Hematol. 14 (3): 262–9. doi:10.1097/MOH.0b013e3280dce51a. PMID 17414217.
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PDB Gallery |
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1cfh: STRUCTURE OF THE METAL-FREE GAMMA-CARBOXYGLUTAMIC ACID-RICH MEMBRANE BINDING REGION OF FACTOR IX BY TWO-DIMENSIONAL NMR SPECTROSCOPY
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1cfi: NMR STRUCTURE OF CALCIUM ION-BOUND GAMMA-CARBOXY-GLUTAMIC ACID-RICH DOMAIN OF FACTOR IX
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1edm: EPIDERMAL GROWTH FACTOR-LIKE DOMAIN FROM HUMAN FACTOR IX
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1ixa: THE THREE-DIMENSIONAL STRUCTURE OF THE FIRST EGF-LIKE MODULE OF HUMAN FACTOR IX: COMPARISON WITH EGF AND TGF-A
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1j34: Crystal Structure of Mg(II)-and Ca(II)-bound Gla Domain of Factor IX Complexed with Binding Protein
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1j35: Crystal Structure of Ca(II)-bound Gla Domain of Factor IX Complexed with Binding Protein
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1mgx: COAGULATION FACTOR, MG(II), NMR, 7 STRUCTURES (BACKBONE ATOMS ONLY)
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1nl0: Crystal structure of human factor IX Gla domain in complex of an inhibitory antibody, 10C12
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1rfn: HUMAN COAGULATION FACTOR IXA IN COMPLEX WITH P-AMINO BENZAMIDINE
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Endopeptidases: serine proteases/serine endopeptidases (EC 3.4.21) |
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| Digestive enzymes |
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| Coagulation |
factors: Thrombin · Factor VIIa · Factor IXa · Factor Xa · Factor XIa · Factor XIIa · Kallikrein ( PSA, KLK1, KLK2, KLK3, KLK4, KLK5, KLK6, KLK7, KLK8, KLK9, KLK10, KLK11, KLK12, KLK13, KLK14, KLK15)
fibrinolysis: Plasmin · Plasminogen activator ( Tissue plasminogen activator · Urinary plasminogen activator)
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| Complement system |
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| Other immune system |
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| Venombin |
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| Other |
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