Molecular cloning and chromosomal assignment of the gene for human zinc-.alpha.2-glycoprotein

Genomic clones containing the human Zn-alpha 2-glycoprotein gene were isolated. Two of them were for the functional gene overlapped, and the other four were for two different pseudogenes (1 and 2) retaining exon-intron organization. The complete DNA sequence of the functional gene (9.3 kb) and its 5'- and 3'-flanking regions (5.3 and 0.1 kb, respectively) was determined. The gene is composed of four exons; the first exon is for the 5'-untranslated region, the signal sequence, and the first six amino acids; the second, for domain A; the third, for domain B; and the fourth, for domain C and the 3'-untranslated region. The 5'-flanking region contains a TATA box, a CAT box, an octamer sequence, and three possible Spl-binding sites. Ten and three copies of Alu repetitive DNA were identified within the gene and the 5'-flanking region, respectively, and they occupy 30% of the gene. The nucleotide sequences around the exons of pseudogene 1 were also determined; they had high homology (90-91%) with the corresponding region of the functional gene. Southern blot analysis suggested that there are only three genes, including nonfunctional ones, for Zn-alpha 2-glycoprotein in humans. The gene (ZA2G) was mapped to human chromosome band 7q22.1 by fluorescence in situ hybridization.