Apolipoprotein H (beta-2-glycoprotein I)
| Derived from PDB structure 1C1Z. Blue regions are positively charged and red regions are negatively charged.
| Available structures: 1c1z, 1g4f, 1g4g, 1qub
|| APOH; B2G1; BG
| External IDs
|| OMIM: 138700 MGI: 88058 Homologene: 26
| Molecular Function:
|| • lipid transporter activity|
• heparin binding
| Cellular Component:
|| • extracellular region|
| Biological Process:
|| • defense response|
| RNA expression pattern
Additional recommended knowledge
More reference expression data
|| NM_000042 (mRNA)|
|| Chr 17: 61.64 - 61.66 Mb
|| Chr 11: 108.21 - 108.23 Mb
| Pubmed search
Apolipoprotein H (Apo-H), previously known as (β2-glycoprotein I, beta-2 glycoprotein I), is a multifunctional apolipoprotein. One of its function is to bind cardiolipin. When bound the structure of cardiolipin and Apo-H both undergo large changes in structure. Within the structure of Apo-H is a stretch of positively charged amino acids, (protein sequence positions 282-287) Lys-Asn-Lys-Glu-Lys-Lys, are involved in phospholipid binding (See image on right).
Apo-H has a complex involvement in agglutination, it appears to alter ADP mediated agglutenation of platlets. Normally Apo-H assumes an anti-coagulation activity in serum (by inhibiting coagulation factors), however changes in blood factors can result of a reversal of that activity.
Apo-H appears to completely inhibit serotonin release by the platelets and prevents subsequent waves of the ADP-induced aggregation. The activity of Apo-H appears to involve the binding of agglutenating, negatively charged compounds, and inhibits agglutenation by the contact activation of the intrinsic blood coagulation pathway.  Apo-H causes a reduction of the prothrombinase binding sites on platelets and reduces the activation caused by collagen when thrombin is present at physiological serum concentrations of Apo-H suggesting a regulatory role of Apo-H in coagulation.
Apo-H also inhibits the generation of factor Xa in the presence of platelets. Apo-H also inhibits that activation of factor XIIa.
In addition, Apo-H inhibits the activation of protein C blocking its activity on phosphatidylserine:phosphatidylcholine vesicles however once protein C is activated, Apo-H fails to inhibit activity. Since protein C is involved in factor Va degradation Apo-H indirectly inhibits the degradation of factor Va.  This inhibitory activity was diminished by adding phospholipids suggesting the Apo-H inhibition of protein C is phospholipid competitive. This indicates that under certain conditions Apo-H takes on a procoagulation properties.
Anti-cardiolipin antibodies are found in both infectious (syphilis) and autoimmune disease(sclerosis, lupus). The activity of anti-cardiolipin antibodies in autoimmune antiphospholipid syndrome requires apolipoprotein H. The subset of antibodies that bind Apo-H and alter its activity are condsidered different from
antibodies that bind thrombin, serum phospholipids and are called anti-apolipoprotein antibodies. In autoimmune disease, anti-apolipoprotein antibodies (Anti β2 glycoprotein I antibodies) strongly associate with thrombitic forms of lupus and sclerosis.
- ^ Borchman D, Harris EN, Pierangeli SS, Lamba OP (1995). "Interactions and molecular structure of cardiolipin and beta 2-glycoprotein 1 (beta 2-GP1)". Clin. Exp. Immunol. 102 (2): 373-8. PMID 7586693.
- ^ Sheng Y, Sali A, Herzog H, Lahnstein J, Krilis SA (1996). "Site-directed mutagenesis of recombinant human beta 2-glycoprotein I identifies a cluster of lysine residues that are critical for phospholipid binding and anti-cardiolipin antibody activity". J. Immunol. 157 (8): 3744-51. PMID 8871678.
- ^ Nimpf J, Wurm H, Kostner GM (1985). "Interaction of beta 2-glycoprotein-I with human blood platelets: influence upon the ADP-induced aggregation". Thromb. Haemost. 54 (2): 397-401. PMID 4082080.
- ^ Nimpf J, Wurm H, Kostner GM (1987). "Beta 2-glycoprotein-I (apo-H) inhibits the release reaction of human platelets during ADP-induced aggregation". Atherosclerosis 63 (2-3): 109-14. PMID 3827975.
- ^ Schousboe I (1985). "beta 2-Glycoprotein I: a plasma inhibitor of the contact activation of the intrinsic blood coagulation pathway". Blood 66 (5): 1086-91. PMID 4052628.
- ^ Nimpf J, Bevers EM, Bomans PH, et al (1986). "Prothrombinase activity of human platelets is inhibited by beta 2-glycoprotein-I". Biochim. Biophys. Acta 884 (1): 142-9. PMID 3768409.
- ^ Shi W, Chong BH, Hogg PJ, Chesterman CN (1993). "Anticardiolipin antibodies block the inhibition by beta 2-glycoprotein I of the factor Xa generating activity of platelets". Thromb. Haemost. 70 (2): 342-5. PMID 8236146.
- ^ Schousboe I, Rasmussen MS (1995). "Synchronized inhibition of the phospholipid mediated autoactivation of factor XII in plasma by beta 2-glycoprotein I and anti-beta 2-glycoprotein I". Thromb. Haemost. 73 (5): 798-804. PMID 7482406.
- ^ Keeling DM, Wilson AJ, Mackie IJ, Isenberg DA, Machin SJ (1993). "Role of beta 2-glycoprotein I and anti-phospholipid antibodies in activation of protein C in vitro". J. Clin. Pathol. 46 (10): 908-11. PMID 8227406.
- ^ Matsuda J, Gohchi K, Kawasugi K, Gotoh M, Saitoh N, Tsukamoto M (1995). "Inhibitory activity of anti-beta 2-glycoprotein I antibody on factor Va degradation by activated-protein C and its cofactor protein S". Am. J. Hematol. 49 (1): 89-91. PMID 7741146.
- ^ Mori T, Takeya H, Nishioka J, Gabazza EC, Suzuki K (1996). "beta 2-Glycoprotein I modulates the anticoagulant activity of activated protein C on the phospholipid surface". Thromb. Haemost. 75 (1): 49-55. PMID 8713779.
- ^ Kumar KS, Jyothy A, Prakash MS, Rani HS, Reddy PP (2002). "Beta2-glycoprotein I dependent anticardiolipin antibodies and lupus anticoagulant in patients with recurrent pregnancy loss". Journal of postgraduate medicine 48 (1): 5-10. PMID 12082318.
- ^ McNeil HP, Simpson RJ, Chesterman CN, Krilis SA (1990). "Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: beta 2-glycoprotein I (apolipoprotein H)". Proc. Natl. Acad. Sci. U.S.A. 87 (11): 4120-4. PMID 2349221.
- ^ Hunt JE, McNeil HP, Morgan GJ, Crameri RM, Krilis SA (1992). "A phospholipid-beta 2-glycoprotein I complex is an antigen for anticardiolipin antibodies occurring in autoimmune disease but not with infection". Lupus 1 (2): 75-81. PMID 1301967.