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Gene Review

PRG2  -  proteoglycan 2, bone marrow (natural...

Homo sapiens

Synonyms: BMPG, Bone marrow proteoglycan, MBP, MBP1, Proteoglycan 2
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Disease relevance of PRG2

  • Eosinophil granule MBP is initially translated as a nontoxic precursor (proMBP), containing a 9.9 kilodalton acidic pro-portion that is believed to neutralize MBP toxicity [1].
  • In addition, this form of SCF induced the expression of a pertussis toxin-sensitive G(i) protein, G(i3) that interacts with MBP to trigger mast cell non-IgE-dependent activation in a manner similar to other cationic compounds such as compound 48/80 [2].
  • EMBP is directly implicated in epithelial cell damage, exfoliation, and bronchospasm in allergic diseases such as asthma [3].
  • Eosinophil-derived agents such as PAF, LTC4, MBP and ECP might be responsible for submucosal oedema and non-specific bronchial hyperreactivity which are characteristic features of late-phase reactions [4].
  • In bronchial asthma, considerable evidence exists that the eosinophil releases granule proteins, especially the major basic protein (MBP), which in turn mediate tissue abnormalities [5].

Psychiatry related information on PRG2

  • The presence in CSF of MS patients of a cross-reactive Id to different MBP peptides is indicative of an immune response to this encephalitogenic myelin protein in a segment of MS patients [6].
  • The mean counts per minute (cpm) value of serum anti-MBP antibody of the catatonia group was significantly higher than that of the patients with other forms of schizophrenic psychoses (p less than .05) [7].
  • An increase in MBP degradation was detected in patients with neurological complications, such as AIDS dementia complex (ADC) or progressive multifocal leukoencephalopathy (PML), when compared with patients with no neurological symptoms (NA) or with other neurological opportunistic infections (OI) [8].
  • Results show that increased CSF levels of MBP were detected in all patients with severe ADC (10/10) and, less often, in subjects with mild (2/7) or moderate dementia (7/16) [9].
  • Based on a suspected pathological relationship of autoimmunity in Alzheimer's disease (AD), antibodies to myelin basic protein (MBP) were investigated in the sera of AD patients, healthy controls and disease controls [10].

High impact information on PRG2


Chemical compound and disease context of PRG2


Biological context of PRG2


Anatomical context of PRG2


Associations of PRG2 with chemical compounds

  • The pro-MBP subunit contains 12 cysteine residues, of which 10 have been accounted for [26].
  • Eosinophil granule major basic protein (MBP), a potent toxin for helminths and various cell types, is a 13.8-kD single polypeptide rich in arginine with a calculated isoelectric point (pI) of 10 [23].
  • The NH2-terminal half has a predicted pI of 3.7 and is hydrophilic, while the COOH-terminal half (corresponding to mature MBP) has a predicted pI of 11.1 and is hydrophobic [27].
  • In fact, cord blood-derived mast cells cocultured with 3T3 in the presence of antisense for SCF or cocultured with fibroblasts that do not express the membrane form of SCF were inhibited in their histamine-releasing activity toward MBP [2].
  • Our analysis suggests that EMBP specifically binds heparin [3].

Physical interactions of PRG2

  • However, stimulation with MBP did not produce an increase in the binding activity of nuclear factor (NF)-kappaB or activator protein-1 [28].

Regulatory relationships of PRG2


Other interactions of PRG2

  • In addition, it is shown that commercial polyclonal anti-PAPP-A is polyspecific, also reacting with MBP [32].
  • We have defined a novel synergistic, as opposed to antagonistic, combinatorial interaction between GATA-1 and PU.1, and a unique repressor role for certain C/EBPepsilon isoforms in the transcriptional regulation of a model eosinophil granulocyte gene, the major basic protein (MBP) [33].
  • IL-5-like products from these putative activated lymphocytes might perpetuate (a) eosinophil production by the bone marrow, (b) its release into the circulation, (c) its migration into bronchial tissue and (d) activation to release PAF, LTC4, MBP, etc.(ABSTRACT TRUNCATED AT 400 WORDS)[4]
  • The fibroblast-derived membrane form of stem cell factor (SCF) was found to be involved in the mast cell increased responsiveness to MBP [2].
  • To determine the functionality of this site, we tested whether GATA-1 and GATA-2, either individually or in combination, can transactivate the MBP promoter in the Jurkat T cell line [34].

Analytical, diagnostic and therapeutic context of PRG2


  1. Localization of pregnancy-associated plasma protein-A and colocalization of pregnancy-associated plasma protein-A messenger ribonucleic acid and eosinophil granule major basic protein messenger ribonucleic acid in placenta. Bonno, M., Oxvig, C., Kephart, G.M., Wagner, J.M., Kristensen, T., Sottrup-Jensen, L., Gleich, G.J. Lab. Invest. (1994) [Pubmed]
  2. Non-IgE-dependent activation of human lung- and cord blood-derived mast cells is induced by eosinophil major basic protein and modulated by the membrane form of stem cell factor. Piliponsky, A.M., Gleich, G.J., Nagler, A., Bar, I., Levi-Schaffer, F. Blood (2003) [Pubmed]
  3. Crystal structure of the eosinophil major basic protein at 1.8 A. An atypical lectin with a paradigm shift in specificity. Swaminathan, G.J., Weaver, A.J., Loegering, D.A., Checkel, J.L., Leonidas, D.D., Gleich, G.J., Acharya, K.R. J. Biol. Chem. (2001) [Pubmed]
  4. Leucocytes in asthma. Kay, A.B. Immunol. Invest. (1988) [Pubmed]
  5. The biology of the eosinophilic leukocyte. Gleich, G.J., Adolphson, C.R., Leiferman, K.M. Annu. Rev. Med. (1993) [Pubmed]
  6. A cross-reactive anti-myelin basic protein idiotope in cerebrospinal fluid cells in multiple sclerosis. Zhou, S.R., Maier, C.C., Mitchell, G.W., LaGanke, C.C., Blalock, J.E., Whitaker, J.N. Neurology (1998) [Pubmed]
  7. Myelin basic protein antibodies in catatonic schizophrenia. Rimón, R., Ahokas, A., Ruutiainen, J., Halonen, P. The Journal of clinical psychiatry. (1986) [Pubmed]
  8. Myelin degrading activity in the CSF of HIV-1-infected patients with neurological diseases. Liuzzi, G.M., Mastroianni, C.M., Fanelli, M., Massetti, A.P., Vullo, V., Delia, S., Riccio, P. Neuroreport (1994) [Pubmed]
  9. Cerebrospinal fluid myelin basic protein as predictive marker of demyelination in AIDS dementia complex. Liuzzi, G.M., Mastroianni, C.M., Vullo, V., Jirillo, E., Delia, S., Riccio, P. J. Neuroimmunol. (1992) [Pubmed]
  10. Immunoblot detection of antibodies to myelin basic protein in Alzheimer's disease patients. Singh, V.K., Yang, Y.Y., Singh, E.A. Neurosci. Lett. (1992) [Pubmed]
  11. Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Wucherpfennig, K.W., Strominger, J.L. Cell (1995) [Pubmed]
  12. Transgenic mice that express a myelin basic protein-specific T cell receptor develop spontaneous autoimmunity. Goverman, J., Woods, A., Larson, L., Weiner, L.P., Hood, L., Zaller, D.M. Cell (1993) [Pubmed]
  13. MHC-restricted depletion of human myelin basic protein-reactive T cells by T cell vaccination. Zhang, J., Medaer, R., Stinissen, P., Hafler, D., Raus, J. Science (1993) [Pubmed]
  14. Microbial epitopes act as altered peptide ligands to prevent experimental autoimmune encephalomyelitis. Ruiz, P.J., Garren, H., Hirschberg, D.L., Langer-Gould, A.M., Levite, M., Karpuj, M.V., Southwood, S., Sette, A., Conlon, P., Steinman, L. J. Exp. Med. (1999) [Pubmed]
  15. In vivo survival of viral antigen-specific T cells that induce experimental autoimmune encephalomyelitis. Ufret-Vincenty, R.L., Quigley, L., Tresser, N., Pak, S.H., Gado, A., Hausmann, S., Wucherpfennig, K.W., Brocke, S. J. Exp. Med. (1998) [Pubmed]
  16. A correlative triad of gadolinium-DTPA MRI, EDSS, and CSF-MBP in relapsing multiple sclerosis patients treated with high-dose intravenous methylprednisolone. Barkhof, F., Frequin, S.T., Hommes, O.R., Lamers, K., Scheltens, P., van Geel, W.J., Valk, J. Neurology (1992) [Pubmed]
  17. Analysis of signaling events associated with activation of neutrophil superoxide anion production by eosinophil granule major basic protein. Haskell, M.D., Moy, J.N., Gleich, G.J., Thomas, L.L. Blood (1995) [Pubmed]
  18. Estramustine-binding protein and specific binding of the anti-mitotic compound estramustine in astrocytoma. Bergenheim, A.T., Björk, P., Bergh, J., von Schoultz, E., Svedberg, H., Henriksson, R. Cancer Res. (1994) [Pubmed]
  19. Cytophilic and cytotoxic properties of human eosinophil peroxidase plus major basic protein. Samoszuk, M.K., Petersen, A., Gidanian, F., Rietveld, C. Am. J. Pathol. (1988) [Pubmed]
  20. Antibacterial properties of eosinophil major basic protein and eosinophil cationic protein. Lehrer, R.I., Szklarek, D., Barton, A., Ganz, T., Hamann, K.J., Gleich, G.J. J. Immunol. (1989) [Pubmed]
  21. Comparative structure, proximal promoter elements, and chromosome location of the human eosinophil major basic protein genes. Plager, D.A., Weiler, D.A., Loegering, D.A., Johnson, W.B., Haley, L., Eddy, R.L., Shows, T.B., Gleich, G.J. Genomics (2001) [Pubmed]
  22. Localization and cellular distribution of pregnancy-associated plasma protein-a and major basic protein in human ovary and corpora lutea throughout the menstrual cycle. Rhoton-Vlasak, A., Gleich, G.J., Bischof, P., Chegini, N. Fertil. Steril. (2003) [Pubmed]
  23. Acidic precursor revealed in human eosinophil granule major basic protein cDNA. Barker, R.L., Gleich, G.J., Pease, L.R. J. Exp. Med. (1988) [Pubmed]
  24. Eosinophil major basic protein stimulates neutrophil superoxide production by a class IA phosphoinositide 3-kinase and protein kinase C-zeta-dependent pathway. Shenoy, N.G., Gleich, G.J., Thomas, L.L. J. Immunol. (2003) [Pubmed]
  25. Proteinase inhibition by proform of eosinophil major basic protein (pro-MBP) is a multistep process of intra- and intermolecular disulfide rearrangements. Glerup, S., Boldt, H.B., Overgaard, M.T., Sottrup-Jensen, L., Giudice, L.C., Oxvig, C. J. Biol. Chem. (2005) [Pubmed]
  26. Complex of pregnancy-associated plasma protein-A and the proform of eosinophil major basic protein. Disulfide structure and carbohydrate attachment. Overgaard, M.T., Sorensen, E.S., Stachowiak, D., Boldt, H.B., Kristensen, L., Sottrup-Jensen, L., Oxvig, C. J. Biol. Chem. (2003) [Pubmed]
  27. Isolation of a complementary DNA clone encoding a precursor to human eosinophil major basic protein. McGrogan, M., Simonsen, C., Scott, R., Griffith, J., Ellis, N., Kennedy, J., Campanelli, D., Nathan, C., Gabay, J. J. Exp. Med. (1988) [Pubmed]
  28. Stimulation of neutrophil interleukin-8 production by eosinophil granule major basic protein. Page, S.M., Gleich, G.J., Roebuck, K.A., Thomas, L.L. Am. J. Respir. Cell Mol. Biol. (1999) [Pubmed]
  29. Stem cell factor influences mast cell mediator release in response to eosinophil-derived granule major basic protein. Furuta, G.T., Ackerman, S.J., Lu, L., Williams, R.E., Wershil, B.K. Blood (1998) [Pubmed]
  30. Augmented expression of tumour necrosis factor-alpha and lymphotoxin in mononuclear cells in multiple sclerosis and optic neuritis. Navikas, V., He, B., Link, J., Haglund, M., Söderström, M., Fredrikson, S., Ljungdahl A, n.u.l.l., Höjeberg, J., Qiao, J., Olsson, T., Link, H. Brain (1996) [Pubmed]
  31. Granulocyte/macrophage-colony stimulating factor in allergen-induced rhinitis: cellular localization, relation to tissue eosinophilia and influence of topical corticosteroid. Nouri-Aria, K.T., Masuyama, K., Jacobson, M.R., Rak, S., Lowhagen, O., Schotman, E., Hamid, Q., Durham, S. Int. Arch. Allergy Immunol. (1998) [Pubmed]
  32. Circulating human pregnancy-associated plasma protein-A is disulfide-bridged to the proform of eosinophil major basic protein. Oxvig, C., Sand, O., Kristensen, T., Gleich, G.J., Sottrup-Jensen, L. J. Biol. Chem. (1993) [Pubmed]
  33. Novel combinatorial interactions of GATA-1, PU.1, and C/EBPepsilon isoforms regulate transcription of the gene encoding eosinophil granule major basic protein. Du, J., Stankiewicz, M.J., Liu, Y., Xi, Q., Schmitz, J.E., Lekstrom-Himes, J.A., Ackerman, S.J. J. Biol. Chem. (2002) [Pubmed]
  34. Mechanisms of transcription in eosinophils: GATA-1, but not GATA-2, transactivates the promoter of the eosinophil granule major basic protein gene. Yamaguchi, Y., Ackerman, S.J., Minegishi, N., Takiguchi, M., Yamamoto, M., Suda, T. Blood (1998) [Pubmed]
  35. Biochemical and amino acid sequence analysis of human eosinophil granule major basic protein. Wasmoen, T.L., Bell, M.P., Loegering, D.A., Gleich, G.J., Prendergast, F.G., McKean, D.J. J. Biol. Chem. (1988) [Pubmed]
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