title: Structure of the human liver/bone/kidney alkaline phosphatase gene.
abstract: 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.
authors.affiliation: Department of Human Genetics, University of Pennsylvania School of Medicine, Philadelphia 19104.
authors.forename: M J
authors.initials: MJ
authors.lastname: Weiss
authors.forename: K
authors.initials: K
authors.lastname: Ray
authors.forename: P S
authors.initials: PS
authors.lastname: Henthorn
authors.forename: B
authors.initials: B
authors.lastname: Lamb
authors.forename: T
authors.initials: T
authors.lastname: Kadesch
authors.forename: H
authors.initials: H
authors.lastname: Harris
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics*; D001483:Base Sequence; D005075:Biological Evolution; D001842:Bone and Bones / Q000201:enzymology*; D004247:DNA / Q000235:genetics; D004274:DNA, Recombinant; D005091:Exons; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D007438:Introns; D007668:Kidney / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D012516:Osteosarcoma / Q000201:enzymology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D004274:DNA, Recombinant; D012333:RNA, Messenger; D004247:DNA; D000469:Alkaline Phosphatase