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

Edenbrandt, Carl-Magnus LU ; Lundwall, Åke LU ; Wydro, R. and Stenflo, J. (1990) In Biochemistry 29(34). p.7861-8
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
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
in
Biochemistry
volume
29
issue
34
pages
7861 - 8
publisher
The American Chemical Society
external identifiers
  • Scopus:0025182946
ISSN
0006-2960
language
English
LU publication?
yes
id
81a9cc29-567c-4742-90ea-1097c9fb36b7 (old id 3965198)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2148112
date added to LUP
2013-08-11 18:39:59
date last changed
2016-04-16 12:28:10
@misc{81a9cc29-567c-4742-90ea-1097c9fb36b7,
  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.},
  author       = {Edenbrandt, Carl-Magnus and Lundwall, Åke and Wydro, R. and Stenflo, J.},
  issn         = {0006-2960},
  keyword      = {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},
  language     = {eng},
  number       = {34},
  pages        = {7861--8},
  publisher    = {ARRAY(0x7e57158)},
  series       = {Biochemistry},
  title        = {Molecular analysis of the gene for vitamin K dependent protein S and its pseudogene. Cloning and partial gene organization},
  volume       = {29},
  year         = {1990},
}