Structure of the human liver/bone/kidney alkaline phosphatase gene

• Published in: The Journal of biological chemistry 1988-08, Vol.263 (24), p.12002-12010
• Main Authors: Weiss, M J, Ray, K, Henthorn, P S, Lamb, B, Kadesch, T, Harris, H
• Format: Article
• Language: English
• Subjects: Alkaline Phosphatase - genetics; Base Sequence; Biological and medical sciences; Biological Evolution; Bone and Bones - enzymology; DNA - genetics; DNA, Recombinant; Exons; Fibroblasts - enzymology; Fundamental and applied biological sciences. Psychology; Genes. Genome; Humans; Introns; Kidney - enzymology; Liver - enzymology; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Nucleic Acid Hybridization; Osteosarcoma - enzymology; Promoter Regions, Genetic; RNA, Messenger - genetics; Transcription, Genetic; Tumor Cells, Cultured
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)37885-2

In man, there are multiple forms of alkaline phosphatase encoded by at least three homologous genes: placental, intestinal, and liver/bone/kidney. This report describes the characterization of the human liver/bone/kidney alkaline phosphatase locus. The gene appears to exist as a single copy in the haploid genome and is comprised of 12 exons distributed over more than 50 kilobases. In liver, kidney, SAOS-2 human osteosarcoma cells, and cultured fibroblasts, there is a single major start for transcription situated about 25 nucleotides downstream of an A/T-rich motif. The promoter region is extremely G/C-rich, is relatively abundant in the dinucleotide CpG, and contains four copies of the consensus sequence for SP1 binding (GGGCGG). The liver/bone/kidney alkaline phosphatase gene is at least five times larger than the intestinal and placental alkaline phosphatase genes, mainly due to intron size differences. Intron-exon junctions occur at analogous positions in all three genes, but there is an extra non-coding exon at the 5′ end of the liver/bone/kidney alkaline phosphatase gene. The relevance of our findings with respect to the evolution of the human alkaline phosphatase multigene family is discussed.