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 PDB Ortholog search: PDBe, RCSB List of PDB id codes 1C1Z, 1G4F, 1G4G, 1QUB, 2KRI, 3OP8, 4JHS
Identifiers
Symbols	APOH ; B2G1; B2GP1; BG
External IDs	OMIM: 138700 MGI: 88058 HomoloGene: 26 ChEMBL: 2859 GeneCards: APOH Gene
Gene ontology Molecular function • glycoprotein binding • protein binding • phospholipid binding • heparin binding • lipid binding • identical protein binding • lipoprotein lipase activator activity Cellular component • extracellular space • cell surface • extracellular matrix • very-low-density lipoprotein particle • high-density lipoprotein particle • chylomicron • extracellular exosome Biological process • negative regulation of endothelial cell proliferation • triglyceride metabolic process • blood coagulation, intrinsic pathway • negative regulation of endothelial cell migration • negative regulation of angiogenesis • positive regulation of blood coagulation • negative regulation of blood coagulation • organ regeneration • plasminogen activation • negative regulation of myeloid cell apoptotic process • triglyceride transport • negative regulation of smooth muscle cell apoptotic process • positive regulation of lipoprotein lipase activity • regulation of fibrinolysis • negative regulation of fibrinolysis Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	350	11818
Ensembl	ENSG00000091583	ENSMUSG00000000049
UniProt	P02749	Q01339
RefSeq (mRNA)	NM_000042	NM_013475
RefSeq (protein)	NP_000033	NP_038503
Location (UCSC)	Chr 17: 66.21 – 66.26 Mb	Chr 11: 108.34 – 108.41 Mb
PubMed search	[1]	[2]

Apolipoprotein H (Apo-H), previously known as (β₂-glycoprotein I, beta-2 glycoprotein I), is a multifunctional apolipoprotein that in humans is encoded by the APOH gene. One of its functions 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 agglutination of platelets. 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 and prevents subsequent waves of the ADP-induced aggregation. The activity of Apo-H appears to involve the binding of agglutinating, negatively charged compounds, and inhibits agglutination 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.

Pathology

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 considered 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 thrombotic forms of lupus and sclerosis.

Sushi 2 protein domain

Sushi_2
NMR structure of the fifth domain of human beta-2-glycoprotein I
Identifiers
Symbol	Sushi_2
Pfam	PF09014
InterPro	IPR015104
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

In molecular biology, the protein domain Sushi 2 is also known as the fifth protein domain of beta-2-glycoprotein-1 (b2GP-1). 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.

Structure

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.

Function

Its exact function remains to be fully elucidated, however it is known to play an important role in the binding of b2GP-1 to negatively charged compounds and subsequent capture for binding of anti-b2GP-1 antibodies. Problems such as a mutation in this protein would lead to Antiphospholipid syndrome which often leads to pregnancy complications.

External links

• Apolipoprotein H at the US National Library of Medicine Medical Subject Headings (MeSH)
• Apolipoprotein H and Applied Research