Apolipoprotein H

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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
RNA expression pattern

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.

Contents

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

  1. ↑ Borchman D, Harris EN, Pierangeli SS, Lamba OP (1995). "Interactions and molecular structure of cardiolipin and beta 2-glycoprotein 1 (beta 2-GP1)". Clin. Exp. Immunol. 102 (2): 373-8. PMID 7586693.
  2. ↑ Sheng Y, Sali A, Herzog H, Lahnstein J, Krilis SA (1996). "Site-directed mutagenesis of recombinant human beta 2-glycoprotein I identifies a cluster of lysine residues that are critical for phospholipid binding and anti-cardiolipin antibody activity". J. Immunol. 157 (8): 3744-51. PMID 8871678.
  3. ↑ Nimpf J, Wurm H, Kostner GM (1985). "Interaction of beta 2-glycoprotein-I with human blood platelets: influence upon the ADP-induced aggregation". Thromb. Haemost. 54 (2): 397-401. PMID 4082080.
  4. ↑ Nimpf J, Wurm H, Kostner GM (1987). "Beta 2-glycoprotein-I (apo-H) inhibits the release reaction of human platelets during ADP-induced aggregation". Atherosclerosis 63 (2-3): 109-14. PMID 3827975.
  5. ↑ Schousboe I (1985). "beta 2-Glycoprotein I: a plasma inhibitor of the contact activation of the intrinsic blood coagulation pathway". Blood 66 (5): 1086-91. PMID 4052628.
  6. ↑ Nimpf J, Bevers EM, Bomans PH, et al (1986). "Prothrombinase activity of human platelets is inhibited by beta 2-glycoprotein-I". Biochim. Biophys. Acta 884 (1): 142-9. PMID 3768409.
  7. ↑ Shi W, Chong BH, Hogg PJ, Chesterman CN (1993). "Anticardiolipin antibodies block the inhibition by beta 2-glycoprotein I of the factor Xa generating activity of platelets". Thromb. Haemost. 70 (2): 342-5. PMID 8236146.
  8. ↑ Schousboe I, Rasmussen MS (1995). "Synchronized inhibition of the phospholipid mediated autoactivation of factor XII in plasma by beta 2-glycoprotein I and anti-beta 2-glycoprotein I". Thromb. Haemost. 73 (5): 798-804. PMID 7482406.
  9. ↑ Keeling DM, Wilson AJ, Mackie IJ, Isenberg DA, Machin SJ (1993). "Role of beta 2-glycoprotein I and anti-phospholipid antibodies in activation of protein C in vitro". J. Clin. Pathol. 46 (10): 908-11. PMID 8227406.
  10. ↑ Matsuda J, Gohchi K, Kawasugi K, Gotoh M, Saitoh N, Tsukamoto M (1995). "Inhibitory activity of anti-beta 2-glycoprotein I antibody on factor Va degradation by activated-protein C and its cofactor protein S". Am. J. Hematol. 49 (1): 89-91. PMID 7741146.
  11. ↑ Mori T, Takeya H, Nishioka J, Gabazza EC, Suzuki K (1996). "beta 2-Glycoprotein I modulates the anticoagulant activity of activated protein C on the phospholipid surface". Thromb. Haemost. 75 (1): 49-55. PMID 8713779.
  12. ↑ Kumar KS, Jyothy A, Prakash MS, Rani HS, Reddy PP (2002). "Beta2-glycoprotein I dependent anticardiolipin antibodies and lupus anticoagulant in patients with recurrent pregnancy loss". Journal of postgraduate medicine 48 (1): 5-10. PMID 12082318.
  13. ↑ McNeil HP, Simpson RJ, Chesterman CN, Krilis SA (1990). "Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: beta 2-glycoprotein I (apolipoprotein H)". Proc. Natl. Acad. Sci. U.S.A. 87 (11): 4120-4. PMID 2349221.
  14. ↑ Hunt JE, McNeil HP, Morgan GJ, Crameri RM, Krilis SA (1992). "A phospholipid-beta 2-glycoprotein I complex is an antigen for anticardiolipin antibodies occurring in autoimmune disease but not with infection". Lupus 1 (2): 75-81. PMID 1301967.

External links

v • d • e
Antigens: Autoantigens
Acetylcholine receptor - Actin - Apolipoprotein H - Branched-chain alpha-keto acid dehydrogenase complex - Cardiolipin - Centromere - Epidermal transglutaminase - gangliosides - Oxoglutarate dehydrogenase - Sp100 nuclear antigen - Pyruvate dehydrogenase - Thrombin - Tissue transglutaminase - Topoisomerase - Nucleoporins (Nucleoporin-62 - Nucleoporin-210)
v • d • e
Lipids: lipoprotein metabolism
GeneralChylomicron - HDL - LDL - IDL - VLDL - Lp(a)
ApolipoproteinsAPOA (1, 2, 5) - APOB - APOC (1, 2, 3, 4) - APOD - APOE - APOH
OtherLipoprotein lipase - HDL (Cholesterylester transfer proteinAcetyl-CoA C-acyltransferase, LCAT) - LDL receptor - Microsomal triglyceride transfer protein - ABCA1 - Lecithin-cholesterol acyltransferase
see also disorders
v • d • e
Protein: glycoproteins
Activin - ADAM protein - Alpha 1-antichymotrypsin - Apolipoprotein H - CD70 - Asialoglycoprotein - Avidin - B-cell activating factor - 4-1BB ligand - Cholesterylester transfer protein - Clusterin - Colony-stimulating factor - Haemopexin - Inhibin - Lactoferrin - Membrane glycoproteins - Mucoprotein - Myelin protein zero - Osteonectin - Protein C - Protein S - Proteoglycan - Serum Amyloid P component - Sialoglycoprotein (CD43, Glycophorin, Glycophorin C) - Thrombopoietin - Thyroglobulin - Thyroxine-binding proteins - Transcortin - Tumor necrosis factor-alpha - Uteroglobin - Vitronectin

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Acknowledgement and Attribution Regarding Sources of Content

Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .

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