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Gene Review

APOH  -  apolipoprotein H (beta-2-glycoprotein I)

Homo sapiens

Synonyms: APC inhibitor, Activated protein C-binding protein, Anticardiolipin cofactor, Apo-H, Apolipoprotein H, ...
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Disease relevance of APOH


High impact information on APOH


Chemical compound and disease context of APOH


Biological context of APOH


Anatomical context of APOH

  • To confirm whether these are functional mutations, we mutagenized APOH cDNAs and transiently expressed them in COS-1 cells [20].
  • We have recently found that CD4(+) T cells autoreactive to beta(2)GPI in patients with APS preferentially recognize a cryptic peptide encompassing amino acid residues 276-290 (p276-290), which contains the major PL-binding site, in the context of DR53 [2].
  • In addition, the p276-290-reactive T-cell response was primed by stimulating peripheral blood T cells from DR53-carrying healthy individuals with dendritic cells bearing PL-bound beta(2)GPI in vitro [2].
  • However, it is not clear how previously cryptic p276-290 becomes visible to the immune system and elicits a pathogenics autoimmune response to beta(2)GPI [2].
  • Dendritic cells or macrophages pulsed with PL-bound beta(2)GPI induced a response of p276-290-specific CD4(+) T-cell lines generated from the patients in an HLA-DR-restricted and antigen-processing-dependent manner but those with beta(2)GPI or PL alone did not [2].

Associations of APOH with chemical compounds


Physical interactions of APOH

  • The binding of beta2-glycoprotein-I and beta2-glycoprotein-I- phospholipid complexes to megalin was completely blocked by receptor-associated protein [7].
  • It has been shown that APOH has structural similarities with the regulation of complement activation (RCA) protein superfamily and is involved in phospholipid binding interactions on platelets and as an autoantigen in complex with anionic phospholipids [18].
  • DeltaV did not associate with apoER2'. We conclude that domain V is involved in both binding beta(2)GPI to anionic PL and in interaction with apoER2' and subsequent activation of platelets [25].
  • These results demonstrate that annexin II mediates the binding of beta(2)GPI to endothelial cells [26].
  • It is the main target antigen for antiphospholipid antibodies in patients with antiphospholipid syndrome (APS). beta(2)GPI binds with high affinity to the atherogenic lipoprotein Lp(a) which shares structural homology with plasminogen, a key molecule in the fibrinolytic system [27].

Regulatory relationships of APOH

  • Moreover, a specific p38 MAPK inihibitor SB203580 decreased aCL/beta(2)GPI-induced TF mRNA expression [28].
  • IgG anti-beta(2)GPI antibodies recognized the beta(2)GPI at the endothelial surface inducing its activation with an increase of ICAM-I and a decrease in the expression of thrombomodulin favoring a pro-thrombotic state in the vascular endothelium [27].
  • METHODS: Sixty-five Japanese patients with APS and/or systemic lupus erythematosus who were positive for antiphospholipid antibodies and 61 controls were analyzed for the presence of the Val/Leu(247) polymorphism of beta(2)GPI [10].
  • Plk1 regulates activation of the anaphase promoting complex by phosphorylating and triggering SCFbetaTrCP-dependent destruction of the APC Inhibitor Emi1 [29].

Other interactions of APOH

  • In addition to APOE the gene products of five other apolipoprotein loci were screened and low frequency variation, possibly due to European admixture, was observed in two systems (APOH and APOA-IV) [30].
  • The binding site in beta(2)GPI for interaction with apoER2' does not overlap with the hydrophobic insertion loop in domain V [25].
  • Finally, surface plasmon resonance studies revealed high affinity binding between annexin II and beta(2)GPI [26].
  • We hypothesize that LBA/CHS1/BG proteins function in polarized vesicle trafficking by guiding intracellular vesicles to activated receptor complexes and thus facilitate polarized secretion and/or membrane deposition of immune effector molecules [31].
  • Thus, aCL/beta(2)GPI plays dual roles in the pathogenesis of APS, firstly by deranging the fibrinolytic system and secondly by activating monocytes, endothelial cells and thrombocytes to produce TF or thromboxane [28].

Analytical, diagnostic and therapeutic context of APOH


  1. Complete DNA sequence variation in the apolipoprotein H (beta-glycoprotein I) gene and identification of informative SNPs. Chen, Q., Kamboh, M.I. Ann. Hum. Genet. (2006) [Pubmed]
  2. Binding of beta 2-glycoprotein I to anionic phospholipids facilitates processing and presentation of a cryptic epitope that activates pathogenic autoreactive T cells. Kuwana, M., Matsuura, E., Kobayashi, K., Okazaki, Y., Kaburaki, J., Ikeda, Y., Kawakami, Y. Blood (2005) [Pubmed]
  3. Valine/valine genotype at position 247 of the beta2-glycoprotein I gene in Mexican patients with primary antiphospholipid syndrome: association with anti-beta2-glycoprotein I antibodies. Prieto, G.A., Cabral, A.R., Zapata-Zuñiga, M., Simón, A.J., Villa, A.R., Alarcón-Segovia, D., Cabiedes, J. Arthritis Rheum. (2003) [Pubmed]
  4. Hepatitis B virus surface antigen binds to apolipoprotein H. Mehdi, H., Kaplan, M.J., Anlar, F.Y., Yang, X., Bayer, R., Sutherland, K., Peeples, M.E. J. Virol. (1994) [Pubmed]
  5. Nucleotide sequence and expression of the human gene encoding apolipoprotein H (beta 2-glycoprotein I). Mehdi, H., Nunn, M., Steel, D.M., Whitehead, A.S., Perez, M., Walker, L., Peeples, M.E. Gene (1991) [Pubmed]
  6. Bacterial induction of autoantibodies to beta2-glycoprotein-I accounts for the infectious etiology of antiphospholipid syndrome. Blank, M., Krause, I., Fridkin, M., Keller, N., Kopolovic, J., Goldberg, I., Tobar, A., Shoenfeld, Y. J. Clin. Invest. (2002) [Pubmed]
  7. beta2-glycoprotein-I (apolipoprotein H) and beta2-glycoprotein-I-phospholipid complex harbor a recognition site for the endocytic receptor megalin. Moestrup, S.K., Schousboe, I., Jacobsen, C., Leheste, J.R., Christensen, E.I., Willnow, T.E. J. Clin. Invest. (1998) [Pubmed]
  8. Inhibition of activated protein C by platelets. Jane, S.M., Mitchell, C.A., Hau, L., Salem, H.H. J. Clin. Invest. (1989) [Pubmed]
  9. Action of anticardiolipin and antibodies to beta2-glycoprotein-I on trophoblast proliferation as a mechanism for fetal death. Chamley, L.W., Duncalf, A.M., Mitchell, M.D., Johnson, P.M. Lancet (1998) [Pubmed]
  10. Significance of valine/leucine247 polymorphism of beta2-glycoprotein I in antiphospholipid syndrome: increased reactivity of anti-beta2-glycoprotein I autoantibodies to the valine247 beta2-glycoprotein I variant. Yasuda, S., Atsumi, T., Matsuura, E., Kaihara, K., Yamamoto, D., Ichikawa, K., Koike, T. Arthritis Rheum. (2005) [Pubmed]
  11. An Endogenous Inhibitor of Angiogenesis derived from a Transitional Cell Carcinoma: Clipped beta2-Glycoprotein-I. Beecken, W.D., Engl, T., Ringel, E.M., Camphausen, K., Michaelis, M., Jonas, D., Folkman, J., Shing, Y., Blaheta, R.A. Ann. Surg. Oncol. (2006) [Pubmed]
  12. Serum anti-beta2-glycoprotein-I and anticardiolipin antibodies during thrombosis in systemic lupus erythematosus patients. Gómez-Pacheco, L., Villa, A.R., Drenkard, C., Cabiedes, J., Cabral, A.R., Alarcón-Segovia, D. Am. J. Med. (1999) [Pubmed]
  13. beta 2 glycoprotein-I inhibits factor XII activation on triglyceride rich lipoproteins: the effect of antibodies from plasma of patients with antiphospholipid syndrome. McNally, T., Mackie, I.J., Isenberg, D.A., Machin, S.J. Thromb. Haemost. (1996) [Pubmed]
  14. Antibodies to beta 2-glycoprotein-I: urea resistance, binding specificity, and association with thrombosis. Vlachoyiannopoulos, P.G., Petrovas, C., Tektonidou, M., Krilis, S., Moutsopoulos, H.M. J. Clin. Immunol. (1998) [Pubmed]
  15. Molecular basis of the apolipoprotein H (beta 2-glycoprotein I) protein polymorphism. Sanghera, D.K., Kristensen, T., Hamman, R.F., Kamboh, M.I. Hum. Genet. (1997) [Pubmed]
  16. Human beta 2-glycoprotein I: molecular analysis of DNA and amino acid polymorphism. Steinkasserer, A., Dörner, C., Würzner, R., Sim, R.B. Hum. Genet. (1993) [Pubmed]
  17. Apolipoprotein E and H polymorphisms in Mongolian Buryat: allele frequencies and relationship with plasma lipid levels. Tsunoda, K., Harihara, S., Dashnyam, B., Semjidmaa, D., Yamaguchi, Y., Tanabe, Y., Sakai, N., Sato, A., Sato, K. Hum. Biol. (2002) [Pubmed]
  18. Assignment of apolipoprotein H (APOH: beta-2-glycoprotein I) to human chromosome 17q23----qter; determination of the major expression site. Steinkasserer, A., Cockburn, D.J., Black, D.M., Boyd, Y., Solomon, E., Sim, R.B. Cytogenet. Cell Genet. (1992) [Pubmed]
  19. Apolipoprotein H genetic variability in the population of Krk Island, Croatia. Vitale, K., Trbojević-Cepe, M., Smolej-Narancić, N. Hum. Biol. (2002) [Pubmed]
  20. A hydrophobic sequence at position 313-316 (Leu-Ala-Phe-Trp) in the fifth domain of apolipoprotein H (beta2-glycoprotein I) is crucial for cardiolipin binding. Mehdi, H., Naqvi, A., Kamboh, M.I. Eur. J. Biochem. (2000) [Pubmed]
  21. Genetic association of five apolipoprotein polymorphisms with serum lipoprotein-lipid levels in African blacks. Kamboh, M.I., Bunker, C.H., Aston, C.E., Nestlerode, C.S., McAllister, A.E., Ukoli, F.A. Genet. Epidemiol. (1999) [Pubmed]
  22. Genetic variation in the apolipoprotein H (beta2-glycoprotein I) gene affects plasma apolipoprotein H concentrations. Mehdi, H., Aston, C.E., Sanghera, D.K., Hamman, R.F., Kamboh, M.I. Hum. Genet. (1999) [Pubmed]
  23. Apolipoprotein H (beta-2-glycoprotein I) polymorphism in Asians. Saha, N., Kamboh, M.I., Kelly, L.J., Ferrell, R.E., Tay, J.S. Hum. Biol. (1992) [Pubmed]
  24. Solution structure of human and bovine beta(2)-glycoprotein I revealed by small-angle X-ray scattering. Hammel, M., Kriechbaum, M., Gries, A., Kostner, G.M., Laggner, P., Prassl, R. J. Mol. Biol. (2002) [Pubmed]
  25. The binding site in {beta}2-glycoprotein I for ApoER2' on platelets is located in domain V. van Lummel, M., Pennings, M.T., Derksen, R.H., Urbanus, R.T., Lutters, B.C., Kaldenhoven, N., de Groot, P.G. J. Biol. Chem. (2005) [Pubmed]
  26. High affinity binding of beta 2-glycoprotein I to human endothelial cells is mediated by annexin II. Ma, K., Simantov, R., Zhang, J.C., Silverstein, R., Hajjar, K.A., McCrae, K.R. J. Biol. Chem. (2000) [Pubmed]
  27. The role of beta2-glycoprotein I (beta(2)GPI) in the activation of plasminogen. López-Lira, F., Rosales-León, L., Martínez, V.M., Ruiz Ordaz, B.H. Biochim. Biophys. Acta (2006) [Pubmed]
  28. Pathogenesis of antiphospholipid antibodies: impairment of fibrinolysis and monocyte activation via the p38 mitogen-activated protein kinase pathway. Yasuda, S., Bohgaki, M., Atsumi, T., Koike, T. Immunobiology (2005) [Pubmed]
  29. Plk1 regulates activation of the anaphase promoting complex by phosphorylating and triggering SCFbetaTrCP-dependent destruction of the APC Inhibitor Emi1. Hansen, D.V., Loktev, A.V., Ban, K.H., Jackson, P.K. Mol. Biol. Cell (2004) [Pubmed]
  30. Genetic studies of human apolipoproteins. XVI. APOE polymorphism and cholesterol levels in the Mayans of the Yucatan Peninsula, Mexico. Kamboh, M.I., Weiss, K.M., Ferrell, R.E. Clin. Genet. (1991) [Pubmed]
  31. Identification of a novel lipopolysaccharide-inducible gene with key features of both A kinase anchor proteins and chs1/beige proteins. Wang, J.W., Howson, J., Haller, E., Kerr, W.G. J. Immunol. (2001) [Pubmed]
  32. Genetic polymorphisms of apolipoproteins A-IV, E and H in Koreans. Kim, H.S., Kamboh, M.I. Hum. Hered. (1998) [Pubmed]
  33. Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: beta 2-glycoprotein I (apolipoprotein H). McNeil, H.P., Simpson, R.J., Chesterman, C.N., Krilis, S.A. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
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