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Apolipoprotein H

β2-glycoprotein 1, also known as beta-2 glycoprotein 1 and Apolipoprotein H (Apo-H), is a 38 kDa multifunctional plasma protein that in humans is encoded by the APOH gene.[5] One of its functions is to bind cardiolipin. When bound, the structure of cardiolipin and β2-GP1 both undergo large changes in structure.[6] 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).[7]

β2-GP1 has a complex involvement in agglutination. It appears to alter adenosine diphosphate (ADP)-mediated agglutination of platelets.[8] Normally, β2-GP1 assumes an anticoagulation activity in serum (by inhibiting coagulation factors); however, changes in blood factors can result in a reversal of that activity.


Although previously referred to as apolipoprotein H, it is not present in appreciable quantities in the lipoprotein fractions, so ApoH is therefore thought to be a misnomer.[9]

Inhibitory activities[edit]

β2-GP1 appears to completely inhibit serotonin release by the platelets[10] and prevents subsequent waves of the ADP-induced aggregation. The activity of β2-GP1 appears to involve the binding of agglutinating, negatively charged compounds, and inhibits agglutination by the contact activation of the intrinsic blood coagulation pathway.[11] β2-GP1 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 β2-GP1 suggesting a regulatory role of β2-GP1 in coagulation.[12]


β2-GP1 also inhibits the generation of factor Xa in the presence of platelets.[13] β2-GP1 also inhibits that activation of factor XIIa.[14]


In addition, β2-GP1 inhibits the activation of protein C blocking its activity on phosphatidylserine:phosphatidylcholine vesicles[15] 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.[16] This inhibitory activity is diminished by adding phospholipids suggesting the Apo-H inhibition of protein C is phospholipid competitive.[17] This indicates that under certain conditions Apo-H takes on procoagulation properties.

Pathology[edit]

Anti-β2-GP1 antibodies are found in both infectious and some systemic autoimmune diseases (eg. systemic lupus erythematosus (SLE)).[18] Positivity for anti-cardiolipin antibodies in diagnostic tests for autoimmune antiphospholipid syndrome requires the presence of β2-GP1in the cardiolipin extract.[19][20] Anti-β2-GP1 antibodies are strongly associated with thrombotic forms of lupus.

at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

Apolipoprotein+H

Apolipoprotein H and Applied Research

Human genome location and APOH gene details page in the UCSC Genome Browser.

APOH

provides an overview of all the structure information available in the PDB for Human Apolipoprotein H (B2G1)

PDBe-KB