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Gene Review

HP  -  haptoglobin

Homo sapiens

Synonyms: BP, HP2ALPHA2, HPA1S, Haptoglobin, Zonulin
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Disease relevance of HP

  • Ectopic expression and activation of wild-type STAT3 or STAT3SA in HepG2 hepatoma cells similarly enhance transcription through the IL-6-response element of the HP promoter [1].
  • Furthermore, an association between HP type and infarction size was observed, HP 2-2 being associated with smaller infarctions [2].
  • Close linkage of HP on chromosome 16 and MEN-2A is excluded [3].
  • In an earlier paper, positive but nonsignificant lod scores were found in pair-wise linkage tests between multiple endocrine neoplasia type 2A (MEN-2A) and both the haptoglobin (HP) locus on chromosome 16 and group-specific component (GC) locus on chromosome 4 [3].
  • This specific receptor-ligand interaction leading to removal from plasma of the Hp-Hb complex-but not free Hp or Hb-now explains the depletion of circulating Hp in individuals with increased intravascular hemolysis [4].

Psychiatry related information on HP

  • The disorders in Hp and Tf circulating levels are highly sensitive to (83%) and specific for (100%) melancholia as opposed to the healthy state [5].
  • We studied the pattern of acute-phase proteins (orosomucoid, C-reactive protein, and haptoglobin) in hepatocellular deficiency due to chronic alcohol consumption, characterized by a decrease in serum transferrin concentration [6].
  • Serum and cerebrospinal fluid (CSF) from 22 ambulatory and 10 institutionalised patients with Alzheimer's disease (AD) and 22 age-matched controls were assayed nephelometrically for concentrations of IgG, IgA, IgM, haptoglobin, transferrin, prealbumin and albumin [7].
  • The present study shows that the pattern of appearance of serum haptoglobin during the neonatal period is associated with ACP1 phenotype suggesting some important function of this polymorphic enzyme in human development [8].
  • On the other hand, the Hp 2-2 value is not increased in the systematic schizophrenias, but it displays a relative overplus in the unsystematic forms [9].

High impact information on HP


Chemical compound and disease context of HP


Biological context of HP

  • The allele frequency of HP A*2SS, which is common in the European population, is less frequent than HP A*2V1 in the Japanese population [18].
  • Of these three markers, only the HP locus was found to be codeleted with the TAT locus on the del(16) chromosome [19].
  • The DNA sequence(s) responsible for the normally high level of HP expression in liver either reside outside the 3.3-kb regulatory region of the HP chimeric gene or this region contains a suppressor sequence affecting tissue specific expression in the liver [20].
  • A significant decrease in HP 2-1 frequency was found, suggesting protection for heterozygotes in both DM and DR (with a relative risk of about 0.31) [21].
  • APRT was found to be distal to HP and FRA16D and was localized at 16q24, making the gene order cen-FRA16B-HP-FRA16D-APRT-qter [22].

Anatomical context of HP


Associations of HP with chemical compounds


Physical interactions of HP

  • Based on these results, we propose that Hpr mediates the high affinity binding of TLF-1 to T. b. brucei through a haptoglobin-like receptor [28].
  • Its function has remained unknown until recently when CD163 was identified as the endocytic receptor binding hemoglobin (Hb) in complex with the plasma protein haptoglobin (Hp) [4].
  • We have previously shown that Hp interacts with the beta2-integrin CD11b/CD18 [29].
  • Haptoglobin polymorphisms result in proteins with altered haemoglobin-binding capacity and different antioxidant, iron-recycling, and immune functions [30].
  • The ApoA-I structure was analyzed to detect the site bound by Hpt [31].

Regulatory relationships of HP


Other interactions of HP


Analytical, diagnostic and therapeutic context of HP


  1. The carboxyl-terminal region of STAT3 controls gene induction by the mouse haptoglobin promoter. Kim, H., Baumann, H. J. Biol. Chem. (1997) [Pubmed]
  2. Haptoglobin groups in acute myocardial infarction. Fröhlander, N., Johnson, O. Hum. Hered. (1989) [Pubmed]
  3. Progress toward resolving the possible linkage of multiple endocrine neoplasia type 2A to haptoglobin and group-specific loci: use of restriction fragment length polymorphisms extends exclusion region. Kidd, K.K., Kidd, J.R., Castiglione, C.M., Pakstis, A.J., Sparkes, R.S. Genet. Epidemiol. (1986) [Pubmed]
  4. CD163: a signal receptor scavenging haptoglobin-hemoglobin complexes from plasma. Graversen, J.H., Madsen, M., Moestrup, S.K. Int. J. Biochem. Cell Biol. (2002) [Pubmed]
  5. Disturbances in acute phase plasma proteins during melancholia: additional evidence for the presence of an inflammatory process during that illness. Maes, M., Scharpe, S., Bosmans, E., Vandewoude, M., Suy, E., Uyttenbroeck, W., Cooreman, W., Vandervorst, C., Raus, J. Prog. Neuropsychopharmacol. Biol. Psychiatry (1992) [Pubmed]
  6. Evolutionary changes in acute-phase proteins in alcoholic hepatocellular diseases. Perier, C., Chamson, A., Engler, R., Frey, J. Clin. Chem. (1983) [Pubmed]
  7. CSF in Alzheimer's disease. Studies on blood-brain barrier function and intrathecal protein synthesis. Elovaara, I., Icén, A., Palo, J., Erkinjuntti, T. J. Neurol. Sci. (1985) [Pubmed]
  8. Serum haptoglobin appearance during neonatal period is associated with acid phosphatase (ACP1) phenotype. Bottini, E., Carapella, E., Scacchi, R., Lucarini, N., Gloria-Bottini, F., Pascone, R., Bonci, E., Maggioni, G. Early Hum. Dev. (1985) [Pubmed]
  9. Genetic markers for schizophrenic subgroups. Lange, V. Psychiatria clinica. (1982) [Pubmed]
  10. Haptoglobin phenotype and vascular complications in patients with diabetes. Levy, A.P., Roguin, A., Hochberg, I., Herer, P., Marsh, S., Nakhoul, F.M., Skorecki, K. N. Engl. J. Med. (2000) [Pubmed]
  11. Collagenase expression in the lungs of transgenic mice causes pulmonary emphysema. D'Armiento, J., Dalal, S.S., Okada, Y., Berg, R.A., Chada, K. Cell (1992) [Pubmed]
  12. Effect of the haptoglobin phenotype on the size of a myocardial infarct. Chapelle, J.P., Albert, A., Smeets, J.P., Heusghem, C., Kulbertus, H.E. N. Engl. J. Med. (1982) [Pubmed]
  13. Identification of the haemoglobin scavenger receptor. Kristiansen, M., Graversen, J.H., Jacobsen, C., Sonne, O., Hoffman, H.J., Law, S.K., Moestrup, S.K. Nature (2001) [Pubmed]
  14. Serum haptoglobin: a novel marker of adiposity in humans. Chiellini, C., Santini, F., Marsili, A., Berti, P., Bertacca, A., Pelosini, C., Scartabelli, G., Pardini, E., López-Soriano, J., Centoni, R., Ciccarone, A.M., Benzi, L., Vitti, P., Del Prato, S., Pinchera, A., Maffei, M. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  15. Haptoglobin polymorphism in breast cancer patients form Jordan. Awadallah, S.M., Atoum, M.F. Clin. Chim. Acta (2004) [Pubmed]
  16. Effect of sucrose on inflammatory markers in overweight humans. Sørensen, L.B., Raben, A., Stender, S., Astrup, A. Am. J. Clin. Nutr. (2005) [Pubmed]
  17. Serum sialic acid and sialoglycoproteins in asymptomatic carotid artery atherosclerosis. ARIC Investigators. Atherosclerosis Risk in Communities. Lindberg, G., Råstam, L., Nilsson-Ehle, P., Lundblad, A., Ranstam, J., Folsom, A.R., Burke, G.L. Atherosclerosis (1999) [Pubmed]
  18. Haptoglobin subtyping with anti-haptoglobin alpha chain antibodies. Shindo, S. Electrophoresis (1990) [Pubmed]
  19. Inherited and de novo deletion of the tyrosine aminotransferase gene locus at 16q22.1----q22.3 in a patient with tyrosinemia type II. Natt, E., Westphal, E.M., Toth-Fejel, S.E., Magenis, R.E., Buist, N.R., Rettenmeier, R., Scherer, G. Hum. Genet. (1987) [Pubmed]
  20. A human (3.3 kb) haptoglobin-CAT transgene is modulated in lungs of transgenic mice by inflammation. Martinez, A., Jansen, L., Buchanan, J.M., Adrian, G.S., Yang, F., Herbert, D.C., Weaker, F.J., Walter, C.A., Bowman, B.H. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  21. Haptoglobin phenotypes in diabetes mellitus and diabetic retinopathy. Chandra, T., Lakshmi, C.N., Padma, T., Vidyavathi, M., Satapathy, M. Hum. Hered. (1991) [Pubmed]
  22. A new location for the human adenine phosphoribosyltransferase gene (APRT) distal to the haptoglobin (HP) and fra(16)(q23)(FRA16D) loci. Fratini, A., Simmers, R.N., Callen, D.F., Hyland, V.J., Tischfield, J.A., Stambrook, P.J., Sutherland, G.R. Cytogenet. Cell Genet. (1986) [Pubmed]
  23. Haptoglobin phenotyping from older bloodstains by enzyme immunoassay and haptoglobin phenotypes within a Nebraska Caucasian population. Roy, R., Roy, I.C. J. Forensic Sci. (1991) [Pubmed]
  24. Polymorphisms in the human haptoglobin gene cluster: chromosomes with multiple haptoglobin-related (Hpr) genes. Maeda, N., McEvoy, S.M., Harris, H.F., Huisman, T.H., Smithies, O. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  25. Prohaptoglobin is proteolytically cleaved in the endoplasmic reticulum by the complement C1r-like protein. Wicher, K.B., Fries, E. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  26. Identification of haptoglobin as an alternative ligand for CD11b/CD18. El Ghmati, S.M., Van Hoeyveld, E.M., Van Strijp, J.G., Ceuppens, J.L., Stevens, E.A. J. Immunol. (1996) [Pubmed]
  27. Polymorphism of esterase D and haptoglobin in the Madras City population. Raj, B.K., Damodaran, C., Sekharan, P.C. Gene geography : a computerized bulletin on human gene frequencies. (1991) [Pubmed]
  28. Haptoglobin-related protein mediates trypanosome lytic factor binding to trypanosomes. Drain, J., Bishop, J.R., Hajduk, S.L. J. Biol. Chem. (2001) [Pubmed]
  29. Haptoglobin interacts with the human mast cell line HMC-1 and inhibits its spontaneous proliferation. El-Ghmati, S.M., Arredouani, M., Van Hoeyveld, E.M., Ceuppens, J.L., Stevens, E.A. Scand. J. Immunol. (2002) [Pubmed]
  30. Seasonal childhood anaemia in West Africa is associated with the haptoglobin 2-2 genotype. Atkinson, S.H., Rockett, K., Sirugo, G., Bejon, P.A., Fulford, A., O'Connell, M.A., Bailey, R., Kwiatkowski, D.P., Prentice, A.M. PLoS Med. (2006) [Pubmed]
  31. Assignment of the binding site for haptoglobin on apolipoprotein A-I. Spagnuolo, M.S., Cigliano, L., D'Andrea, L.D., Pedone, C., Abrescia, P. J. Biol. Chem. (2005) [Pubmed]
  32. Haptoglobin inhibits lecithin-cholesterol acyltransferase in human ovarian follicular fluid. Balestrieri, M., Cigliano, L., Simone, M.L., Dale, B., Abrescia, P. Mol. Reprod. Dev. (2001) [Pubmed]
  33. Haptoglobin type neither influences iron accumulation in normal subjects nor predicts clinical presentation in HFE C282Y haemochromatosis: phenotype and genotype analysis. Carter, K., Bowen, D.J., McCune, C.A., Worwood, M. Br. J. Haematol. (2003) [Pubmed]
  34. Smad proteins suppress CCAAT/enhancer-binding protein (C/EBP) beta- and STAT3-mediated transcriptional activation of the haptoglobin promoter. Zauberman, A., Lapter, S., Zipori, D. J. Biol. Chem. (2001) [Pubmed]
  35. A Unique Loop Extension in the Serine Protease Domain of Haptoglobin Is Essential for CD163 Recognition of the Haptoglobin-Hemoglobin Complex. Nielsen, M.J., Petersen, S.V., Jacobsen, C., Thirup, S., Enghild, J.J., Graversen, J.H., Moestrup, S.K. J. Biol. Chem. (2007) [Pubmed]
  36. Structure and expression of the human haptoglobin locus. Bensi, G., Raugei, G., Klefenz, H., Cortese, R. EMBO J. (1985) [Pubmed]
  37. Genetic markers in renal adenocarcinoma. Germenis, A., Dimopoulos, M.A., Fertakis, A., Dimopoulos, C. J. Urol. (1984) [Pubmed]
  38. Genetic studies of the Macushi and Wapishana Indians. I. Rare genetic variants and a "private polymorphism' of esterase A. Neel, J.V., Tanis, R.J., Migliazza, E.C., Spielman, R.S., Salzano, F., Oliver, W.J., Morrow, M., Bachofer, S. Hum. Genet. (1977) [Pubmed]
  39. The haptoglobin-gene deletion responsible for anhaptoglobinemia. Koda, Y., Soejima, M., Yoshioka, N., Kimura, H. Am. J. Hum. Genet. (1998) [Pubmed]
  40. Simple PCR detection of haptoglobin gene deletion in anhaptoglobinemic patients with antihaptoglobin antibody that causes anaphylactic transfusion reactions. Koda, Y., Watanabe, Y., Soejima, M., Shimada, E., Nishimura, M., Morishita, K., Moriya, S., Mitsunaga, S., Tadokoro, K., Kimura, H. Blood (2000) [Pubmed]
  41. Acute phase reactants and severity of homozygous sickle cell disease. Hedo, C.C., Aken'ova, Y.A., Okpala, I.E., Durojaiye, A.O., Salimonu, L.S. J. Intern. Med. (1993) [Pubmed]
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