Zinc-alpha-2-glycoprotein is a protein that in humans is encoded by the AZGP1 gene.[5] AZGP1, also referred to as zinc-alpha-2-glycoprotein (ZAG), is a glycoprotein with a molecular weight of 38-40 kDa.[6] In 1961, AZGP1 was initially isolated from normal human plasma and named as ZAG due to its distinctive electrophoretic mobility within the alpha-2 region and its ability to bind to zinc.[6] Subsequent analysis further identified its specific location on a particular chromosome on chromosome 7q22.1 by fluorescence in situ hybridization. AZGP1 is widely expressed in various tissues and body fluids, including the breast, stomach, liver, prostate, plasma, urine, and saliva.[7]

AZGP1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesAZGP1, ZA2G, ZAG, alpha-2-glycoprotein 1, zinc-binding
External IDsOMIM: 194460; MGI: 103163; HomoloGene: 915; GeneCards: AZGP1; OMA:AZGP1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001185

NM_013478

RefSeq (protein)

NP_001176

NP_038506

Location (UCSC)Chr 7: 99.97 – 99.98 MbChr 5: 137.98 – 137.99 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

This gene expresses a soluble protein that stimulates lipolysis, induces a reduction in body fat in mice, is associated with the cachexia related to cancer, and is known to be expressed in secretory cells of lung epithelium.[8] In 2009, it was found that smoking increases expression of this gene, which is why smoking cessation leads to weight gain.[8] Decreased circulating AZGP1 levels are associated with diabetes 2.[9]


AZGP1 has been identified as a biomarker in cancer patients, with its role varying depending on the specific type of cancer. Low expression of AZGP1 is correlated with unfavorable outcomes in gastric cancer, esophageal squamous cell carcinoma, liver cancer, bladder cancer, and prostate cancer. For example, AZGP1 is a potential biomarker for predicting surgical failure and negatively regulates angiogenesis in prostate cancer.[10][11] Elevated levels of AZGP1 have been significantly associated with poor overall survival and disease-free survival in colon cancer.[12]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000160862Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000037053Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: AZGP1 alpha-2-glycoprotein 1, zinc-binding".
  6. ^ a b Burgi W, Schmid K (April 1961). "Preparation and properties of Zn-alpha 2-glycoprotein of normal human plasma". The Journal of Biological Chemistry. 236 (24): 1066–1074. doi:10.1016/S0021-9258(18)64243-7. PMID 13689030.
  7. ^ Hassan MI, Waheed A, Yadav S, Singh TP, Ahmad F (June 2008). "Zinc alpha 2-glycoprotein: a multidisciplinary protein". Molecular Cancer Research. 6 (6): 892–906. doi:10.1158/1541-7786.MCR-07-2195. PMID 18567794.
  8. ^ a b Vanni H, Kazeros A, Wang R, Harvey BG, Ferris B, De BP, et al. (May 2009). "Cigarette smoking induces overexpression of a fat-depleting gene AZGP1 in the human". Chest. 135 (5): 1197–1208. doi:10.1378/chest.08-1024. PMC 2679098. PMID 19188554.
  9. ^ Diniz Pereira J, Gomes Fraga V, Morais Santos AL, Carvalho MD, Caramelli P, Braga Gomes K (March 2021). "Alzheimer's disease and type 2 diabetes mellitus: A systematic review of proteomic studies". Journal of Neurochemistry. 156 (6): 753–756. doi:10.1111/jnc.15166. PMID 32909269.
  10. ^ Wen RM, Qiu Z, Marti GE, Peterson EE, Marques FJ, Bermudez A, et al. (April 2024). "AZGP1 deficiency promotes angiogenesis in prostate cancer". Journal of Translational Medicine. 22 (1): 383. doi:10.1186/s12967-024-05183-x. PMC 11044612. PMID 38659028.
  11. ^ Brooks JD, Wei W, Pollack JR, West RB, Shin JH, Sunwoo JB, et al. (November 2016). "Loss of Expression of AZGP1 Is Associated With Worse Clinical Outcomes in a Multi-Institutional Radical Prostatectomy Cohort". The Prostate. 76 (15): 1409–1419. doi:10.1186/s12967-024-05183-x. PMC 5557496. PMID 27325561.
  12. ^ Fang YY, Huang JM, Wen JY, Li JD, Shen JH, Zeng DT, et al. (2022). "AZGP1 Up-Regulation is a Potential Target for Andrographolide Reversing Radioresistance of Colorectal Cancer". Pharmacogenomics and Personalized Medicine. 15: 999–1017. doi:10.2147/PGPM.S360147. PMC 9758989. PMID 36536885.

Further reading

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  • Tada T, Ohkubo I, Niwa M, Sasaki M, Tateyama H, Eimoto T (September 1991). "Immunohistochemical localization of Zn-alpha 2-glycoprotein in normal human tissues". The Journal of Histochemistry and Cytochemistry. 39 (9): 1221–1226. doi:10.1177/39.9.1918940. PMID 1918940. S2CID 687025.
  • Shibata S, Miura K (1982). "Nephritogenic glycoprotein. IX. Plasma Zn-alpha2-glycoprotein as a second source of nephritogenic glycoprotein in urine". Nephron. 31 (2): 170–176. doi:10.1159/000182638. PMID 6896906.
  • Ueyama H, Deng HX, Ohkubo I (December 1993). "Molecular cloning and chromosomal assignment of the gene for human Zn-alpha 2-glycoprotein". Biochemistry. 32 (48): 12968–12976. doi:10.1021/bi00211a004. PMID 8241150.
  • Freije JP, Fueyo A, Uría JA, Velasco G, Sánchez LM, López-Boado YS, López-Otín C (December 1993). "Human Zn-alpha 2-glycoprotein: complete genomic sequence, identification of a related pseudogene and relationship to class I major histocompatibility complex genes". Genomics. 18 (3): 575–587. doi:10.1016/S0888-7543(05)80359-3. PMID 8307568.
  • Brysk MM, Lei G, Rajaraman S, Selvanayagam P, Rassekh CH, Brysk H, et al. (1997). "Gene expression of zinc-alpha 2-glycoprotein in normal human epidermal and buccal epithelia". In Vivo. 11 (3): 271–274. PMID 9239523.
  • Ogikubo O, Maeda T, Yamane T, Ohtsuka T, Ohkubo I, Takahashi S, et al. (November 1998). "Regulation of Zn-alpha2-glycoprotein-mediated cell adhesion by kininogens and their derivatives". Biochemical and Biophysical Research Communications. 252 (1): 257–262. doi:10.1006/bbrc.1998.9614. PMID 9813179.
  • Lei G, Brysk H, Arany I, Tyring SK, Srinivasan G, Brysk MM (October 1999). "Characterization of zinc-alpha(2)-glycoprotein as a cell adhesion molecule that inhibits the proliferation of an oral tumor cell line". Journal of Cellular Biochemistry. 75 (1): 160–169. doi:10.1002/(SICI)1097-4644(19991001)75:1<160::AID-JCB16>3.0.CO;2-B. PMID 10462714. S2CID 11549967.
  • Davidsson P, Nilsson CL (December 1999). "Peptide mapping of proteins in cerebrospinal fluid utilizing a rapid preparative two-dimensional electrophoretic procedure and matrix-assisted laser desorption/ionization mass spectrometry". Biochimica et Biophysica Acta. 1473 (2–3): 391–399. doi:10.1016/s0304-4165(99)00197-x. PMID 10594376.
  • Diniz Pereira J, Gomes Fraga V, Morais Santos AL, Carvalho MD, Caramelli P, Braga Gomes K (March 2021). "Alzheimer's disease and type 2 diabetes mellitus: A systematic review of proteomic studies". Journal of Neurochemistry. 156 (6): 753–756. doi:10.1111/jnc.15166. PMID 32909269.
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