AZGP1 explained
Zinc-alpha-2-glycoprotein is a protein that in humans is encoded by the AZGP1 gene.[1] AZGP1, also referred to as zinc-alpha-2-glycoprotein (ZAG), is a glycoprotein with a molecular weight of 38-40 kDa.[2] 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. 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.[3]
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.[4] In 2009, it was found that smoking increases expression of this gene, which is why smoking cessation leads to weight gain. Decreased circulating AZGP1 levels are associated with diabetes 2.[5]
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.[6] [7] Elevated levels of AZGP1 have been significantly associated with poor overall survival and disease-free survival in colon cancer.[8]
Further reading
- Freije JP, Fueyo A, Uría J, López-Otín C . Human Zn-alpha 2-glycoprotein cDNA cloning and expression analysis in benign and malignant breast tissues . FEBS Letters . 290 . 1-2 . 247–249 . September 1991 . 1915885 . 10.1016/0014-5793(91)81271-9 . 2058665 . 1991FEBSL.290..247F .
- Tada T, Ohkubo I, Niwa M, Sasaki M, Tateyama H, Eimoto T . Immunohistochemical localization of Zn-alpha 2-glycoprotein in normal human tissues . The Journal of Histochemistry and Cytochemistry . 39 . 9 . 1221–1226 . September 1991 . 1918940 . 10.1177/39.9.1918940 . 687025 .
- Araki T, Gejyo F, Takagaki K, Haupt H, Schwick HG, Bürgi W, Marti T, Schaller J, Rickli E, Brossmer R . 6 . Complete amino acid sequence of human plasma Zn-alpha 2-glycoprotein and its homology to histocompatibility antigens . Proceedings of the National Academy of Sciences of the United States of America . 85 . 3 . 679–683 . February 1988 . 3422450 . 279618 . 10.1073/pnas.85.3.679 . free .
- Shibata S, Miura K . Nephritogenic glycoprotein. IX. Plasma Zn-alpha2-glycoprotein as a second source of nephritogenic glycoprotein in urine . Nephron . 31 . 2 . 170–176 . 1982 . 6896906 . 10.1159/000182638 .
- Ueyama H, Deng HX, Ohkubo I . Molecular cloning and chromosomal assignment of the gene for human Zn-alpha 2-glycoprotein . Biochemistry . 32 . 48 . 12968–12976 . December 1993 . 8241150 . 10.1021/bi00211a004 .
- Freije JP, Fueyo A, Uría JA, Velasco G, Sánchez LM, López-Boado YS, López-Otín C . 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 . December 1993 . 8307568 . 10.1016/S0888-7543(05)80359-3 .
- Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Research . 6 . 9 . 791–806 . September 1996 . 8889548 . 10.1101/gr.6.9.791 . free .
- Sánchez LM, López-Otín C, Bjorkman PJ . Biochemical characterization and crystalization of human Zn-alpha2-glycoprotein, a soluble class I major histocompatibility complex homolog . Proceedings of the National Academy of Sciences of the United States of America . 94 . 9 . 4626–4630 . April 1997 . 9114041 . 20774 . 10.1073/pnas.94.9.4626 . free .
- Brysk MM, Lei G, Rajaraman S, Selvanayagam P, Rassekh CH, Brysk H, Tyring SK, Arany I . 6 . Gene expression of zinc-alpha 2-glycoprotein in normal human epidermal and buccal epithelia . In Vivo . 11 . 3 . 271–274 . 1997 . 9239523 .
- Lei G, Arany I, Selvanayagam P, Rajaraman S, Ram S, Brysk H, Tyring SK, Brysk MM . 6 . Detection and cloning of epidermal zinc-alpha 2-glycoprotein cDNA and expression in normal human skin and in tumors . Journal of Cellular Biochemistry . 67 . 2 . 216–222 . November 1997 . 9328826 . 10.1002/(SICI)1097-4644(19971101)67:2<216::AID-JCB6>3.0.CO;2-# . 196585165 .
- Ogikubo O, Maeda T, Yamane T, Ohtsuka T, Ohkubo I, Takahashi S, Ohnishi S, Matsui N . 6 . Regulation of Zn-alpha2-glycoprotein-mediated cell adhesion by kininogens and their derivatives . Biochemical and Biophysical Research Communications . 252 . 1 . 257–262 . November 1998 . 9813179 . 10.1006/bbrc.1998.9614 .
- Sánchez LM, Chirino AJ, Bjorkman PJ . Crystal structure of human ZAG, a fat-depleting factor related to MHC molecules . Science . 283 . 5409 . 1914–1919 . March 1999 . 10206894 . 10.1126/science.283.5409.1914 . 1999Sci...283.1914S .
- Lei G, Brysk H, Arany I, Tyring SK, Srinivasan G, Brysk MM . 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 . October 1999 . 10462714 . 10.1002/(SICI)1097-4644(19991001)75:1<160::AID-JCB16>3.0.CO;2-B . 11549967 .
- Davidsson P, Nilsson CL . 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 . December 1999 . 10594376 . 10.1016/s0304-4165(99)00197-x .
- Kennedy MW, Heikema AP, Cooper A, Bjorkman PJ, Sanchez LM . Hydrophobic ligand binding by Zn-alpha 2-glycoprotein, a soluble fat-depleting factor related to major histocompatibility complex proteins . The Journal of Biological Chemistry . 276 . 37 . 35008–35013 . September 2001 . 11425849 . 10.1074/jbc.C100301200 . free .
- Scherer SW, Cheung J, MacDonald JR, Osborne LR, Nakabayashi K, Herbrick JA, Carson AR, Parker-Katiraee L, Skaug J, Khaja R, Zhang J, Hudek AK, Li M, Haddad M, Duggan GE, Fernandez BA, Kanematsu E, Gentles S, Christopoulos CC, Choufani S, Kwasnicka D, Zheng XH, Lai Z, Nusskern D, Zhang Q, Gu Z, Lu F, Zeesman S, Nowaczyk MJ, Teshima I, Chitayat D, Shuman C, Weksberg R, Zackai EH, Grebe TA, Cox SR, Kirkpatrick SJ, Rahman N, Friedman JM, Heng HH, Pelicci PG, Lo-Coco F, Belloni E, Shaffer LG, Pober B, Morton CC, Gusella JF, Bruns GA, Korf BR, Quade BJ, Ligon AH, Ferguson H, Higgins AW, Leach NT, Herrick SR, Lemyre E, Farra CG, Kim HG, Summers AM, Gripp KW, Roberts W, Szatmari P, Winsor EJ, Grzeschik KH, Teebi A, Minassian BA, Kere J, Armengol L, Pujana MA, Estivill X, Wilson MD, Koop BF, Tosi S, Moore GE, Boright AP, Zlotorynski E, Kerem B, Kroisel PM, Petek E, Oscier DG, Mould SJ, Döhner H, Döhner K, Rommens JM, Vincent JB, Venter JC, Li PW, Mural RJ, Adams MD, Tsui LC . 6 . Human chromosome 7: DNA sequence and biology . Science . 300 . 5620 . 767–772 . May 2003 . 12690205 . 2882961 . 10.1126/science.1083423 . 2003Sci...300..767S .
- Diniz Pereira J, Gomes Fraga V, Morais Santos AL, Carvalho MD, Caramelli P, Braga Gomes K . Alzheimer’s disease and type 2 diabetes mellitus: A systematic review of proteomic studies . Journal of Neurochemistry . 156 . 6 . 753-756 . March 2021 . 32909269 . 10.1111/jnc.15166.
- Wen RM, Qiu Z, Marti GE, Peterson EE, Marques FJ, Bermudez A, Wei Y, Nolley R, Lam N, Polasko AL, Chiu CL, Zhang D, Cho S, Karageorgos GM, McDonough E, Chadwick C, Ginty F, Jung KJ, Machiraju R, Mallick P, Crowley L, Pollack JR, Zhao H, Pitteri SJ, Brooks JD . 6 . AZGP1 deficiency promotes angiogenesis in prostate cancer . Journal of Translational Medicine . 22 . 1 . 383 . April 2024 . 38659028 . 11044612 . 10.1186/s12967-024-05183-x . free .
- Brooks JD, Wei W, Pollack JR, West RB, Shin JH, Sunwoo JB, Hawley SJ, Auman H, Newcomb LF, Simko J, Hurtado-Coll A, Troyer DA, Carroll PR, Gleave ME, Lin DW, Nelson PS, Thompson IM, True LD, McKenney JK, Feng Z, Fazli L . 6 . Loss of Expression of AZGP1 Is Associated With Worse Clinical Outcomes in a Multi-Institutional Radical Prostatectomy Cohort . The Prostate . 76 . 15 . 1409–1419 . November 2016 . 27325561 . 5557496 . 10.1002/pros.23225 . free .
- Fang YY, Huang JM, Wen JY, Li JD, Shen JH, Zeng DT, Pan YF, Huang HQ, Huang ZG, Liu LM, Chen G . 6 . AZGP1 Up-Regulation is a Potential Target for Andrographolide Reversing Radioresistance of Colorectal Cancer . Pharmacogenomics and Personalized Medicine . 15 . 999–1017 . 2022 . 36536885 . 9758989 . 10.2147/PGPM.S360147 . free .
Notes and References
- Web site: Entrez Gene: AZGP1 alpha-2-glycoprotein 1, zinc-binding .
- Burgi W, Schmid K . Preparation and properties of Zn-alpha 2-glycoprotein of normal human plasma . The Journal of Biological Chemistry . 236 . 24 . 1066–1074 . April 1961 . 13689030 . 10.1016/S0021-9258(18)64243-7 . free .
- Hassan MI, Waheed A, Yadav S, Singh TP, Ahmad F . Zinc alpha 2-glycoprotein: a multidisciplinary protein . Molecular Cancer Research . 6 . 6 . 892–906 . June 2008 . 18567794 . 10.1158/1541-7786.MCR-07-2195 .
- Vanni H, Kazeros A, Wang R, Harvey BG, Ferris B, De BP, Carolan BJ, Hübner RH, O'Connor TP, Crystal RG . 6 . Cigarette smoking induces overexpression of a fat-depleting gene AZGP1 in the human . Chest . 135 . 5 . 1197–1208 . May 2009 . 19188554 . 2679098 . 10.1378/chest.08-1024 .
- Diniz Pereira J, Gomes Fraga V, Morais Santos AL, Carvalho MD, Caramelli P, Braga Gomes K . Alzheimer’s disease and type 2 diabetes mellitus: A systematic review of proteomic studies . Journal of Neurochemistry . 156 . 6 . 753-756 . March 2021 . 32909269 . 10.1111/jnc.15166.
- Wen RM, Qiu Z, Marti GE, Peterson EE, Marques FJ, Bermudez A, Wei Y, Nolley R, Lam N, Polasko AL, Chiu CL, Zhang D, Cho S, Karageorgos GM, McDonough E, Chadwick C, Ginty F, Jung KJ, Machiraju R, Mallick P, Crowley L, Pollack JR, Zhao H, Pitteri SJ, Brooks JD . 6 . AZGP1 deficiency promotes angiogenesis in prostate cancer . Journal of Translational Medicine . 22 . 1 . 383 . April 2024 . 38659028 . 11044612 . 10.1186/s12967-024-05183-x . free .
- Brooks JD, Wei W, Pollack JR, West RB, Shin JH, Sunwoo JB, Hawley SJ, Auman H, Newcomb LF, Simko J, Hurtado-Coll A, Troyer DA, Carroll PR, Gleave ME, Lin DW, Nelson PS, Thompson IM, True LD, McKenney JK, Feng Z, Fazli L . 6 . Loss of Expression of AZGP1 Is Associated With Worse Clinical Outcomes in a Multi-Institutional Radical Prostatectomy Cohort . The Prostate . 76 . 15 . 1409–1419 . November 2016 . 27325561 . 5557496 . 10.1186/s12967-024-05183-x . free .
- Fang YY, Huang JM, Wen JY, Li JD, Shen JH, Zeng DT, Pan YF, Huang HQ, Huang ZG, Liu LM, Chen G . 6 . AZGP1 Up-Regulation is a Potential Target for Andrographolide Reversing Radioresistance of Colorectal Cancer . Pharmacogenomics and Personalized Medicine . 15 . 999–1017 . 2022 . 36536885 . 9758989 . 10.2147/PGPM.S360147 . free .