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AZGP1  -  alpha-2-glycoprotein 1, zinc-binding

Homo sapiens

Synonyms: ZA2G, ZAG, ZNGP1, Zinc-alpha-2-glycoprotein, Zn-alpha-2-GP, ...
 
 
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Disease relevance of AZGP1

 

High impact information on AZGP1

  • ZAG stimulates lipid degradation in adipocytes and causes the extensive fat losses associated with some advanced cancers [5].
  • The 2.8 angstrom crystal structure of ZAG resembles a class I major histocompatibility complex (MHC) heavy chain, but ZAG does not bind the class I light chain beta2-microglobulin [5].
  • Zn-alpha2-glycoprotein (ZAG) is a soluble protein that is present in serum and other body fluids [5].
  • Positive staining for MUC1, a gene highly expressed in the subgroups with "aggressive" clinicopathological features, was associated with an elevated risk of recurrence (P = 0.003), whereas strong staining for AZGP1, a gene highly expressed in the other subgroup, was associated with a decreased risk of recurrence (P = 0.0008) [6].
  • Because white adipose tissue (WAT) is an endocrine organ secreting a wide range of protein factors, including those involved in lipid metabolism, we have investigated whether ZAG is produced locally by adipocytes [3].
 

Chemical compound and disease context of AZGP1

 

Biological context of AZGP1

 

Anatomical context of AZGP1

  • A decrease in zinc-alpha2-glycoprotein (AZGP1) mRNA levels in malignant prostate epithelium was previously shown to predict biochemical recurrence, as defined by rising levels of serum PSA after radical prostatectomy [2].
  • ZAG mRNA was detected in 3T3-L1 cells, before and after the induction of differentiation, with the level increasing progressively after differentiation with a peak at days 8-10 [3].
  • These data indicate that the function of ZAG has diverged from the peptide presentation and T-cell interaction functions of class I molecules [4].
  • ZAG mRNA was detected by RT-PCR in the mouse WAT depots examined (epididymal, perirenal, s.c., and mammary gland) and in interscapular brown fat [3].
  • Northern-blot analysis showed that the Zn-alpha 2-gp gene is expressed in liver and normal breast, but not in placenta, ovary and thyroid [10].
 

Associations of AZGP1 with chemical compounds

  • Both dexamethasone and a beta3 agonist, BRL 37344, increased ZAG mRNA levels in 3T3-L1 adipocytes [3].
  • Here we show, using serum-derived and bacterial recombinant protein, that ZAG binds the fluorophore-tagged fatty acid 11-(dansylamino)undecanoic acid (DAUDA) and, by competition, natural fatty acids such as arachidonic, linolenic, eicosapentaenoic, and docosahexaenoic acids [9].
  • Addition of fatty acids to ZAG alters its intrinsic (tryptophan) fluorescence emission spectrum, providing a strong indication that ligand binds in the expected position close to a cluster of exposed tryptophan side chains in the groove [9].
  • Finally, considering the lack of polymorphism in the Zn-alpha 2-gp gene in comparison with MHC genes, putative roles for this human glycoprotein in the transport of nonpolymorphic substances or in intercellular recognition processes are proposed [11].
  • The PPARgamma agonist rosiglitazone induced a 3-fold increase in ZAG mRNA level, while TNF-alpha led to a 4-fold decrease [12].
 

Other interactions of AZGP1

 

Analytical, diagnostic and therapeutic context of AZGP1

References

  1. Mapping of the human Zn-alpha 2-glycoprotein gene (AZGP1) to chromosome 7q22 by in situ hybridization. Pendás, A.M., Matilla, T., Uría, J.A., Freije, J.P., Fueyo, A., Estivill, X., López-Otín, C. Cytogenet. Cell Genet. (1994) [Pubmed]
  2. Zinc-alpha2-glycoprotein expression as a predictor of metastatic prostate cancer following radical prostatectomy. Henshall, S.M., Horvath, L.G., Quinn, D.I., Eggleton, S.A., Grygiel, J.J., Stricker, P.D., Biankin, A.V., Kench, J.G., Sutherland, R.L. J. Natl. Cancer Inst. (2006) [Pubmed]
  3. Zinc-alpha2-glycoprotein, a lipid mobilizing factor, is expressed in adipocytes and is up-regulated in mice with cancer cachexia. Bing, C., Bao, Y., Jenkins, J., Sanders, P., Manieri, M., Cinti, S., Tisdale, M.J., Trayhurn, P. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  4. Biochemical characterization and crystalization of human Zn-alpha2-glycoprotein, a soluble class I major histocompatibility complex homolog. Sánchez, L.M., López-Otín, C., Bjorkman, P.J. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  5. Crystal structure of human ZAG, a fat-depleting factor related to MHC molecules. Sánchez, L.M., Chirino, A.J., Bjorkman, P. Science (1999) [Pubmed]
  6. Gene expression profiling identifies clinically relevant subtypes of prostate cancer. Lapointe, J., Li, C., Higgins, J.P., van de Rijn, M., Bair, E., Montgomery, K., Ferrari, M., Egevad, L., Rayford, W., Bergerheim, U., Ekman, P., DeMarzo, A.M., Tibshirani, R., Botstein, D., Brown, P.O., Brooks, J.D., Pollack, J.R. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  7. Glucocorticoids and androgens up-regulate the Zn-alpha 2-glycoprotein messenger RNA in human breast cancer cells. López-Boado, Y.S., Díez-Itza, I., Tolivia, J., López-Otín, C. Breast Cancer Res. Treat. (1994) [Pubmed]
  8. Complete amino acid sequence of human plasma Zn-alpha 2-glycoprotein and its homology to histocompatibility antigens. Araki, T., Gejyo, F., Takagaki, K., Haupt, H., Schwick, H.G., Bürgi, W., Marti, T., Schaller, J., Rickli, E., Brossmer, R. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  9. Hydrophobic ligand binding by Zn-alpha 2-glycoprotein, a soluble fat-depleting factor related to major histocompatibility complex proteins. Kennedy, M.W., Heikema, A.P., Cooper, A., Bjorkman, P.J., Sanchez, L.M. J. Biol. Chem. (2001) [Pubmed]
  10. Human Zn-alpha 2-glycoprotein cDNA cloning and expression analysis in benign and malignant breast tissues. Freije, J.P., Fueyo, A., Uría, J., López-Otín, C. FEBS Lett. (1991) [Pubmed]
  11. Human Zn-alpha 2-glycoprotein: complete genomic sequence, identification of a related pseudogene and relationship to class I major histocompatibility complex genes. Freije, J.P., Fueyo, A., Uría, J.A., Velasco, G., Sánchez, L.M., López-Boado, Y.S., López-Otín, C. Genomics (1993) [Pubmed]
  12. Zinc-alpha2-glycoprotein, a lipid mobilizing factor, is expressed and secreted by human (SGBS) adipocytes. Bao, Y., Bing, C., Hunter, L., Jenkins, J.R., Wabitsch, M., Trayhurn, P. FEBS Lett. (2005) [Pubmed]
  13. Impaired secretory function of the prostate in men with oligo-asthenozoospermia. Ahlgren, G., Rannevik, G., Lilja, H. J. Androl. (1995) [Pubmed]
  14. Expression of Zn-alpha 2-glycoprotein and PSP-94 in prostatic adenocarcinoma. An immunohistochemical study of 88 cases. Gagnon, S., Têtu, B., Dubé, J.Y., Tremblay, R.R. Am. J. Pathol. (1990) [Pubmed]
  15. Toward defining the human parotid gland salivary proteome and peptidome: identification and characterization using 2D SDS-PAGE, ultrafiltration, HPLC, and mass spectrometry. Hardt, M., Thomas, L.R., Dixon, S.E., Newport, G., Agabian, N., Prakobphol, A., Hall, S.C., Witkowska, H.E., Fisher, S.J. Biochemistry (2005) [Pubmed]
  16. A new polymorphic and multicopy MHC gene family related to nonmammalian class I. Leelayuwat, C., Townend, D.C., Degli-Esposti, M.A., Abraham, L.J., Dawkins, R.L. Immunogenetics (1994) [Pubmed]
  17. The conformation and stability of human Zn-alpha 2-glycoprotein in aqueous and methanolic solutions. Karpenko, V., Kaupová, M., Kodícek, M. Biophys. Chem. (1997) [Pubmed]
  18. Molecular cloning and chromosomal assignment of the gene for human Zn-alpha 2-glycoprotein. Ueyama, H., Deng, H.X., Ohkubo, I. Biochemistry (1993) [Pubmed]
 
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