Zinc 2-Glycoprotein: A Multidisciplinary Protein

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, India.
Molecular Cancer Research (Impact Factor: 4.38). 07/2008; 6(6):892-906. DOI: 10.1158/1541-7786.MCR-07-2195
Source: PubMed

ABSTRACT Zinc alpha 2-glycoprotein (ZAG) is a protein of interest because of its ability to play many important functions in the human body, including fertilization and lipid mobilization. After the discovery of this molecule, during the last 5 decades, various studies have been documented on its structure and functions, but still, it is considered as a protein with an unknown function. Its expression is regulated by glucocorticoids. Due to its high sequence homology with lipid-mobilizing factor and high expression in cancer cachexia, it is considered as a novel adipokine. On the other hand, structural organization and fold is similar to MHC class I antigen-presenting molecule; hence, ZAG may have a role in the expression of the immune response. The function of ZAG under physiologic and cancerous conditions remains mysterious but is considered as a tumor biomarker for various carcinomas. There are several unrelated functions that are attributed to ZAG, such as RNase activity, regulation of melanin production, hindering tumor proliferation, and transport of nephritic by-products. This article deals with the discussion of the major aspects of ZAG from its gene structure to function and metabolism.

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Available from: Md Imtaiyaz Hassan, Sep 12, 2015
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    • "On the other hand, although none of the koala AZGP1 sequences showed any diversity in our analysis, there are three separate but closely related transcripts, which may indicate a more complex function than originally expected. AZGP1 seems to have a wide variety of functions, from tumor suppression to regulating the creation of melanin to RNase properties (reviewed in Hassan et al. 2008). This may explain the "
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    ABSTRACT: The study of the koala transcriptome has the potential to advance our understanding of its immunome-immunological reaction of a given host to foreign antigens-and to help combat infectious diseases (e.g., chlamydiosis) that impede ongoing conservation efforts. We used Illumina sequencing of cDNA to characterize genes expressed in two different koala tissues of immunological importance, blood and spleen. We generated nearly 600 million raw sequence reads, and about 285 million of these were subsequently assembled and condensed into ~70,000 subcomponents that represent putative transcripts. We annotated ~16 % of these subcomponents and identified those related to infection and the immune response, including Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), major histocompatibility complex (MHC) genes, and koala retrovirus (KoRV). Using phylogenetic analyses, we identified 29 koala genes in these target categories and report their concordance with currently accepted gene groups. By mapping multiple sequencing reads to transcripts, we identified 56 putative SNPs in genes of interest. The distribution of these SNPs indicates that MHC genes (34 SNPs) are more diverse than KoRV (12 SNPs), TLRs (8 SNPs), or RLRs (2 SNPs). Our sequence data also indicate that KoRV sequences are highly expressed in the transcriptome. Our efforts have produced full-length sequences for potentially important immune genes in koala, which should serve as targets for future investigations that aim to conserve koala populations.
    Immunogenetics 03/2015; 67(5-6). DOI:10.1007/s00251-015-0833-6 · 2.23 Impact Factor
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    • "Zinc-α-2-glycoprotein (ZAG) is a 40-kilodalton (kDa) single-chain polypeptide with many important functions, such as fertilization and lipid mobilization [1] . ZAG is structurally similar to major histocompatibility complex class I molecules and considered to be an adipokine [2] [3] [4] . "
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    ABSTRACT: Objective: To investigate the levels of zinc-α-2-glycoprotein (ZAG) among Omani AIDS patients receiving combined antiretroviral therapy (cART). Methods: A total of 80 Omani AIDS patients (45 males and 35 females), average age of 36 years, who were receiving cART at the Sultan Qaboos University Hospital (SQUH), Muscat, Oman, were tested for the levels of ZAG. In addition, 80 healthy blood donors (46 males and 34 females), average age of 26 years, attending the SQUH Blood Bank, were tested in parallel as a control group. Measurement of the ZAG levels was performed using a competitive enzyme-linked immunosorbent assay and in accordance with the manufacturer's instructions. Results: The ZAG levels were found to be significantly higher among AIDS patients compared to the healthy individuals (P=0.033). A total of 56 (70%) of the AIDS patients were found to have higher levels of ZAG and 16 (20%) AIDS patients were found to have high ZAG levels, which are significantly (P>0.031) associated with weight loss. Conclusions: ZAG levels are high among Omani AIDS patients on cART and this necessitates the measurement of ZAG on routine basis, as it is associated with weight loss.
    Asian Pacific Journal of Tropical Biomedicine 08/2014; 4(8):610-3. DOI:10.12980/APJTB.4.201414B126
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    • "This result suggests that the increase in circulating ZAG that occurs during HD process is related to factors that are lacking in PD. Glucocorticoids are described to increase ZAG secretion [35], [36]. And cortisol level has been shown to be increased by hemodialysis session [37] suggesting that glucocorticoids could enhance ZAG secretion and contribute to the perdialytic increase in plasma ZAG concentration. "
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    ABSTRACT: Zinc-α2-glycoprotein (ZAG), a potent cachectic factor, is increased in patients undergoing maintenance dialysis. However, there is no data for patients before initiation of renal replacement therapy. The purpose of the present study was to assess the relationship between plasma ZAG concentration and renal function in patients with a large range of glomerular filtration rate (GFR). Plasma ZAG concentration and its relationship to GFR were investigated in 71 patients with a chronic kidney disease (CKD) stage 1 to 5, 17 chronic hemodialysis (HD), 8 peritoneal dialysis (PD) and 18 non-CKD patients. Plasma ZAG concentration was 2.3-fold higher in CKD stage 5 patients and 3-fold higher in HD and PD patients compared to non-CKD controls (P<0.01). The hemodialysis session further increased plasma ZAG concentration (+39%, P<0.01). An inverse relationship was found between ZAG levels and plasma protein (rs = -0.284; P<0.01), albumin (rs = -0.282, P<0.05), hemoglobin (rs = -0.267, P<0.05) and HDL-cholesterol (rs = -0.264, P<0.05) and a positive correlation were seen with plasma urea (rs = 0.283; P<0.01). In multiple regression analyses, plasma urea and HDL-cholesterol were the only variables associated with plasma ZAG (r2 = 0.406, P<0.001). In CKD-5 patients, plasma accumulation of ZAG was not correlated with protein energy wasting. Further prospective studies are however needed to better elucidate the potential role of ZAG in end-stage renal disease.
    PLoS ONE 07/2014; 9(7):e103475. DOI:10.1371/journal.pone.0103475 · 3.23 Impact Factor
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