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Gene Review

CHP1  -  calcineurin-like EF-hand protein 1

Homo sapiens

Synonyms: CHP, Calcineurin B homologous protein 1, Calcineurin B-like protein, Calcium-binding protein CHP, Calcium-binding protein p22, ...
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Disease relevance of CHP


Psychiatry related information on CHP


High impact information on CHP

  • These findings suggest that CHP serves as an obligatory subunit that is required both for supporting the basic activity and regulating the pH-sensing of NHE1 via interactions between distinct parts of these proteins [6].
  • The plasma membrane Na+/H+ exchangers (NHE) require calcineurin B homologous protein (CHP) as an obligatory binding partner for ion transport [6].
  • Structure-based mutagenesis revealed the importance of hydrophobic interactions between CHP/NHE1 for the function of NHE1 [6].
  • The phosphorylation state of CHP may therefore be an important signal controlling mitogenic regulation of NHE1 [7].
  • To explore this possibility, we studied the effects of desferoxamine, a compound which chelates iron, on viability of CHP 126 and CHP 100, two human neuroblastoma cell lines [8].

Chemical compound and disease context of CHP


Biological context of CHP

  • Ubiquitous calcineurin B homologous protein (CHP or p22) is co-localized and co-immunoprecipitated with expressed NHE1, NHE2, or NHE3 independently of its myristoylation and Ca2+ binding, and its binding site was identified as the juxtamembrane region within the carboxyl-terminal cytoplasmic domain of exchangers [14].
  • We have cloned a new rat CHP isoform (rCHP2) and characterized the binding property to NHEs and the tissue distribution. rCHP2 binds to the juxtamembrane region of plasma membrane-type NHE isoforms (NHE1-5) in vivo and in vitro as well as rCHP1 (original rat CHP) [15].
  • This substrate specificity correlates with the oligosaccharide residues thus far defined on glycoproteins of CHP 134 cells since NeuAc and Fuc alpha 1----3GlcNAc have yet to be detected on the same oligosaccharide antenna [9].
  • The relationship between the quantity of silver-stained interphasic nucleolar organizer regions (NORs) and nuclear synthetic activity, caryotype, and growth rate was studied in two established neuroblastoma cell lines (CHP 212 and HTB 10) [16].
  • In contrast to cortisol, which inhibits both 19-s and 7-s antibody formation, CHP does not diminish the number of cells producing either antibody [3].

Anatomical context of CHP

  • Calcineurin homologous protein (CHP) is a Ca2+-binding protein that directly interacts with and regulates the activity of all plasma-membrane Na+/H+-exchanger (NHE) family members [17].
  • Moreover, prolonged activation of Jurkat cells was associated with a decreased abundance of CHP, suggesting a possible regulatory mechanism allowing activation of calcineurin [18].
  • In Jurkat and HeLa cells, overexpression of CHP specifically impaired the nuclear translocation and transcriptional activity of NFAT but had no effect on AP-1 transcriptional activity and only a small (<25%) inhibitory effect on the transcriptional activity of NFkappaB [18].
  • KIF1Bbeta2, capable of interacting with CHP, is localized to synaptic vesicles [19].
  • These results suggest that CHP2 functions in the absorptive epithelium for the intestine with NHE(s) [15].

Associations of CHP with chemical compounds

  • Lesser interindividual variations were observed with respect to human liver GST activities towards benzo(a)pyrene-4,5-oxide (BaPO, 9-fold variation), 1-chloro-2,4-dinitrobenzene (CDNB, 8.5-fold variation), cumene hydroperoxide (CHP, 5-fold variation), and p-nitrophenyl acetate (NPA, 4-fold variation) [20].
  • In this study, we used biocompatible nanogels composed of a polysaccharide pullulan backbone with hydrophobic cholesterol moieties (cholesterol-bearing pullulan, CHP) as artificial chaperones to inhibit the formation of Abeta-(1-42) fibrils with marked amyloidgenic activity and cytotoxicity [21].
  • In particular, the irreversible aggregation of carbonic anhydrase B (CAB) upon heating was completely prevented by complexation between the heat-denatured enzyme and hydrogel nanoparticles formed by the self-aggregation of cholesteryl group-bearing pullulan (CHP) [22].
  • However, line CHP 100 proved hypersensitive to amsacrine, bleomycin, methotrexate and vincristine yet refractory to cisplatin, carboplatin and VP-16, compared with the other two lines [23].
  • The first step was also activated the surface of CHP to induce primary amine terminator [24].

Physical interactions of CHP


Regulatory relationships of CHP

  • In conclusion, SK-N-MC cells which grow rapidly and have a high plating efficiency, express IGF-I, while CHP cells that grow more slowly express IGF-II [25].

Other interactions of CHP

  • In this study, we characterized the function of another isoform of CHP (designated CHP2) that has a 61% amino acid identity with CHP1 [26].
  • IGFBP-2 secretion correlated positively with IGF-II secretion in CHP cells (r=0.85, P=0.05) and negatively with IGF-I (r= -0.9, P<0.01) in SK-N-MC cells [25].
  • The results of this study show that the level of CHP, a peptide that mimics dopamine in many of its pharmacologic actions, is lower in brains of alcohol-preferring C57BL mice compared to alcohol non-preferring DBA2 mice [5].
  • Neither CoQ10 nor vitamin E correlated with paraoxonase (PON) activity or cholesteryl-ester hydroperoxides (CHP) [27].
  • CONCLUSIONS: These findings indicate that CHP/ESO is a promising polyvalent cancer vaccine targeting NY-ESO-1 [28].

Analytical, diagnostic and therapeutic context of CHP


  1. A serine/threonine kinase which causes apoptosis-like cell death interacts with a calcineurin B-like protein capable of binding Na(+)/H(+) exchanger. Matsumoto, M., Miyake, Y., Nagita, M., Inoue, H., Shitakubo, D., Takemoto, K., Ohtsuka, C., Murakami, H., Nakamura, N., Kanazawa, H. J. Biochem. (2001) [Pubmed]
  2. Enhancement of in vitro activity against neuroblastoma by doxorubicin and deferoxamine. Blatt, J., Huntley, D. J. Natl. Cancer Inst. (1989) [Pubmed]
  3. A selective inhibitor of the elicitation of immune-mediated reactions. Ferraresi, R.W., Rooks, W.H., Nakano, G.M., Ringold, H.J., Kidson, C. J. Allergy Clin. Immunol. (1975) [Pubmed]
  4. Dermatomyositis, lobar panniculitis and inflammatory myopathy with abundant macrophages. Carrera, E., Lobrinus, J.A., Spertini, O., Gherardi, R.K., Kuntzer, T. Neuromuscul. Disord. (2006) [Pubmed]
  5. Role of endogenous cyclo(His-Pro) in voluntary alcohol consumption by alcohol-preferring C57BL mice. Prasad, C. Peptides (2001) [Pubmed]
  6. Crystal structure of CHP2 complexed with NHE1-cytosolic region and an implication for pH regulation. Ammar, Y.B., Takeda, S., Hisamitsu, T., Mori, H., Wakabayashi, S. EMBO J. (2006) [Pubmed]
  7. A calcineurin homologous protein inhibits GTPase-stimulated Na-H exchange. Lin, X., Barber, D.L. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  8. Antineuroblastoma activity of desferoxamine in human cell lines. Blatt, J., Stitely, S. Cancer Res. (1987) [Pubmed]
  9. Purification and characterization of GDP-L-Fuc-N-acetyl-beta-D-glucosaminide alpha 1----3fucosyltransferase from human neuroblastoma cells. Unusual substrate specificities of the tumor enzyme. Foster, C.S., Gillies, D.R., Glick, M.C. J. Biol. Chem. (1991) [Pubmed]
  10. Plasma neuropeptide Y of children with neuroblastoma in relation to stage, age and prognosis, and tissue neuropeptide Y. Dötsch, J., Christiansen, H., Hänze, J., Lampert, F., Rascher, W. Regul. Pept. (1998) [Pubmed]
  11. Expression of human glutamate receptors (GluR) in neuroblastoma cell lines. Korczak, B., McWhinnie, E.A., Fletcher, E.J., Kamboj, R.K. Neuroreport (1995) [Pubmed]
  12. Mechanism of antineuroblastoma activity of deferoxamine in vitro. Blatt, J., Taylor, S.R., Stitely, S. J. Lab. Clin. Med. (1988) [Pubmed]
  13. A fast protein liquid chromatography (FPLC) method for study of thyrotropin-releasing hormone (TRH) and its metabolite histidyl-proline diketopiperazine (CHP) in human blood: degradation in liver and pancreatic diseases. Duntas, L., Nelson, D.K., Grab, B.M., Rosenthal, J., Maier, V. Neuropeptides (1993) [Pubmed]
  14. Calcineurin homologous protein as an essential cofactor for Na+/H+ exchangers. Pang, T., Su, X., Wakabayashi, S., Shigekawa, M. J. Biol. Chem. (2001) [Pubmed]
  15. Calcineurin homologous protein isoform 2 (CHP2), Na+/H+ exchangers-binding protein, is expressed in intestinal epithelium. Inoue, H., Nakamura, Y., Nagita, M., Takai, T., Masuda, M., Nakamura, N., Kanazawa, H. Biol. Pharm. Bull. (2003) [Pubmed]
  16. Relationship between interphasic nucleolar organizer regions and growth rate in two neuroblastoma cell lines. Derenzini, M., Pession, A., Farabegoli, F., Trerè, D., Badiali, M., Dehan, P. Am. J. Pathol. (1989) [Pubmed]
  17. Crystallization and preliminary crystallographic analysis of the human calcineurin homologous protein CHP2 bound to the cytoplasmic region of the Na+/H+ exchanger NHE1. Ben Ammar, Y., Takeda, S., Sugawara, M., Miyano, M., Mori, H., Wakabayashi, S. Acta Crystallograph. Sect. F Struct. Biol. Cryst. Commun. (2005) [Pubmed]
  18. Inhibition of calcineurin phosphatase activity by a calcineurin B homologous protein. Lin, X., Sikkink, R.A., Rusnak, F., Barber, D.L. J. Biol. Chem. (1999) [Pubmed]
  19. KIF1Bbeta2, capable of interacting with CHP, is localized to synaptic vesicles. Nakamura, N., Miyake, Y., Matsushita, M., Tanaka, S., Inoue, H., Kanazawa, H. J. Biochem. (2002) [Pubmed]
  20. Human variability in hepatic glutathione S-transferase-mediated conjugation of aflatoxin B1-epoxide and other substrates. Slone, D.H., Gallagher, E.P., Ramsdell, H.S., Rettie, A.E., Stapleton, P.L., Berlad, L.G., Eaton, D.L. Pharmacogenetics (1995) [Pubmed]
  21. Inhibition of the formation of amyloid beta-protein fibrils using biocompatible nanogels as artificial chaperones. Ikeda, K., Okada, T., Sawada, S., Akiyoshi, K., Matsuzaki, K. FEBS Lett. (2006) [Pubmed]
  22. Molecular chaperone-like activity of hydrogel nanoparticles of hydrophobized pullulan: thermal stabilization with refolding of carbonic anhydrase B. Akiyoshi, K., Sasaki, Y., Sunamoto, J. Bioconjug. Chem. (1999) [Pubmed]
  23. Use of human neuroblastoma continuous cell lines for in vitro drug sensitivity screening. Hill, B.T., Whelan, R.D., Hosking, L.K. Investigational new drugs. (1988) [Pubmed]
  24. Immobilization of Chinese herbal medicine onto the surface-modified calcium hydrogenphosphate. Lin, F.H., Dong, G.C., Chen, K.S., Jiang, G.J., Huang, C.W., Sun, J.S. Biomaterials (2003) [Pubmed]
  25. Human neuroblastoma cells use either insulin-like growth factor-I or insulin-like growth factor-II in an autocrine pathway via the IGF-I receptor: variability of IGF, IGF binding protein (IGFBP) and IGF receptor gene expression and IGF and IGFBP secretion in human neuroblastoma cells in relation to cellular proliferation. Kiess, W., Koepf, G., Christiansen, H., Blum, W.F. Regul. Pept. (1997) [Pubmed]
  26. Expression of calcineurin B homologous protein 2 protects serum deprivation-induced cell death by serum-independent activation of Na+/H+ exchanger. Pang, T., Wakabayashi, S., Shigekawa, M. J. Biol. Chem. (2002) [Pubmed]
  27. Coenzyme Q10, antioxidant status and ApoE isoforms. Battino, M., Giunta, S., Galeazzi, L., Galeazzi, R., Mosca, F., Santolini, C., Principi, F., Ferretti, G., Bacchetti, T., Bencivenga, R., Piani, M., Riganello, G., Littarru, G.P. Biofactors (2003) [Pubmed]
  28. In vitro stimulation of CD8 and CD4 T cells by dendritic cells loaded with a complex of cholesterol-bearing hydrophobized pullulan and NY-ESO-1 protein: Identification of a new HLA-DR15-binding CD4 T-cell epitope. Hasegawa, K., Noguchi, Y., Koizumi, F., Uenaka, A., Tanaka, M., Shimono, M., Nakamura, H., Shiku, H., Gnjatic, S., Murphy, R., Hiramatsu, Y., Old, L.J., Nakayama, E. Clin. Cancer Res. (2006) [Pubmed]
  29. A monoclonal antibody detecting an antigen shared by neural and granulocytic cells. Kemshead, J.T., Bicknell, D., Greaves, M.F. Pediatr. Res. (1981) [Pubmed]
  30. Human Thy-1: expression on the cell surface of neuronal and glial cells. Kemshead, J.T., Ritter, M.A., Cotmore, S.F., Greaves, M.F. Brain Res. (1982) [Pubmed]
  31. Identification and characterization of cyclo(His-Pro)-like immunoreactivity in amniotic fluid. Hilton, C.W., Wolf, G.C., Wilber, J.F., Prasad, C., Rogers, D. Peptides (1989) [Pubmed]
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