Molecular analysis of the gene for vitamin K dependent protein S and its pseudogene. Cloning and partial gene organization

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Abstract

Protein S is a vitamin K dependent plasma protein and a cofactor to activated protein C, a serine protease that regulates blood coagulation. The haploid genome contains two protein S genes (alpha and beta) with the protein S alpha-gene corresponding to the cloned cDNA. We have now isolated and mapped overlapping genomic clones that cover an area of 50 kilobases of the protein S alpha-gene which code for the 3' part of the gene, i.e., the thrombin-sensitive region, the four domains that are homologous to the epidermal growth factor (EGF) precursor, the COOH-terminal part of protein S that is homologous to a plasma sex hormone binding globulin (SHBG), and, finally, the 3' untranslated region. The thrombin-sensitive region and the EGF-like domains are each coded on a separate exon. The sizes of the exons coding for the COOH-terminal half of protein S and the location of the introns are nearly identical with those in the homologous SHBG gene. Furthermore, the phase class of the splice junctions is the same in these two genes. We have also isolated and mapped genomic clones that cover 25 kilobases of the protein S beta-gene, which was found to contain stop codons and a 2 bp deletion which introduces a frame shift, suggesting that it is a pseudogene. The structure of the two protein S genes and a comparison with the vitamin K dependent clotting factors support a model for their origin by exon shuffling and recruitment of the 3' part of the gene from an ancestor shared with the sex hormone binding globulin.

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Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medicinal Chemistry
  • Clinical Medicine

Keywords

  • Protein S, Phylogeny, Molecular Sequence Data, Introns, Humans, Glycoproteins/*genetics, Genomic Library, *Exons, DNA/chemistry, Molecular, Cloning, Amino Acid Sequence, Southern, Blotting, *Pseudogenes, Research Support, Non-U.S. Gov't, Sequence Homology, Nucleic Acid, Sex Hormone-Binding Globulin/*genetics, Vitamin K/*metabolism
Original languageEnglish
Pages (from-to)7861-8
JournalBiochemistry
Volume29
Issue number34
Publication statusPublished - 1990
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

34 The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Clinical Chemistry, Malmö (013016000), Emergency medicine/Medicine/Surgery (013240200)