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Gene Review

HEBP1  -  heme binding protein 1

Homo sapiens

Synonyms: HBP, HEBP, Heme-binding protein 1, p22HBP
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Disease relevance of HEBP1

  • HasA is an extracellular heme binding protein, and HasR is an outer membrane receptor protein from Serratia marcescens [1].
  • Analysis of tissue biopsies from patients with necrotizing fasciitis revealed recruitment of neutrophils and monocytes to the infectious site, combined with the release of HBP [2].
  • The results show that M protein, in synergy with HBP, evokes an inflammatory response that may contribute to the profound pathophysiological consequences seen in severe streptococcal infections [2].
  • We conclude that discontinuation rates are unacceptably high, that interventions must be continued throughout treatment, and that HBP has limited utility as an indicator chronic disease [3].
  • These results indicate that the V3 loop of HIV-1 gp120 shares an epitope with HBP [4].

High impact information on HEBP1


Chemical compound and disease context of HEBP1


Biological context of HEBP1


Anatomical context of HEBP1

  • Complex formation with hemopexin, the high-affinity heme-binding protein in plasma and cerebrospinal fluid, dampens these effects and is suggested to facilitate cellular heme metabolism [19].
  • Cultured Hodgkin's cells, as purified HBP, agglutinate T-lymphocytes expressing hyposialylated membrane glycosyl determinants [20].
  • We have previously demonstrated that HBP is internalized in monocytes [16].
  • The blood-sucking insect Rhodnius prolixus has a heme-binding protein (RHBP) in its hemolymph (Oliveira, P.L., Kawooya, J.K., Ribeiro, J.M.C., Meyer, T., Poorman, R., Alves, E.W., Walker, F., Padovan, G.J., and Masuda, H [17].
  • It is concluded that this protein, designated the hexokinase-binding protein (HBP), is an integral membrane protein responsible for the selective binding of hexokinase by the outer mitochondrial membrane [21].

Associations of HEBP1 with chemical compounds

  • In contrast to murine SOUL, which binds one heme per subunit via coordination of the Fe(III)-heme to a histidine, murine p22HBP binds one heme molecule per subunit with no specific axial ligand coordination of the Fe(III)-heme [22].
  • In addition, HBP had an additive effect on LPS-induced production of TNF-alpha and PGE2, suggesting a generalized monocyte activation [23].
  • Using isolated human monocytes and ELISA, we found that colchicine (0.1 mM), cytochalasin D (30 and 300 microM), NH4Cl (30 mM), and bafilomycin A1 (1 microM) significantly reduced the effect of HBP (10 microg/ml) to enhance LPS (10 ng/ml)-induced TNF-alpha release after 24 h [16].
  • We demonstrate that the binding of the neutrophil-derived protein HBP to monocytes is inhibited in the presence of EDTA and fucoidan [24].
  • High density lipoprotein binding protein, HBP (vigilin), which lacks a transmembrane domain is responsive to cell cholesterol levels, but its physiological significance remains unknown [25].

Physical interactions of HEBP1


Other interactions of HEBP1


Analytical, diagnostic and therapeutic context of HEBP1


  1. The heme transfer from the soluble HasA hemophore to its membrane-bound receptor HasR is driven by protein-protein interaction from a high to a lower affinity binding site. Izadi-Pruneyre, N., Huché, F., Lukat-Rodgers, G.S., Lecroisey, A., Gilli, R., Rodgers, K.R., Wandersman, C., Delepelaire, P. J. Biol. Chem. (2006) [Pubmed]
  2. Streptococcal M protein: a multipotent and powerful inducer of inflammation. Påhlman, L.I., Mörgelin, M., Eckert, J., Johansson, L., Russell, W., Riesbeck, K., Soehnlein, O., Lindbom, L., Norrby-Teglund, A., Schumann, R.R., Björck, L., Herwald, H. J. Immunol. (2006) [Pubmed]
  3. Hypertension continuation adherence: natural history and role as an indicator condition. Rudd, P., Tul, V., Brown, K., Davidson, S.M., Bostwick, G.J. Arch. Intern. Med. (1979) [Pubmed]
  4. Molecular mimicry between the human immunodeficiency virus type 1 gp120 V3 loop and human brain proteins. Trujillo, J.R., McLane, M.F., Lee, T.H., Essex, M. J. Virol. (1993) [Pubmed]
  5. Heparin-binding protein (HBP/CAP37): a missing link in neutrophil-evoked alteration of vascular permeability. Gautam, N., Olofsson, A.M., Herwald, H., Iversen, L.F., Lundgren-Akerlund, E., Hedqvist, P., Arfors, K.E., Flodgaard, H., Lindbom, L. Nat. Med. (2001) [Pubmed]
  6. Tick histamine-binding proteins: isolation, cloning, and three-dimensional structure. Paesen, G.C., Adams, P.L., Harlos, K., Nuttall, P.A., Stuart, D.I. Mol. Cell (1999) [Pubmed]
  7. Characterization of NADPH-dependent methemoglobin reductase as a heme-binding protein present in erythrocytes and liver. Xu, F., Quandt, K.S., Hultquist, D.E. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  8. Complete amino acid sequence of human hemopexin, the heme-binding protein of serum. Takahashi, N., Takahashi, Y., Putnam, F.W. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  9. A genome-wide scan for coronary heart disease suggests in Indo-Mauritians a susceptibility locus on chromosome 16p13 and replicates linkage with the metabolic syndrome on 3q27. Francke, S., Manraj, M., Lacquemant, C., Lecoeur, C., Leprêtre, F., Passa, P., Hebe, A., Corset, L., Yan, S.L., Lahmidi, S., Jankee, S., Gunness, T.K., Ramjuttun, U.S., Balgobin, V., Dina, C., Froguel, P. Hum. Mol. Genet. (2001) [Pubmed]
  10. Pindolol and systolic time intervals in patients with hypertension. Hammond, J.J., Kirkendall, W.M., Jacks-Nagle, V.L., Plotnick, G.D., Fisher, M.L., Hamilton, J.H., Robinson, M., Carliner, N.H., Janoski, A.H., Hamilton, B.P. Am. Heart J. (1982) [Pubmed]
  11. The bedtime administration of doxazosin controls morning hypertension and albuminuria in patients with type-2 diabetes: evaluation using home-based blood pressure measurements. Kamoi, K., Ikarashi, T. Clin. Exp. Hypertens. (2005) [Pubmed]
  12. Butylated hydroxyanisole specifically inhibits tumor necrosis factor-induced cytotoxicity and growth enhancement. Brekke, O.L., Shalaby, M.R., Sundan, A., Espevik, T., Bjerve, K.S. Cytokine (1992) [Pubmed]
  13. Effect of intermittent cyclical treatment with etidronate disodium (HEBP) and calcium plus alphacalcidol in postmenopausal osteoporosis. Shiota, E., Tsuchiya, K., Yamaoka, K., Kawano, O. Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association. (2001) [Pubmed]
  14. Discovery of a putative heme-binding protein family (SOUL/HBP) by two-tissue suppression subtractive hybridization and database searches. Zylka, M.J., Reppert, S.M. Brain Res. Mol. Brain Res. (1999) [Pubmed]
  15. Cooperative role for activated alpha4 beta1 integrin and chondroitin sulfate proteoglycans in cell adhesion to the heparin III domain of fibronectin. Identification of a novel heparin and cell binding sequence in repeat III5. Moyano, J.V., Carnemolla, B., Albar, J.P., Leprini, A., Gaggero, B., Zardi, L., Garcia-Pardo, A. J. Biol. Chem. (1999) [Pubmed]
  16. Endocytosis of heparin-binding protein (CAP37) is essential for the enhancement of lipopolysaccharide-induced TNF-alpha production in human monocytes. Heinzelmann, M., Platz, A., Flodgaard, H., Polk, H.C., Miller, F.N. J. Immunol. (1999) [Pubmed]
  17. Antioxidant role of Rhodnius prolixus heme-binding protein. Protection against heme-induced lipid peroxidation. Dansa-Petretski, M., Ribeiro, J.M., Atella, G.C., Masuda, H., Oliveira, P.L. J. Biol. Chem. (1995) [Pubmed]
  18. Insulin sensitivity and cardiovascular risk factors in hypertensive and normotensive native Ghanaians. Amoah, A.G., Schuster, D.P., Gaillard, T., Osei, K. Diabetologia (2003) [Pubmed]
  19. Identification of the receptor scavenging hemopexin-heme complexes. Hvidberg, V., Maniecki, M.B., Jacobsen, C., Højrup, P., Møller, H.J., Moestrup, S.K. Blood (2005) [Pubmed]
  20. Hodgkin's cell lectin: an ectosialyltransferase and lymphocyte agglutinant related to the hepatic asialoglycoprotein receptor. Paietta, E., Hubbard, A.L., Wiernik, P.H., Diehl, V., Stockert, R.J. Cancer Res. (1987) [Pubmed]
  21. Purification of a hexokinase-binding protein from the outer mitochondrial membrane. Felgner, P.L., Messer, J.L., Wilson, J.E. J. Biol. Chem. (1979) [Pubmed]
  22. The First Structure from the SOUL/HBP Family of Heme-binding Proteins, Murine P22HBP. Dias, J.S., Macedo, A.L., Ferreira, G.C., Peterson, F.C., Volkman, B.F., Goodfellow, B.J. J. Biol. Chem. (2006) [Pubmed]
  23. Heparin-binding protein (CAP37) is internalized in monocytes and increases LPS-induced monocyte activation. Heinzelmann, M., Mercer-Jones, M.A., Flodgaard, H., Miller, F.N. J. Immunol. (1998) [Pubmed]
  24. Modulation of lipopolysaccharide-induced monocyte activation by heparin-binding protein and fucoidan. Heinzelmann, M., Polk, H.C., Miller, F.N. Infect. Immun. (1998) [Pubmed]
  25. High density lipoprotein receptors, binding proteins, and ligands. Fidge, N.H. J. Lipid Res. (1999) [Pubmed]
  26. Conformational analysis of hemopexin by Fourier-transform infrared and circular dichroism spectroscopy. Wu, M.L., Morgan, W.T. Proteins (1994) [Pubmed]
  27. Trp-Arg-Trp-Trp-Trp-Trp antagonizes formyl peptide receptor like 2-mediated signaling. Shin, E.H., Lee, H.Y., Kim, S.D., Jo, S.H., Kim, M.K., Park, K.S., Lee, H., Bae, Y.S. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  28. HCV proteins increase expression of heme oxygenase-1 (HO-1) and decrease expression of Bach1 in human hepatoma cells. Ghaziani, T., Shan, Y., Lambrecht, R.W., Donohue, S.E., Pietschmann, T., Bartenschlager, R., Bonkovsky, H.L. J. Hepatol. (2006) [Pubmed]
  29. Evidence for a novel heme-binding protein, HasAh, in Alzheimer disease. Castellani, R.J., Harris, P.L., Lecroisey, A., Izadi-Pruneyre, N., Wandersman, C., Perry, G., Smith, M.A. Antioxid. Redox Signal. (2000) [Pubmed]
  30. Contact-system activation in children with vasculitis. Kahn, R., Herwald, H., Müller-Esterl, W., Schmitt, R., Sjögren, A.C., Truedsson, L., Karpman, D. Lancet (2002) [Pubmed]
  31. Spurious hypertension in the obese patient. Effect of sphygmomanometer cuff size on prevalence of hypertension. Linfors, E.W., Feussner, J.R., Blessing, C.L., Starmer, C.F., Neelon, F.A., McKee, P.A. Arch. Intern. Med. (1984) [Pubmed]
  32. Self-measured versus ambulatory blood pressure in the diagnosis of hypertension. Hond, E.D., Celis, H., Fagard, R., Keary, L., Leeman, M., O'Brien, E., Vandenhoven, G., Staessen, J.A. J. Hypertens. (2003) [Pubmed]
  33. Expression of high density lipoprotein-binding protein messenger ribonucleic acid in the rat ovary and its regulation by gonadotropin. Chen, Z., Menon, K.M. Endocrinology (1994) [Pubmed]
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