Advanced

Localization of thrombin cleavage sites in the amino-terminal region of bovine protein S

Dahlbäck, Björn LU ; Lundwall, Åke LU and Stenflo, Johan LU (1986) In J Biol Chem 261(11). p.5-5111
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Peptide Fragments/isolation & purification/*metabolism, Glycoproteins/*metabolism, Endopeptidases/metabolism, Disulfides/metabolism, Cyanogen Bromide, Chymotrypsin/metabolism, Cattle, Calcium/metabolism, Amino Acid Sequence, Animals, Protein S, Research Support, Non-U.S. Gov't, *Serine Endopeptidases, Thrombin/*metabolism
in
J Biol Chem
volume
261
issue
11
pages
5 - 5111
external identifiers
  • Scopus:0023037785
language
English
LU publication?
yes
id
a23b8a54-6d66-4df1-942f-141db5bc048b (old id 3965130)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2937785
date added to LUP
2013-08-11 18:37:40
date last changed
2016-04-16 11:40:57
@misc{a23b8a54-6d66-4df1-942f-141db5bc048b,
  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.},
  author       = {Dahlbäck, Björn and Lundwall, Åke and Stenflo, Johan},
  keyword      = {Peptide Fragments/isolation & purification/*metabolism,Glycoproteins/*metabolism,Endopeptidases/metabolism,Disulfides/metabolism,Cyanogen Bromide,Chymotrypsin/metabolism,Cattle,Calcium/metabolism,Amino Acid Sequence,Animals,Protein S,Research Support,Non-U.S. Gov't,*Serine Endopeptidases,Thrombin/*metabolism},
  language     = {eng},
  number       = {11},
  pages        = {5--5111},
  series       = {J Biol Chem},
  title        = {Localization of thrombin cleavage sites in the amino-terminal region of bovine protein S},
  volume       = {261},
  year         = {1986},
}