Biology Reference
In-Depth Information
proteolytic enzymes of coagulation. The EGF-like domain was first recognized
among clotting proteins in factor X. Two copies of this motif are found in all the
vitamin K-dependent proteins of coagulation (factor IX, factor X, factor VII, pro-
tein C) except protein S which has four and prothrombin which has none. The
action of vitamin K in coaguloprotein synthesis is to promote carboxylation of N-
terminal glutamic acid (Gla) residues by a liver microsomal enzyme system. The
five proteins which share this N-terminal modification have a homologous
propeptide domain that functions as a signal to the carboxylase.
The organization of coagulation factor genes reflects to a considerable extent
their functional modular assembly as described above.
Figure 3.8
shows the gene
structure of several clotting factors. It is apparent that since factors VII (
F7
;
13q34), X (
F10
; 13q34), IX (
F9
; Xq26.3-q27.1) and protein C (
PROC
; 2q13-q21)
have virtually identical protein and gene structures, they must have emerged rel-
atively recently by a process of gene duplication and divergence. Similarly, tissue
plasminogen activator (
PLAT
; 8p12-q11.2), factor XI (
F11
; 4q35), factor XII
Prothrombin
Factor IX
Factor X
Factor VII
Protein C
Factor XI
Pre-kallikrein
Factor XII
Protein S
Tissue plasminogen
activator
Pro-urokinase
Plasminogen
KEY
Processing peptidase
Signal peptide
Carboxylase signal
Gla domain
Amphipathic helix
Kringle domain
Activation peptide
EGF domain
Apple domain
Serine protease
Fibronectin finger domains
Activation cleavage
Figure 3.7.
Domains of hemostatic proteins (redrawn from Tuddenham and Cooper,
1994).
