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. One of its functions is to bind cardiolipin. When bound the structure of cardiolipin and β2-GP1 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).
β2-GP1 has a complex involvement in agglutination, it appears to alter adenosine diphosphate (ADP) mediated agglutination of platelets. Normally β2-GP1 assumes an anti-coagulation activity in serum (by inhibiting coagulation factors); however, changes in blood factors can result of a reversal of that activity.
β2-GP1 appears to completely inhibit serotonin release by the platelets 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. 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.
In addition, β2-GP1 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-β2-GP1 antibodies are found in both infectious and some systemic autoimmune diseases (eg. systemic lupus erythematosus (SLE)). Positivity for anti-cardiolipin antibodies in diagnostic tests for autoimmune antiphospholipid syndrome requires the presence of β2-GP1in the cardiolipin extract. Anti β2-GP1 antibodies strongly associate with thrombotic forms of lupus.
Sushi 2 protein domain
NMR structure of the fifth domain of human beta-2-glycoprotein I
In molecular biology, the protein domain Sushi 2 is also known as the fifth protein domain of beta-2-glycoprotein-1 (β2-GP1). This protein domain is only found in eukaryotes. The first four domains found in Apolipoprotein H resemble each other, however the fifth one appears to be different.
This protein domain is composed of four well-defined anti-parallel beta-strands and two short alpha-helices, as well as a long highly flexible loop. Additionally, the fifth protein domain appears to resemble the other four in Apolipoprotein with the exception of three internal disulfide bonds and an extra C-terminal loop.
Its exact function remains to be fully elucidated; however it is known to play an important role in the binding of β2-GP1 to negatively charged compounds and subsequent capture for binding of anti-β2-GP1 antibodies. Development of antibodies against β2-GP1 can lead to Antiphospholipid syndrome which often leads to pregnancy complications.
- GRCh38: Ensembl release 89: ENSG00000091583 - Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000000049 - Ensembl, May 2017
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- Apolipoprotein+H at the US National Library of Medicine Medical Subject Headings (MeSH)
- Apolipoprotein H and Applied Research
- Human APOH genome location and APOH gene details page in the UCSC Genome Browser.
- PDBe-KB provides an overview of all the structure information available in the PDB for Human Apolipoprotein H (B2G1)