title: Characterization of the human gene for a polypeptide that acts both as the beta subunit of prolyl 4-hydroxylase and as protein disulfide isomerase.
abstract: A single polypeptide acts as the beta subunit of prolyl 4-hydroxylase and the enzyme protein disulfide isomerase and may also function as a cellular thyroid hormone binding protein. We report here that the human gene for this polypeptide is about 18 kilobase pairs and consists of 11 exons. The two thioredoxin-like regions are coded by exons 1-2 and 8-9, respectively. The codons for the two presumed active sites of protein disulfide isomerase, each a Cys-Gly-His-Cys sequence, are located 12 base pairs from the beginning of exons 2 and 9. The last 3 amino acids coded by exons 1 and 8 and the first 9 amino acids coded by exons 2 and 9, including a broken codon for Tyr, are identical in the respective exon-intron junctions. These regions are also highly homologous to the active sites of bacterial thioredoxins. The data suggest that evolution of this gene has involved exon shuffling and duplication of a two-exon unit, in which the internal exon-intron junctions have been entirely conserved. The region between exons 1-2 and 8-9 appears to contain other duplications. The 5' flanking sequences contain a TATA box, six CCAAT boxes, and other elements which may be involved in regulation of the cellular amounts of this polypeptide.
authors.affiliation: Biocenter, University of Oulu, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Tasanen
authors.forename: T
authors.initials: T
authors.lastname: Parkkonen
authors.forename: L T
authors.initials: LT
authors.lastname: Chow
authors.forename: K I
authors.initials: KI
authors.lastname: Kivirikko
authors.forename: T
authors.initials: T
authors.lastname: Pihlajaniemi
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D003360:Cosmids; D005796:Genes; D006801:Humans; D007535:Isomerases / Q000235:genetics*; D046911:Macromolecular Substances; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics; D011393:Procollagen-Proline Dioxygenase / Q000235:genetics*; D019704:Protein Disulfide-Isomerases; D015183:Restriction Mapping
chemical_list: D046911:Macromolecular Substances; D010455:Peptides; D011393:Procollagen-Proline Dioxygenase; D007535:Isomerases; D019704:Protein Disulfide-Isomerases