Apolipoprotein H

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
Identifiers
Symbol(s)	APOH; B2G1; BG
External IDs	OMIM: 138700 MGI: 88058 Homologene: 26
Gene Ontology Molecular Function: • lipid transporter activity • heparin binding Cellular Component: • extracellular region Biological Process: • defense response
RNA expression pattern
Additional recommended knowledge Correct Test Weight Handling Guide: 12 Practical Tips Daily Sensitivity Test How to quickly check pipettes? More reference expression data
Orthologs
	Human	Mouse
Entrez	350	11818
Ensembl	ENSG00000091583	ENSMUSG00000000049
Uniprot	P02749	Q6LAL7
Refseq	NM_000042 (mRNA) NP_000033 (protein)	NM_013475 (mRNA) NP_038503 (protein)
Location	Chr 17: 61.64 - 61.66 Mb	Chr 11: 108.21 - 108.23 Mb
Pubmed search	[1]	[2]

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.^[1] 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).^[2]

Apo-H has a complex involvement in agglutination, it appears to alter ADP mediated agglutenation of platlets.^[3] 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.

Inhibitory activities

Apo-H appears to completely inhibit serotonin release by the platelets^[4] 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. ^[5] 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.^[6]

Apo-H also inhibits the generation of factor Xa in the presence of platelets.^[7] Apo-H also inhibits that activation of factor XIIa.^[8]

In addition, Apo-H inhibits the activation of protein C blocking its activity on phosphatidylserine:phosphatidylcholine vesicles^[9] 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. ^[10] This inhibitory activity was diminished by adding phospholipids suggesting the Apo-H inhibition of protein C is phospholipid competitive.^[11] This indicates that under certain conditions Apo-H takes on a procoagulation properties.

Pathology

Anti-cardiolipin antibodies are found in both infectious (syphilis) and autoimmune disease(sclerosis, lupus).^[12] The activity of anti-cardiolipin antibodies in autoimmune antiphospholipid syndrome requires apolipoprotein H.^[13][14] 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.

References