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 Daily Visual Balance Check Weighing the right way Daily Sensitivity Test 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