Sandbox Reserved 1482: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 23: | Line 23: | ||
== Function == | == Function == | ||
Factor VIII plays a central role in blood coagulation | ====Factor VIII plays a central role in blood coagulation==== | ||
| Line 29: | Line 29: | ||
The coagulation process | ====The coagulation process==== | ||
In response to an injury, the coagulation factor VIII is separated from von Willebrand factor. The active form is called “Factor VIIIa” and is obtained by a proteolytic cleavage of the B-domain of Factor VIII by thrombin <sup>[8,9]</sup>. Then the two remaining chains are linked together thanks to a metal link (probably calcium ion) <sup>[9]</sup>. | In response to an injury, the coagulation factor VIII is separated from von Willebrand factor. The active form is called “Factor VIIIa” and is obtained by a proteolytic cleavage of the B-domain of Factor VIII by thrombin <sup>[8,9]</sup>. Then the two remaining chains are linked together thanks to a metal link (probably calcium ion) <sup>[9]</sup>. | ||
| Line 41: | Line 41: | ||
== Structure == | == Structure == | ||
====Primary Structure==== | |||
In humans, factor VIII is encoded by the F8 gene <sup>[1,2,9]</sup>. This gene maps on the most distant band of the long arm of the X-chromosome (region Xq28). It is 186 kb in size (0.1 % of the whole size of the chromosome) and contains 26 exons <sup>[4]</sup>. | In humans, factor VIII is encoded by the F8 gene <sup>[1,2,9]</sup>. This gene maps on the most distant band of the long arm of the X-chromosome (region Xq28). It is 186 kb in size (0.1 % of the whole size of the chromosome) and contains 26 exons <sup>[4]</sup>. | ||
====Secondary Structure==== | |||
Factor VIII protein is composed of six globular domains: A<sub>1</sub>-A<sub>2</sub>-B-A<sub>3</sub>-C<sub>1</sub>-C<sub>2</sub> and contains one Ca<sup>2+</sup> and two Cu<sup>2+</sup> ions. It has a molecular weight of 330 kDa [1,9,14]. | Factor VIII protein is composed of six globular domains: A<sub>1</sub>-A<sub>2</sub>-B-A<sub>3</sub>-C<sub>1</sub>-C<sub>2</sub> and contains one Ca<sup>2+</sup> and two Cu<sup>2+</sup> ions. It has a molecular weight of 330 kDa [1,9,14]. | ||
| Line 67: | Line 67: | ||
====Ligands==== | |||
Alpha-D-mannose, calcium ion (Ca<sup>2+</sup>), copper ion (Cu<sup>2+</sup>) and N-acetl-D-glucosamine are the four ligands the factor VIII is able to bind to <sup>[2]</sup>. | Alpha-D-mannose, calcium ion (Ca<sup>2+</sup>), copper ion (Cu<sup>2+</sup>) and N-acetl-D-glucosamine are the four ligands the factor VIII is able to bind to <sup>[2]</sup>. | ||
In factor VIII there are two copper ions and their binding sites are located internally within the A<sub>3</sub> and the A<sub>1</sub> domain. In the latter, there is another ligand, a single calcium ion, bound to its binding site <sup>[9]</sup>. | In factor VIII there are two copper ions and their binding sites are located internally within the A<sub>3</sub> and the A<sub>1</sub> domain. In the latter, there is another ligand, a single calcium ion, bound to its binding site <sup>[9]</sup>. | ||
| Line 82: | Line 82: | ||
Inheritance | ====Inheritance==== | ||
Hemophilia A is inherited in an X-linked recessive manner: | Hemophilia A is inherited in an X-linked recessive manner: | ||
Females inherit two X chromosomes, one from their mother and one from their father (XX). Males inherit an X chromosome from their mother and a Y chromosome from their father (XY). This means that if a son inherits an X chromosome carrying hemophilia from his mother, he will have hemophilia. By contrast, daughters have two X chromosomes, even if they inherit the hemophilia gene from their mother, they inherit a healthy X chromosome from their father and as a result they are only carrier but not affected. | Females inherit two X chromosomes, one from their mother and one from their father (XX). Males inherit an X chromosome from their mother and a Y chromosome from their father (XY). This means that if a son inherits an X chromosome carrying hemophilia from his mother, he will have hemophilia. By contrast, daughters have two X chromosomes, even if they inherit the hemophilia gene from their mother, they inherit a healthy X chromosome from their father and as a result they are only carrier but not affected. | ||
