Coagulation glycoproteins—carbohydrate composition and biological relevance
| Haemostatic glycoprotein . | N-linked sites . | O-linked sites . | Functional significance of glycan structures . | Physiological and pathological glycoforms . |
|---|---|---|---|---|
| Fibrinogen | 4 | 0 | Promotes fibrinogen solubility93 | Pathological: fibrinogens Lima,80 Caracas II,81 Niigata,94 Pontoise, Asahi,82 and Kaiserslautern95 |
| Prothrombin | 3 | 0 | None described | None described |
| TF | 3 | ND | Glycans modulate procoagulant activity of TF36 -38 | None described |
| Factor V | 26 | ND | Glycans modulate intracellular trafficking from ER to Golgi.13 ,14 N-linked glycans also influence FVa phospholipid binding affinity and FVa susceptibility to APC mediated proteolysis.58 -60 | Physiological: FVa1 and FVa2 |
| Pathological: factor V Liverpool (Ile359Thr)79 | ||||
| Factor VII | 2 | 2 | Influence hepatic clearance and plasma half-life of recombinant FVIIa. Loss of O-linked glycans impairs procoagulant activity of FVIIa in plasma.96 | None described |
| Factor VIII | 24 | 7 | Glycans influence FVIII folding and intracellular trafficking during biosynthesis.13 ,14 N-linked glycans also regulate FVIII uptake by dendritic cells91 ,97 and clearance by the ASGPR. | Pathological: factor VIII (Met1772Thr) and (Ile566Thr) 25 |
| Factor IX | 2 | 5 | None described | Pathological: factor IX (Arg94Ser) 83 |
| Factor X | 2 | 2 | Both N- and O-linked glycans are negative modulators of FX zymogen activation.42 N-linked glycans also regulate FX clearance.45 | None described |
| Factor XI | 5 | ND | None described | None described |
| Factor XII | 2 | 7 | None described | None described |
| Factor XIII | 3 | ND | None described | None described |
| VWF | 12 | 10 | N-linked and O-linked glycans influence VWF synthesis, secretion, and biological activity.27 ,35 ,98 Glycan expression also regulates susceptibility to ADAMTS13 proteolysis34 and is a critical determinant of VWF clearance.67 | Physiological: ABO blood group–specific glycoforms |
| PC | 4 | 0 | Modulate PC zymogen activation by thrombin thrombomodulin complex.54 Glycans also influence the anticoagulant and antiinflammatory properties of APC.55 | Physiological: α-protein C, β-protein C, γ- protein C53 |
| Protein S | 3 | ND | None described | Pathological: protein S Heerlen (Ser460Pro) 84 |
| Antithrombin | 4 | 0 | Glycans influence conformational changes in antithrombin after heparin binding, and thereby regulate serpin activity.47 ,51 | Physiological: α-antithrombin and β-antithrombin47 |
| Pathological: antithrombin (Ile7Asn),99 antithrombin (Ser82Asn) 100 |
| Haemostatic glycoprotein . | N-linked sites . | O-linked sites . | Functional significance of glycan structures . | Physiological and pathological glycoforms . |
|---|---|---|---|---|
| Fibrinogen | 4 | 0 | Promotes fibrinogen solubility93 | Pathological: fibrinogens Lima,80 Caracas II,81 Niigata,94 Pontoise, Asahi,82 and Kaiserslautern95 |
| Prothrombin | 3 | 0 | None described | None described |
| TF | 3 | ND | Glycans modulate procoagulant activity of TF36 -38 | None described |
| Factor V | 26 | ND | Glycans modulate intracellular trafficking from ER to Golgi.13 ,14 N-linked glycans also influence FVa phospholipid binding affinity and FVa susceptibility to APC mediated proteolysis.58 -60 | Physiological: FVa1 and FVa2 |
| Pathological: factor V Liverpool (Ile359Thr)79 | ||||
| Factor VII | 2 | 2 | Influence hepatic clearance and plasma half-life of recombinant FVIIa. Loss of O-linked glycans impairs procoagulant activity of FVIIa in plasma.96 | None described |
| Factor VIII | 24 | 7 | Glycans influence FVIII folding and intracellular trafficking during biosynthesis.13 ,14 N-linked glycans also regulate FVIII uptake by dendritic cells91 ,97 and clearance by the ASGPR. | Pathological: factor VIII (Met1772Thr) and (Ile566Thr) 25 |
| Factor IX | 2 | 5 | None described | Pathological: factor IX (Arg94Ser) 83 |
| Factor X | 2 | 2 | Both N- and O-linked glycans are negative modulators of FX zymogen activation.42 N-linked glycans also regulate FX clearance.45 | None described |
| Factor XI | 5 | ND | None described | None described |
| Factor XII | 2 | 7 | None described | None described |
| Factor XIII | 3 | ND | None described | None described |
| VWF | 12 | 10 | N-linked and O-linked glycans influence VWF synthesis, secretion, and biological activity.27 ,35 ,98 Glycan expression also regulates susceptibility to ADAMTS13 proteolysis34 and is a critical determinant of VWF clearance.67 | Physiological: ABO blood group–specific glycoforms |
| PC | 4 | 0 | Modulate PC zymogen activation by thrombin thrombomodulin complex.54 Glycans also influence the anticoagulant and antiinflammatory properties of APC.55 | Physiological: α-protein C, β-protein C, γ- protein C53 |
| Protein S | 3 | ND | None described | Pathological: protein S Heerlen (Ser460Pro) 84 |
| Antithrombin | 4 | 0 | Glycans influence conformational changes in antithrombin after heparin binding, and thereby regulate serpin activity.47 ,51 | Physiological: α-antithrombin and β-antithrombin47 |
| Pathological: antithrombin (Ile7Asn),99 antithrombin (Ser82Asn) 100 |
ND, not determined.