title: Structure-function analysis of factor VII activating protease (FSAP): sequence determinants for heparin binding and cellular functions.
abstract: Factor VII activating protease (FSAP) is associated with cardiovascular diseases and liver fibrosis. To understand the regulation of its proteolytic activity we have characterized recombinant FSAP-mutants over-expressed in HEK-293 cells. The secreted FSAP-protein concentration correlated inversely with the enzymatic activity of the FSAP-mutants. Over-expression of enzymatically active FSAP decreased cell viability, whereas inactive variants were expressed and secreted in adequate amounts. The naturally occurring G534E-variant exhibited reduced proteolytic activity. The DeltaEGF-3 mutant showed diminished binding to and activation by heparin. Hence, regulation of FSAP activity is dependent on its EGF-3 domain and over-expression of active variants induces cell death.
authors.affiliation: Institute for Biochemistry, Medical School, Justus-Liebig-University Giessen, Giessen, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Muhl
authors.forename: Karin
authors.initials: K
authors.lastname: Hersemeyer
authors.forename: Klaus T
authors.initials: KT
authors.lastname: Preissner
authors.forename: Thomas
authors.initials: T
authors.lastname: Weimer
authors.forename: Sandip M
authors.initials: SM
authors.lastname: Kanse
mesh_terms: D020134:Catalytic Domain / Q000235:genetics; D002460:Cell Line; D015870:Gene Expression; D014644:Genetic Variation; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D016297:Mutagenesis, Site-Directed; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D011994:Recombinant Proteins; D006493:Heparin; C433550:HABP2 protein, human; D012697:Serine Endopeptidases