The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

HPX  -  hemopexin

Homo sapiens

Synonyms: Beta-1B-glycoprotein, Hemopexin
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of HPX

  • Sn-protoporphyrin IX (SnPP), an inhibitor of heme oxygenase and a potential therapeutic agent for neonatal hyperbilirubinemia, is bound tightly by hemopexin [1].
  • We have immunostained a large group of ductal carcinoma in situ and invasive breast carcinomas using a monoclonal antibody (5ST-4A9) raised against the hemopexin-like domain of human ST3 [2].
  • Retinal pigment epithelial cells have been found to bind and internalize heme-hemopexin in a temperature-dependent, saturable, and specific manner, analogous to the receptor-mediated endocytic system of hepatoma cells [3].
  • Thus, intra renal infusion of isolated plasma hemopexin into rats induced minimal change like glomerular lesions and proteinuria [4].
  • BACKGROUND: Previous studies into the relevance of a putative circulating factor in the pathogenesis of minimal change nephrotic syndrome have opened the possibility that plasma hemopexin might be an important effector molecule in this disorder [4].

Psychiatry related information on HPX


High impact information on HPX


Chemical compound and disease context of HPX


Biological context of HPX

  • During cell migration, MT1-MMP binds to CD44H, a major hyaluronan receptor, through the hemopexin-like (HPX) domain and localizes at the migration front [14].
  • This is the first evidence of mobility of the Hpx domain in relation to the catalytic domain, providing an important clue toward the understanding of the collagenase-collagen interaction and subsequent collagenolysis [15].
  • Computer-assisted analysis of the internal homology in amino acid sequence indicates that hemopexin consists of two similar halves, thus suggesting duplication of an ancestral gene [16].
  • TIMP-2 binds to both the hemopexin C domain of progelatinase A and the active site of membrane type-1 (MT1) MMP [17].
  • When dimerization was blocked by coexpressing either a membrane-bound or a soluble form of the Hpx domain, cell surface collagenolytic activity was inhibited in a dose-dependent manner [18].

Anatomical context of HPX

  • We have determined the complete primary structure of human hemopexin, a plasma beta-glycoprotein that specifically binds one heme with high affinity and transports it to hepatocytes for salvage of the iron [16].
  • Immunoinhibition experiments using the antibody against the placental receptor revealed inhibition of binding of 125I-hemopexin to human leukemia K562 and HL 60 cells, thereby strongly supporting that the polypeptide isolated from the human placenta was the hemopexin receptor [19].
  • A hemopexin receptor detected in detergent-solubilized placental membranes was purified from the human placenta, using hemopexin-Sepharose affinity chromatography [19].
  • To explore the possible function of this domain, we purified a recombinant MT6-MMP with the hemopexin-like domain as a soluble form using a Madin-Darby canine kidney cell line as a producer [20].
  • It is thought that by complexing heme, the Hx and Alb can prevent the toxic effects of extracellular heme in blood plasma [21].

Associations of HPX with chemical compounds

  • Structure of human hemopexin: O-glycosyl and N-glycosyl sites and unusual clustering of tryptophan residues [22].
  • Two of the five glucosamine oligosaccharides are present in a histidine-rich sequence of the middle region of the protein, in which the histidines flank beta-turns presumably at the surface of hemopexin [22].
  • The cloned cDNA encodes a protein of 562 amino acids with a domain organization similar to that of other MT-MMPs, including a prodomain with a cysteine switch, a catalytic domain with the zinc-binding site, a hemopexin-like domain, and a COOH-terminal extension rich in hydrophobic residues [23].
  • Dissecting the role of matrix metalloproteinases (MMP) and integrin alpha(v)beta3 in angiogenesis in vitro: absence of hemopexin C domain bioactivity, but membrane-Type 1-MMP and alpha(v)beta3 are critical [24].
  • The hemopexin-SnPP interaction, like that of heme-hemopexin, is dependent on the histidine residues of hemopexin [1].

Physical interactions of HPX


Regulatory relationships of HPX


Other interactions of HPX


Analytical, diagnostic and therapeutic context of HPX


  1. Interaction of hemopexin with Sn-protoporphyrin IX, an inhibitor of heme oxygenase. Role for hemopexin in hepatic uptake of Sn-protoporphyrin IX and induction of mRNA for heme oxygenase. Morgan, W.T., Alam, J., Deaciuc, V., Muster, P., Tatum, F.M., Smith, A. J. Biol. Chem. (1988) [Pubmed]
  2. Stromelysin 3: an independent prognostic factor for relapse-free survival in node-positive breast cancer and demonstration of novel breast carcinoma cell expression. Ahmad, A., Hanby, A., Dublin, E., Poulsom, R., Smith, P., Barnes, D., Rubens, R., Anglard, P., Hart, I. Am. J. Pathol. (1998) [Pubmed]
  3. Hemopexin in the human retina: protection of the retina against heme-mediated toxicity. Hunt, R.C., Hunt, D.M., Gaur, N., Smith, A. J. Cell. Physiol. (1996) [Pubmed]
  4. Protease activity of plasma hemopexin. Bakker, W.W., Borghuis, T., Harmsen, M.C., van den Berg, A., Kema, I.P., Niezen, K.E., Kapojos, J.J. Kidney Int. (2005) [Pubmed]
  5. The influence of heme-binding proteins in heme-catalyzed oxidations. Vincent, S.H., Grady, R.W., Shaklai, N., Snider, J.M., Muller-Eberhard, U. Arch. Biochem. Biophys. (1988) [Pubmed]
  6. Different faces of the heme-heme oxygenase system in inflammation. Wagener, F.A., Volk, H.D., Willis, D., Abraham, N.G., Soares, M.P., Adema, G.J., Figdor, C.G. Pharmacol. Rev. (2003) [Pubmed]
  7. CD44 directs membrane-type 1 matrix metalloproteinase to lamellipodia by associating with its hemopexin-like domain. Mori, H., Tomari, T., Koshikawa, N., Kajita, M., Itoh, Y., Sato, H., Tojo, H., Yana, I., Seiki, M. EMBO J. (2002) [Pubmed]
  8. Roles of heme iron-coordinating histidine residues of human hemopexin expressed in baculovirus-infected insect cells. Satoh, T., Satoh, H., Iwahara, S., Hrkal, Z., Peyton, D.H., Muller-Eberhard, U. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  9. The rat and human hemopexin genes contain an identical interleukin-6 response element that is not a target of CAAT enhancer-binding protein isoforms. Immenschuh, S., Nagae, Y., Satoh, H., Baumann, H., Muller-Eberhard, U. J. Biol. Chem. (1994) [Pubmed]
  10. Acute phase proteins in male Chinese schizophrenic patients in Singapore. Wong, C.T., Tsoi, W.F., Saha, N. Schizophr. Res. (1996) [Pubmed]
  11. Synthesis of hemopexin and cysteine protease inhibitor is coordinately regulated by HSF-II and interferon-beta 2 in rat hepatoma cells. Baumann, H., Muller-Eberhard, U. Biochem. Biophys. Res. Commun. (1987) [Pubmed]
  12. Hemolytic anemias. Diagnosis and management. Tabbara, I.A. Med. Clin. North Am. (1992) [Pubmed]
  13. Duchenne muscular dystrophy carrier detection using logistic discrimination: serum creatine kinase and hemopexin in combination. Percy, M.E., Andrews, D.F., Thompson, M.W. Am. J. Med. Genet. (1981) [Pubmed]
  14. CD44 binding through the hemopexin-like domain is critical for its shedding by membrane-type 1 matrix metalloproteinase. Suenaga, N., Mori, H., Itoh, Y., Seiki, M. Oncogene (2005) [Pubmed]
  15. X-ray structure of human proMMP-1: new insights into procollagenase activation and collagen binding. Jozic, D., Bourenkov, G., Lim, N.H., Visse, R., Nagase, H., Bode, W., Maskos, K. J. Biol. Chem. (2005) [Pubmed]
  16. 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]
  17. Tissue inhibitor of metalloproteinases-4 inhibits but does not support the activation of gelatinase A via efficient inhibition of membrane type 1-matrix metalloproteinase. Bigg, H.F., Morrison, C.J., Butler, G.S., Bogoyevitch, M.A., Wang, Z., Soloway, P.D., Overall, C.M. Cancer Res. (2001) [Pubmed]
  18. Cell Surface Collagenolysis Requires Homodimerization of the Membrane-bound Collagenase MT1-MMP. Itoh, Y., Ito, N., Nagase, H., Evans, R.D., Bird, S.A., Seiki, M. Mol. Biol. Cell (2006) [Pubmed]
  19. Isolation of the hemopexin receptor from human placenta. Taketani, S., Kohno, H., Naitoh, Y., Tokunaga, R. J. Biol. Chem. (1987) [Pubmed]
  20. Clusterin, an abundant serum factor, is a possible negative regulator of MT6-MMP/MMP-25 produced by neutrophils. Matsuda, A., Itoh, Y., Koshikawa, N., Akizawa, T., Yana, I., Seiki, M. J. Biol. Chem. (2003) [Pubmed]
  21. The effects of heme-binding proteins on the peroxidative and catalatic activities of hemin. Grinberg, L.N., O'Brien, P.J., Hrkal, Z. Free Radic. Biol. Med. (1999) [Pubmed]
  22. Structure of human hemopexin: O-glycosyl and N-glycosyl sites and unusual clustering of tryptophan residues. Takahashi, N., Takahashi, Y., Putnam, F.W. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  23. Human MT6-matrix metalloproteinase: identification, progelatinase A activation, and expression in brain tumors. Velasco, G., Cal, S., Merlos-Suárez, A., Ferrando, A.A., Alvarez, S., Nakano, A., Arribas, J., López-Otín, C. Cancer Res. (2000) [Pubmed]
  24. Dissecting the role of matrix metalloproteinases (MMP) and integrin alpha(v)beta3 in angiogenesis in vitro: absence of hemopexin C domain bioactivity, but membrane-Type 1-MMP and alpha(v)beta3 are critical. Nisato, R.E., Hosseini, G., Sirrenberg, C., Butler, G.S., Crabbe, T., Docherty, A.J., Wiesner, M., Murphy, G., Overall, C.M., Goodman, S.L., Pepper, M.S. Cancer Res. (2005) [Pubmed]
  25. Identification of the tissue inhibitor of metalloproteinases-2 (TIMP-2) binding site on the hemopexin carboxyl domain of human gelatinase A by site-directed mutagenesis. The hierarchical role in binding TIMP-2 of the unique cationic clusters of hemopexin modules III and IV. Overall, C.M., King, A.E., Sam, D.K., Ong, A.D., Lau, T.T., Wallon, U.M., DeClerck, Y.A., Atherstone, J. J. Biol. Chem. (1999) [Pubmed]
  26. Human 92 kDa type IV collagenase: functional analysis of fibronectin and carboxyl-end domains. Strongin, A.Y., Collier, I.E., Krasnov, P.A., Genrich, L.T., Marmer, B.L., Goldberg, G.I. Kidney Int. (1993) [Pubmed]
  27. Oligomerization through hemopexin and cytoplasmic domains regulates the activity and turnover of membrane-type 1 matrix metalloproteinase. Lehti, K., Lohi, J., Juntunen, M.M., Pei, D., Keski-Oja, J. J. Biol. Chem. (2002) [Pubmed]
  28. Production of hemopexin by TNF-alpha stimulated human mesangial cells. Kapojos, J.J., van den Berg, A., van Goor, H., te Loo, M.W., Poelstra, K., Borghuis, T., Bakker, W.W. Kidney Int. (2003) [Pubmed]
  29. Expression of human pro-matrix metalloproteinase 3 that lacks the N-terminal 34 residues in Escherichia coli: autoactivation and interaction with tissue inhibitor of metalloproteinase 1 (TIMP-1). Suzuki, K., Kan, C.C., Hung, W., Gehring, M.R., Brew, K., Nagase, H. Biol. Chem. (1998) [Pubmed]
  30. Front-cell-specific expression of membrane-type 1 matrix metalloproteinase and gelatinase A during cohort migration of colon carcinoma cells induced by hepatocyte growth factor/scatter factor. Nabeshima, K., Inoue, T., Shimao, Y., Okada, Y., Itoh, Y., Seiki, M., Koono, M. Cancer Res. (2000) [Pubmed]
  31. Matrix metalloproteinase activity inactivates the CXC chemokine stromal cell-derived factor-1. McQuibban, G.A., Butler, G.S., Gong, J.H., Bendall, L., Power, C., Clark-Lewis, I., Overall, C.M. J. Biol. Chem. (2001) [Pubmed]
  32. The hemopexin-like C-terminal domain of membrane type 1 matrix metalloproteinase regulates proteolysis of a multifunctional protein, gC1qR. Rozanov, D.V., Ghebrehiwet, B., Postnova, T.I., Eichinger, A., Deryugina, E.I., Strongin, A.Y. J. Biol. Chem. (2002) [Pubmed]
  33. Identification and structural and functional characterization of human enamelysin (MMP-20). Llano, E., Pendás, A.M., Knäuper, V., Sorsa, T., Salo, T., Salido, E., Murphy, G., Simmer, J.P., Bartlett, J.D., López-Otín, C. Biochemistry (1997) [Pubmed]
  34. Importance of ligand-induced conformational changes in hemopexin for receptor-mediated heme transport. Smith, A., Tatum, F.M., Muster, P., Burch, M.K., Morgan, W.T. J. Biol. Chem. (1988) [Pubmed]
  35. The primary structure of human hemopexin deduced from cDNA sequence: evidence for internal, repeating homology. Altruda, F., Poli, V., Restagno, G., Argos, P., Cortese, R., Silengo, L. Nucleic Acids Res. (1985) [Pubmed]
WikiGenes - Universities