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Until now only twelve human
Gla-proteins have been discovered and characterized to the level
of primary structure:
| Gla
proteins |
Abbreviation |
Tissue |
Function |
| Prothrombin |
FII |
liver
– plasma |
procoagulant |
| Factor
VII |
FVII |
liver
– plasma |
procoagulant |
| Factor
IX |
FIX |
liver
– plasma |
procoagulant |
| Factor
X |
FX |
liver
– plasma |
procoagulant |
| Protein
C |
|
liver
– plasma |
anticoagulant |
| Protein
S |
|
liver
– plasma |
anticoagulant |
| Protein
Z |
|
liver
– plasma |
anticoagulant |
| Osteocalcin |
OC
/ BGP |
bone
- dentin |
regulator
of crystallization |
| Matrix
Gla Protein |
MGP |
cartilage
– vessel wall |
inhibitor
of ectopic calcification |
| Growth
arrest specific gene-6 protein |
gas6 |
most
soft tissues |
regulator
of cell growth |
| Proline-rich
Gla proteins |
PRGP |
most
soft tissues |
unknown |
| Transmembrane
Gla proteins |
TMG |
most
soft tissues |
unknown |
| |
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|
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In
all cases in which their function was known, the presence of the
Gla-residues in these proteins turned out to be essential for functional
activity.
Gla-proteins
occur in a wide variety of vertebrates: mammals, birds, reptiles,
and fish. A number of Australian snakes have been discovered the
venom of which acts by activating the human blood clotting system.
Remarkably, in some cases activation was accomplished by Gla-proteins
capable of binding to phospholipid membranes and subsequent conversion
of procoagulant clotting factors into activated ones.
Another
interesting class of invertebrate Gla-proteins is formed by the
conantokins, produced by the fish-hunting snail Conus Geographus.
These snails produce a neurotoxin containing a variety of extremely
Gla-rich proteins, which are sufficiently powerful to kill an adult
man.
Recommended
literature:
- Tans,
G., Govers-Riemslag, J.W., van Rijn, J.L., Rosing, J. (1985).
Purification and properties
of a prothrombin activator from the venom of Notechis scutatus
scutatus J. Biol. Chem. 260, 9366-9372.
- Speijer,
H., Govers-Riemslag, J.W., Zwaal, R.F.A., Rosing, J. (1986).
Prothrombin activation by
an activator from the venom of Oxyuranus scutellatus (Taipan
snake). J. Biol. Chem. 261, 13258-13567.
- Olivera, B.M., Gray, W.R., Zeikus, R., McIntosh,
J.M., Varga, J., Rivier, J., de Santos, V., Cruz, L.J. (1985)
Peptide neurotoxins from fish-hunting cone snails. Science 230,
1338-1343.
- Furie, B., Bouchard, B.A., Furie, B.C. (1999).
Vitamin K-dependent biosynthesis of gammacarboxy glutamic acid.
Blood 93, 1798-1808.
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