Alternative titles; symbols
HGNC Approved Gene Symbol: AZGP1
Cytogenetic location: 7q22.1 Genomic coordinates (GRCh38): 7:99,966,730-99,976,031 (from NCBI)
Burgi and Schmid (1961) first purified zinc-alpha-2-glycoprotein from pooled human plasma and studied its physicochemical properties. The glycoprotein was so named for its electrophoretic mobility in the alpha-2 region and for its ability to bind zinc ions. The ZAG glycoprotein has a molecular mass of 41 kD consisting of 18.2% carbohydrate and a single polypeptide chain.
The complete amino acid sequence and the carbohydrate structure of ZAG were determined by Araki et al. (1988), who calculated the molecular mass to be 38,478 Da.
Ueyama et al. (1991) isolated a cDNA clone for human zinc-alpha-2-glycoprotein. Southern blot analysis suggested the presence of a single gene encoding the protein.
Using a panel of rodent-human somatic cell hybrids, Ueyama et al. (1991) assigned the ZAG gene to human chromosome 7.
By fluorescence in situ hybridization, Ueyama et al. (1993) mapped the functional gene, which they symbolized ZA2G, to 7q22.1. They concluded that at least one of the pseudogenes is closely linked to the functional chain.
Pendas et al. (1994) also used fluorescence in situ hybridization to map the AZGP1 gene to 7q22.
Freije et al. (1993) found that the AZGP1 gene spans over 9.7 kb and that its overall organization and nucleotide sequence resemble those of the first 4 exons of class I MHC genes (see 142800). However, it differs from those genes by its lack of coding information for transmembrane and cytoplasmic domains typical of MHC genes, which is consistent with its presence as a soluble protein in various physiologic and pathologic fluids. In addition, it contains a high density of repetitive sequences, including Alu, MER, and MIR elements, which are not present at equivalent positions in class I MHC genes. The human genome also contains a putative AZGP1 pseudogene.
Ueyama et al. (1993) isolated the functional gene and found it to be 9.3 kb long and composed of 4 exons. The first exon codes for the 5-prime untranslated region, the signal sequence, and the first 6 amino acids. The second exon codes for domain A, the third for domain B, and the fourth for domain C and the 3-prime untranslated region. Ueyama et al. (1993) also isolated 2 pseudogenes retaining exon-intron organization.
Freije et al. (1991) studied the expression of this protein in benign and malignant breast tissues.
Freije et al. (1993) suggested that in light of the lack of polymorphism in the AZGP1 gene in comparison with MHC genes, this human glycoprotein may have a role in the transport of nonpolymorphic substances or in intercellular recognition processes.
Nakayashiki and Katsura (1989) studied ZAG in plasma by polyacrylamide gel isoelectric focusing followed by immunoblotting with specific antiserum to ZAG in the Japanese population. Most of 1,224 plasma samples showed a common, single-band pattern, whereas 16 samples showed variant double-band patterns which were classified into 4 types. The desialyzed form of ZAG commonly showed the single band. Differences in ZAG phenotypes appeared to be due to amino acid substitutions of the ZAG molecule. Nakayashiki and Katsura (1989) proposed the existence of 5 alleles, designated ZAG*1, ZAG*2, ZAG*3, ZAG*4 and ZAG*5, with frequencies of 0.9935, 0.0025, 0.0016, 0.0004, and 0.0020, respectively. The codominant transmission of the rare alleles ZAG*3 and ZAG*4 was confirmed in family studies.
Araki, T., Gejyo, F., Takagaki, K., Haupt, H., Schwick, H. G., Burgi, W., Marti, T., Schaller, J., Rickli, E., Brossmer, R., Atkinson, P. H., Putnam, F. W., Schmid, K. Complete amino acid sequence of human plasma Zn-alpha(2)-glycoprotein and its homology to histocompatibility antigens. Proc. Nat. Acad. Sci. 85: 679-683, 1988. [PubMed: 3422450] [Full Text: https://doi.org/10.1073/pnas.85.3.679]
Burgi, W., Schmid, K. Preparation and properties of Zn-alpha(2)-glycoprotein of normal human plasma. J. Biol. Chem. 236: 1066-1074, 1961. [PubMed: 13689030]
Freije, J. P., Fueyo, A., Uria, J. A., Velasco, G., Sanchez, L. M., Lopez-Boado, Y. S., Lopez-Otin, 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: 575-587, 1993. [PubMed: 8307568] [Full Text: https://doi.org/10.1016/s0888-7543(05)80359-3]
Freije, J. P., Fueyo, A., Uria, J., Lopez-Otin, C. Human Zn-alpha-2-glycoprotein cDNA cloning and expression analysis in benign and malignant breast tissues. FEBS Lett. 290: 247-249, 1991. [PubMed: 1915885] [Full Text: https://doi.org/10.1016/0014-5793(91)81271-9]
Kamboh, M. I., Ferrell, R. E. Genetic studies of low-abundance human plasma proteins. I. Microheterogeneity of zinc-alpha(2)-glycoprotein in biological fluids. Biochem. Genet. 24: 849-857, 1986. [PubMed: 3541891] [Full Text: https://doi.org/10.1007/BF00554524]
Nakayashiki, N., Katsura, S. Four variants of human plasma Zn-alpha(2)-glycoprotein (ZAG) in the Japanese population. Hum. Genet. 82: 293-295, 1989. [PubMed: 2731941] [Full Text: https://doi.org/10.1007/BF00291176]
Pendas, A. M., Matilla, T., Uria, J. A., Freije, J. P., Fueyo, A., Estivill, X., Lopez-Otin, C. Mapping of the human Zn-alpha-2-glycoprotein gene (AZGP1) to chromosome 7q22 by in situ hybridization. Cytogenet. Cell Genet. 66: 263-266, 1994. [PubMed: 8162703] [Full Text: https://doi.org/10.1159/000133708]
Ueyama, H., Deng, H.-X., Ohkubo, I. Molecular cloning and chromosomal assignment of the gene for human Zn-alpha-2-glycoprotein. Biochemistry 32: 12968-12976, 1993. [PubMed: 8241150] [Full Text: https://doi.org/10.1021/bi00211a004]
Ueyama, H., Niwa, M., Tada, T., Sasaki, M., Ohkubo, I. Cloning and nucleotide sequence of a human Zn-alpha(2)-glycoprotein cDNA and chromosomal assignment of its gene. Biochem. Biophys. Res. Commun. 177: 696-703, 1991. [PubMed: 2049092] [Full Text: https://doi.org/10.1016/0006-291x(91)91844-3]