| 1. |
- Dahlbäck, Björn, et al.
(författare)
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Assignment of gene for coagulation factor V to chromosome 1 in man and to chromosome 13 in rat
- 1988
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Ingår i: Somatic Cell and Molecular Genetics. - 0740-7750. ; 14:5, s. 14-509
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Tidskriftsartikel (refereegranskat)abstract
- Two different factor V cDNA fragments were used as hydridization probes in the chromosomal assignment of the human and rat factor V genes. A 1.6-kb EcoRI fragment was used as a hybridization probe to analyze a panel of human-rodent somatic cell hybrids. Cosegregation of factor V specific DNA restriction fragments with human chromosome 1 was observed. In addition, a panel of rat-mouse somatic cell hybrids was analyzed with another human factor V cDNA probe to localize the gene for rat coagulation factor V. In the rat, the gene for coagulation factor V was found to be located in chromosome 13. This is the first gene in the rat to be localized to chromosome 13.
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| 2. |
- Dahlbäck, Björn, et al.
(författare)
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Localization of thrombin cleavage sites in the amino-terminal region of bovine protein S
- 1986
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Ingår i: Journal of Biological Chemistry. - 0021-9258. ; 261:11, s. 5-5111
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Tidskriftsartikel (refereegranskat)abstract
- Protein S is a vitamin K-dependent plasma protein. It functions as a cofactor to activated protein C in the inactivation of factors Va and VIIIa by limited proteolysis. Protein S is very sensitive to proteolysis by thrombin which reduces its calcium ion binding and leads to a loss of its cofactor activity. We have now determined the sequence of the 100 amino-terminal amino acid residues and localized the thrombin cleavage sites. Protein S contains 11 gamma-carboxyglutamic acid residues in the amino-terminal region (residues 1-36). This part of protein S is highly homologous to the corresponding parts in the other vitamin K-dependent clotting factors, whereas the region between residues 45 and 75 is not at all homologous to the other clotting factors. Thrombin cleaves two peptide bonds in this part of protein S, first at arginine 70 and then at arginine 52. The peptide containing residues 53-70 is released from protein S after thrombin cleavage. The amino-terminal fragment, residues 1-52, is linked to the large carboxyl-terminal fragment by a disulfide bond, which involves cysteine 47. After residue 78, protein S is again homologous to factors IX and X and to proteins C and Z, but not to prothrombin. Position 95 is occupied by a beta-hydroxyaspartic acid residue.
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| 3. |
- Dahlbäck, Björn, et al.
(författare)
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Primary structure of bovine vitamin K-dependent protein S
- 1986
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Ingår i: Proc Natl Acad Sci U S A. ; 83:12, s. 203-4199
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Tidskriftsartikel (refereegranskat)abstract
- Protein S is a vitamin K-dependent plasma protein that functions as a cofactor to activated protein C in the inactivation of coagulation factors Va and VIIIa. The nucleotide sequence of a full-length cDNA clone, obtained from a bovine liver library, was determined and the amino acid sequence was deduced. In addition, 95% of the structure was determined by protein sequencing. Protein S consists of 634 amino acids in a single polypeptide chain and has one asparagine-linked carbohydrate side chain. The cDNA sequence showed that the protein has a leader sequence, 41 amino acid residues long. The amino-terminal part of the molecule containing gamma-carboxyglutamic acid is followed by a region, residues 42-75, with two peptide bonds that are very sensitive to cleavage by thrombin. Residues 76-244 have four cysteinerich repeat sequences, each about 40 residues long, that are homologous to the precursor of mouse epidermal growth factor. In contrast to the other vitamin K-dependent plasma proteins, the carboxyl-terminal part of protein S is not homologous to the serine proteases.
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| 4. |
- Stenflo, Johan, et al.
(författare)
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beta-Hydroxyasparagine in domains homologous to the epidermal growth factor precursor in vitamin K-dependent protein S
- 1987
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Ingår i: Proc Natl Acad Sci U S A. ; 84:2, s. 72-368
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin K-dependent protein S is involved in the regulation of blood coagulation. It is a 75-kDa single chain protein with an NH2-terminal gamma-carboxyglutamic acid-containing domain followed by a thrombin-sensitive region and four domains arranged in tandem, each of which is homologous to the epidermal growth factor (EGF) precursor. The NH2-terminal EGF-like domain contains beta-hydroxyaspartic acid, which has been identified in vitamin K-dependent proteins. The following EGF-like repeat has a very pronounced sequence homology (10 consecutive residues identical) to one of the EGF-like units in the EGF precursor. We now show that, in protein S, this EGF-like repeat has one beta-hydroxyasparagine residue formed by hydroxylation of asparagine. The two COOH-terminal EGF-like repeats also contain beta-hydroxyasparagine, an amino acid not previously found in proteins. Sequence comparisons have enabled us to identify a consensus sequence that seems to be required by the hydroxylase(s).
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