Editing Factor IX (section)

== Domain architecture ==

[[Factor VII|Factors VII]], IX, and [[Factor X|X]] all play key roles in [[blood coagulation]] and also share a common domain architecture.<ref name="pmid11723140">{{cite journal | vauthors = Zhong D, Bajaj MS, Schmidt AE, Bajaj SP | title = The N-terminal epidermal growth factor-like domain in factor IX and factor X represents an important recognition motif for binding to tissue factor | journal = The Journal of Biological Chemistry | volume = 277 | issue = 5 | pages = 3622–31 | date = Feb 2002 | pmid = 11723140 | doi = 10.1074/jbc.M111202200 | doi-access = free }}</ref> The factor IX protein is composed of four [[protein domain]]s: the [[Gla domain]], two tandem copies of the [[EGF-like domain|EGF domain]] and a C-terminal [[trypsin]]-like peptidase domain which carries out the catalytic cleavage.

[[Image:Factor IX.png|thumb|Human factor IX protein domain architecture, where each protein domain is represented by a coloured box|400px|left]]

The N-terminal EGF domain has been shown to at least in part be responsible for binding [[tissue factor]].<ref name="pmid11723140"/> Wilkinson ''et al''. conclude that residues 88 to 109 of the second EGF domain mediate binding to platelets and assembly of the factor X activating complex.<ref name="pmid11714704">{{cite journal | vauthors = Wilkinson FH, Ahmad SS, Walsh PN | title = The factor IXa second epidermal growth factor (EGF2) domain mediates platelet binding and assembly of the factor X activating complex | journal = The Journal of Biological Chemistry | volume = 277 | issue = 8 | pages = 5734–41 | date = Feb 2002 | pmid = 11714704 | doi = 10.1074/jbc.M107753200 | doi-access = free }}</ref>

The structures of all four domains have been solved. A structure of the two EGF domains and the trypsin-like domain was determined for the pig protein.<ref name="pmid7568220">{{cite journal | vauthors = Brandstetter H, Bauer M, Huber R, Lollar P, Bode W | title = X-ray structure of clotting factor IXa: active site and module structure related to Xase activity and hemophilia B | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 92 | issue = 21 | pages = 9796–800 | date = Oct 1995 | pmid = 7568220 | pmc = 40889 | doi = 10.1073/pnas.92.21.9796 | bibcode = 1995PNAS...92.9796B | doi-access = free }}</ref> The structure of the Gla domain, which is responsible for Ca(II)-dependent phospholipid binding, was also determined by [[NMR]].<ref name="pmid7547952">{{cite journal | vauthors = Freedman SJ, Furie BC, Furie B, Baleja JD | title = Structure of the calcium ion-bound gamma-carboxyglutamic acid-rich domain of factor IX | journal = Biochemistry | volume = 34 | issue = 38 | pages = 12126–37 | date = Sep 1995 | pmid = 7547952 | doi = 10.1021/bi00038a005 }}</ref>

Several structures of 'super active' mutants have been solved,<ref name="pmid20004170">{{cite journal | vauthors = Zögg T, Brandstetter H | title = Structural basis of the cofactor- and substrate-assisted activation of human coagulation factor IXa | journal = Structure | volume = 17 | issue = 12 | pages = 1669–78 | date = Dec 2009 | pmid = 20004170 | doi = 10.1016/j.str.2009.10.011 | doi-access = free }}</ref> which reveal the nature of factor IX activation by other proteins in the clotting cascade.