The formation of a fibrin clot at the site of an injury to the wall of a normal blood vessel is an essential part of the process to stop blood loss after vascular injury. The reactions that lead to fibrin clot formation are commonly described as a cascade, in which the product of each step is an enzyme or cofactor needed for following reactions to proceed efficiently. The entire clotting cascade can be divided into three portions, the extrinsic pathway, the intrinsic pathway, and the common pathway. The extrinsic pathway begins with the release of tissue factor at the site of vascular injury and leads to the activation of factor X. The intrinsic pathway provides an alternative mechanism for activation of factor X, starting from the activation of factor XII. The common pathway consists of the steps linking the activation of factor X to the formation of a multimeric, cross-linked fibrin clot. Each of these pathways includes not only a cascade of events that generate the catalytic activities needed for clot formation, but also numerous positive and negative regulatory events. <a href=http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=140877>View original pathway at Reactome</a> d54 f7b d54 f7b bb6 c4a da1 da1 bb6 c4a da1 a14 da1 e58 a14 d54 f7b d54 f7b d54 f7b d54 f7b d54 f7b e8a fe8 e8a e8a e8a fe8 e8a d54 f7b d54 f7b bb6 c4a da1 a14 e5d d4a e5d d4a e8a fe8 e0c e5d d4a e0c d4a bb6 c4a da1 a14 da1 e58 ed6 b3d ed5 ed6 b3d ed5 bb6 c4a da1 a14 ed6 b3d ed5 ed6 b3d ed5 e58 Fibrinogen is a hexamer, containing two fibrinogen alpha chains, two fibrinogen beta chains, and two fibrinogen gamma chains, held together by disulfide bonds. Fibrinogen is a hexamer, containing two fibrinogen alpha chains, two fibrinogen beta chains, and two fibrinogen gamma chains, held together by disulfide bonds. Fibrin is a hexamer of two fibrinogen alpha chains, two fibrinogen beta chains, and two fibrinogen gamma chains, held together by disulfide bonds. It is formed in vivo by the thrombin-catalyzed removal of amino terminal fibinopeptides from the A alpha and B beta chains of fibrinogen. This fibrin hexamer ("fibrin monomer") is the subunit that multimerizes to form a fibrin clot ("fibrin multimer"). Fibrin is a hexamer of two fibrinogen alpha chains, two fibrinogen beta chains, and two fibrinogen gamma chains, held together by disulfide bonds. It is formed in vivo by the thrombin-catalyzed removal of amino terminal fibinopeptides from the A alpha and B beta chains of fibrinogen. This fibrin hexamer ("fibrin monomer") is the subunit that multimerizes to form a fibrin clot ("fibrin multimer"). The fibrin "monomers" formed by the action of thrombin on fibrinogen associate spontaneously into multimers. This association can follow several distinct pathways and may be able to form several types of higher-order structures. All of these possibilities are represented in Reactome as a fibrin trimer. The fibrin "monomers" formed by the action of thrombin on fibrinogen associate spontaneously into multimers. This association can follow several distinct pathways and may be able to form several types of higher-order structures. All of these possibilities are represented in Reactome as a fibrin trimer. b23 add add c93 add c93 c28 c28 c28 e5d d4a e5d d4a a42 a42 da7 e35 a11 fe8 a11 e35 a11 e35 a11 e35 f3b e35 a11 fe8 a11 e35 f3b a11 e35 f3b ed6 b3d ed5 e35 a11 fe8 a11 e35 a11 e35 d16 Tissue factor sequestered in the wall of a blood vessel is exposed to circulating blood when the endothelial lining of the vessel is injured. Tissue factor sequestered in the wall of a blood vessel is exposed to circulating blood when the endothelial lining of the vessel is injured. ec8 Tissue factor exposed at the endothelial cell surface forms a complex with factor VII from plasma. Tissue factor exposed at the endothelial cell surface forms a complex with factor VII from plasma. a92 Tissue factor exposed at the endothelial cell surface forms a complex with factor VII from plasma. Tissue factor exposed at the endothelial cell surface forms a complex with factor VII from plasma. a92 Tissue factor exposed at the endothelial cell surface forms a complex with factor VII from plasma. Tissue factor exposed at the endothelial cell surface forms a complex with factor VII from plasma. a92 Factor VII, bound to tissue factor at the endothelial cell surface, catalyzes the activation of factor X from plasma with moderate efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) Factor VII, bound to tissue factor at the endothelial cell surface, catalyzes the activation of factor X from plasma with moderate efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) d57 a92 cd2 Factor VII, bound to tissue factor at the endothelial cell surface, catalyzes the activation of factor X from plasma with moderate efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) Factor VII, bound to tissue factor at the endothelial cell surface, catalyzes the activation of factor X from plasma with moderate efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) d57 a92 cd2 Factor VII, bound to tissue factor at the endothelial cell surface, catalyzes the activation of factor X from plasma with moderate efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) Factor VII, bound to tissue factor at the endothelial cell surface, catalyzes the activation of factor X from plasma with moderate efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) d57 a92 cd2 Factor VII, bound to tissue factor at the endothelial cell surface, catalyzes the activation of factor X from plasma with moderate efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) Factor VII, bound to tissue factor at the endothelial cell surface, catalyzes the activation of factor X from plasma with moderate efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) d57 a92 cd2 Factor Xa catalyzes the activation of factor VII from plasma. Factor Xa catalyzes the activation of factor VII from plasma. df0 Factor Xa catalyzes the activation of factor VII from plasma. Factor Xa catalyzes the activation of factor VII from plasma. df0 Tissue factor exposed at the endothelial cell surface forms a complex with F7a (activated factor VII) from the plasma Tissue factor exposed at the endothelial cell surface forms a complex with F7a (activated factor VII) from the plasma ed3 Tissue factor exposed at the endothelial cell surface forms a complex with F7a (activated factor VII) from the plasma Tissue factor exposed at the endothelial cell surface forms a complex with F7a (activated factor VII) from the plasma ed3 Tissue factor exposed at the endothelial cell surface forms a complex with F7a (activated factor VII) from the plasma Tissue factor exposed at the endothelial cell surface forms a complex with F7a (activated factor VII) from the plasma ed3 Factor VIIa, bound to tissue factor at the endothelial cell surface (the "extrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) Factor VIIa, bound to tissue factor at the endothelial cell surface (the "extrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) baa d57 d46 Factor VIIa, bound to tissue factor at the endothelial cell surface (the "extrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) Factor VIIa, bound to tissue factor at the endothelial cell surface (the "extrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) baa d57 d46 Factor VIIa, bound to tissue factor at the endothelial cell surface (the "extrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) Factor VIIa, bound to tissue factor at the endothelial cell surface (the "extrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) baa d57 d46 Factor VIIa, bound to tissue factor at the endothelial cell surface (the "extrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) Factor VIIa, bound to tissue factor at the endothelial cell surface (the "extrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) baa d57 d46 Factor VIIa, bound to tissue factor at the endothelial cell surface (the "extrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) Factor VIIa, bound to tissue factor at the endothelial cell surface (the "extrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) baa d57 d46 Factor VIIa, bound to tissue factor at the endothelial cell surface (the "extrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) Factor VIIa, bound to tissue factor at the endothelial cell surface (the "extrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) baa d57 d46 Factor VIIa, bound to tissue factor at the endothelial cell surface, catalyzes the formation of activated factor IX with high efficiency. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.) Factor VIIa, bound to tissue factor at the endothelial cell surface, catalyzes the formation of activated factor IX with high efficiency. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.) ed4 baa Factor VIIa, bound to tissue factor at the endothelial cell surface, catalyzes the formation of activated factor IX with high efficiency. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.) Factor VIIa, bound to tissue factor at the endothelial cell surface, catalyzes the formation of activated factor IX with high efficiency. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.) ed4 baa Factor VIIa, bound to tissue factor at the endothelial cell surface, catalyzes the formation of activated factor IX with high efficiency. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.) Factor VIIa, bound to tissue factor at the endothelial cell surface, catalyzes the formation of activated factor IX with high efficiency. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.) ed4 baa Factor VIIa, bound to tissue factor at the endothelial cell surface, catalyzes the formation of activated factor IX with high efficiency. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.) Factor VIIa, bound to tissue factor at the endothelial cell surface, catalyzes the formation of activated factor IX with high efficiency. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.) ed4 baa TFPI binds to the factor VIIa:TF complex and to factor Xa at the endothelial surface, forming a stable heterotetrameric complex in which factor VIIa is catalytically inactive. TFPI binds to the factor VIIa:TF complex and to factor Xa at the endothelial surface, forming a stable heterotetrameric complex in which factor VIIa is catalytically inactive. e5a TFPI binds to the factor VIIa:TF complex and to factor Xa at the endothelial surface, forming a stable heterotetrameric complex in which factor VIIa is catalytically inactive. TFPI binds to the factor VIIa:TF complex and to factor Xa at the endothelial surface, forming a stable heterotetrameric complex in which factor VIIa is catalytically inactive. e5a TFPI binds to the factor VIIa:TF complex and to factor Xa at the endothelial surface, forming a stable heterotetrameric complex in which factor VIIa is catalytically inactive. TFPI binds to the factor VIIa:TF complex and to factor Xa at the endothelial surface, forming a stable heterotetrameric complex in which factor VIIa is catalytically inactive. e5a TFPI binds to the factor VIIa:TF complex and to factor Xa at the endothelial surface, forming a stable heterotetrameric complex in which factor VIIa is catalytically inactive. TFPI binds to the factor VIIa:TF complex and to factor Xa at the endothelial surface, forming a stable heterotetrameric complex in which factor VIIa is catalytically inactive. e5a Kininogen (high molecular weight kininogen; HK) associates with C1q binding protein on the cell surface in a reaction dependent on Zn++ (Joseph et al. 1996). In the body, the Zn++ needed to drive this reaction may be provided locally by Zn++ release from activated platelets (Mahdi et al. 2002). The C1q binding protein is inferred to form tetramers based on the properties of purified recombinant protein in vitro (Ghebrehiwet et al. 1994); the stoichiometry of the cell surface complex has not been determined directly. Kininogen (high molecular weight kininogen; HK) associates with C1q binding protein on the cell surface in a reaction dependent on Zn++ (Joseph et al. 1996). In the body, the Zn++ needed to drive this reaction may be provided locally by Zn++ release from activated platelets (Mahdi et al. 2002). The C1q binding protein is inferred to form tetramers based on the properties of purified recombinant protein in vitro (Ghebrehiwet et al. 1994); the stoichiometry of the cell surface complex has not been determined directly. cd9 a1e dab f42 Kininogen (high molecular weight kininogen; HK) associates with C1q binding protein on the cell surface in a reaction dependent on Zn++ (Joseph et al. 1996). In the body, the Zn++ needed to drive this reaction may be provided locally by Zn++ release from activated platelets (Mahdi et al. 2002). The C1q binding protein is inferred to form tetramers based on the properties of purified recombinant protein in vitro (Ghebrehiwet et al. 1994); the stoichiometry of the cell surface complex has not been determined directly. Kininogen (high molecular weight kininogen; HK) associates with C1q binding protein on the cell surface in a reaction dependent on Zn++ (Joseph et al. 1996). In the body, the Zn++ needed to drive this reaction may be provided locally by Zn++ release from activated platelets (Mahdi et al. 2002). The C1q binding protein is inferred to form tetramers based on the properties of purified recombinant protein in vitro (Ghebrehiwet et al. 1994); the stoichiometry of the cell surface complex has not been determined directly. cd9 a1e dab f42 Kininogen (high molecular weight kininogen; HK) associates with C1q binding protein on the cell surface in a reaction dependent on Zn++ (Joseph et al. 1996). In the body, the Zn++ needed to drive this reaction may be provided locally by Zn++ release from activated platelets (Mahdi et al. 2002). The C1q binding protein is inferred to form tetramers based on the properties of purified recombinant protein in vitro (Ghebrehiwet et al. 1994); the stoichiometry of the cell surface complex has not been determined directly. Kininogen (high molecular weight kininogen; HK) associates with C1q binding protein on the cell surface in a reaction dependent on Zn++ (Joseph et al. 1996). In the body, the Zn++ needed to drive this reaction may be provided locally by Zn++ release from activated platelets (Mahdi et al. 2002). The C1q binding protein is inferred to form tetramers based on the properties of purified recombinant protein in vitro (Ghebrehiwet et al. 1994); the stoichiometry of the cell surface complex has not been determined directly. cd9 a1e dab f42 Kininogen (high molecular weight kininogen; HK) associates with C1q binding protein on the cell surface in a reaction dependent on Zn++ (Joseph et al. 1996). In the body, the Zn++ needed to drive this reaction may be provided locally by Zn++ release from activated platelets (Mahdi et al. 2002). The C1q binding protein is inferred to form tetramers based on the properties of purified recombinant protein in vitro (Ghebrehiwet et al. 1994); the stoichiometry of the cell surface complex has not been determined directly. Kininogen (high molecular weight kininogen; HK) associates with C1q binding protein on the cell surface in a reaction dependent on Zn++ (Joseph et al. 1996). In the body, the Zn++ needed to drive this reaction may be provided locally by Zn++ release from activated platelets (Mahdi et al. 2002). The C1q binding protein is inferred to form tetramers based on the properties of purified recombinant protein in vitro (Ghebrehiwet et al. 1994); the stoichiometry of the cell surface complex has not been determined directly. cd9 a1e dab f42 Prekallikrein (PK) associates specifically with kininogen (HK) on cell surfaces. In vivo, this reaction may occur primarily on the surfaces of endothelial cells in response to platelet activation (Lin et al. 1997; Motta et al. 1998; Mahdi et al. 2003). Prekallikrein (PK) associates specifically with kininogen (HK) on cell surfaces. In vivo, this reaction may occur primarily on the surfaces of endothelial cells in response to platelet activation (Lin et al. 1997; Motta et al. 1998; Mahdi et al. 2003). aa7 f84 a08 ae0 Prekallikrein (PK) associates specifically with kininogen (HK) on cell surfaces. In vivo, this reaction may occur primarily on the surfaces of endothelial cells in response to platelet activation (Lin et al. 1997; Motta et al. 1998; Mahdi et al. 2003). Prekallikrein (PK) associates specifically with kininogen (HK) on cell surfaces. In vivo, this reaction may occur primarily on the surfaces of endothelial cells in response to platelet activation (Lin et al. 1997; Motta et al. 1998; Mahdi et al. 2003). aa7 f84 a08 ae0 Prekallikrein (PK) associates specifically with kininogen (HK) on cell surfaces. In vivo, this reaction may occur primarily on the surfaces of endothelial cells in response to platelet activation (Lin et al. 1997; Motta et al. 1998; Mahdi et al. 2003). Prekallikrein (PK) associates specifically with kininogen (HK) on cell surfaces. In vivo, this reaction may occur primarily on the surfaces of endothelial cells in response to platelet activation (Lin et al. 1997; Motta et al. 1998; Mahdi et al. 2003). aa7 f84 a08 ae0 Prekallikrein in a complex with kininogen and C1q binding protein on the plasma membrane is cleaved to generate active kallikrein, which remains bound to the complex. In the body, this reaction appears to occur on the surfaces of endothelial cells and may require the presence of activated platelets. Recent work indicates that the protease that cleaves prekallikrein under these conditions is prolylcarboxypeptidase. Although this enzyme was originally isolated from lysosomes (Odya et al. 1978; Tan et al. 1993), it is associated with plasma membranes of cultured human endothelial cells in vitro (Moreira et al. 2002; Shariat-Madar et al. 2002), and the purified recombinant enzyme efficiently cleaves prekallikrein (Shariat-Madar et al. 2004). In contrast factor XII, despite its activity on prekallikrein in vitro, appears not to be responsible for prekallikrein activation on the cell surface (Rojkjaer et al. 1998). Prekallikrein in a complex with kininogen and C1q binding protein on the plasma membrane is cleaved to generate active kallikrein, which remains bound to the complex. In the body, this reaction appears to occur on the surfaces of endothelial cells and may require the presence of activated platelets. Recent work indicates that the protease that cleaves prekallikrein under these conditions is prolylcarboxypeptidase. Although this enzyme was originally isolated from lysosomes (Odya et al. 1978; Tan et al. 1993), it is associated with plasma membranes of cultured human endothelial cells in vitro (Moreira et al. 2002; Shariat-Madar et al. 2002), and the purified recombinant enzyme efficiently cleaves prekallikrein (Shariat-Madar et al. 2004). In contrast factor XII, despite its activity on prekallikrein in vitro, appears not to be responsible for prekallikrein activation on the cell surface (Rojkjaer et al. 1998). eb9 b66 ffe e60 a1a Prekallikrein in a complex with kininogen and C1q binding protein on the plasma membrane is cleaved to generate active kallikrein, which remains bound to the complex. In the body, this reaction appears to occur on the surfaces of endothelial cells and may require the presence of activated platelets. Recent work indicates that the protease that cleaves prekallikrein under these conditions is prolylcarboxypeptidase. Although this enzyme was originally isolated from lysosomes (Odya et al. 1978; Tan et al. 1993), it is associated with plasma membranes of cultured human endothelial cells in vitro (Moreira et al. 2002; Shariat-Madar et al. 2002), and the purified recombinant enzyme efficiently cleaves prekallikrein (Shariat-Madar et al. 2004). In contrast factor XII, despite its activity on prekallikrein in vitro, appears not to be responsible for prekallikrein activation on the cell surface (Rojkjaer et al. 1998). Prekallikrein in a complex with kininogen and C1q binding protein on the plasma membrane is cleaved to generate active kallikrein, which remains bound to the complex. In the body, this reaction appears to occur on the surfaces of endothelial cells and may require the presence of activated platelets. Recent work indicates that the protease that cleaves prekallikrein under these conditions is prolylcarboxypeptidase. Although this enzyme was originally isolated from lysosomes (Odya et al. 1978; Tan et al. 1993), it is associated with plasma membranes of cultured human endothelial cells in vitro (Moreira et al. 2002; Shariat-Madar et al. 2002), and the purified recombinant enzyme efficiently cleaves prekallikrein (Shariat-Madar et al. 2004). In contrast factor XII, despite its activity on prekallikrein in vitro, appears not to be responsible for prekallikrein activation on the cell surface (Rojkjaer et al. 1998). eb9 b66 ffe e60 a1a The cleavage of kininogen (HK, high molecular weight kininogen) yields activated kininogen and the vasoactive peptide bradykinin (Kerbirou and Griffin 1979; Lottspeich et al. 1985; Kellerman et al. 1986). In vivo, this reaction is catalyzed by activated kallikrein, takes places within the kallikrein:kininogen:C1q binding protein tetramer complex on the endothelial cell surface, and results in the release of kallikrein and bradykinin (Motta et al. 1998). The hormonal functions of bradykinin will be annotated in a future version of Reactome. The cleavage of kininogen (HK, high molecular weight kininogen) yields activated kininogen and the vasoactive peptide bradykinin (Kerbirou and Griffin 1979; Lottspeich et al. 1985; Kellerman et al. 1986). In vivo, this reaction is catalyzed by activated kallikrein, takes places within the kallikrein:kininogen:C1q binding protein tetramer complex on the endothelial cell surface, and results in the release of kallikrein and bradykinin (Motta et al. 1998). The hormonal functions of bradykinin will be annotated in a future version of Reactome. f42 b5c d07 a08 The cleavage of kininogen (HK, high molecular weight kininogen) yields activated kininogen and the vasoactive peptide bradykinin (Kerbirou and Griffin 1979; Lottspeich et al. 1985; Kellerman et al. 1986). In vivo, this reaction is catalyzed by activated kallikrein, takes places within the kallikrein:kininogen:C1q binding protein tetramer complex on the endothelial cell surface, and results in the release of kallikrein and bradykinin (Motta et al. 1998). The hormonal functions of bradykinin will be annotated in a future version of Reactome. The cleavage of kininogen (HK, high molecular weight kininogen) yields activated kininogen and the vasoactive peptide bradykinin (Kerbirou and Griffin 1979; Lottspeich et al. 1985; Kellerman et al. 1986). In vivo, this reaction is catalyzed by activated kallikrein, takes places within the kallikrein:kininogen:C1q binding protein tetramer complex on the endothelial cell surface, and results in the release of kallikrein and bradykinin (Motta et al. 1998). The hormonal functions of bradykinin will be annotated in a future version of Reactome. f42 b5c d07 a08 The cleavage of kininogen (HK, high molecular weight kininogen) yields activated kininogen and the vasoactive peptide bradykinin (Kerbirou and Griffin 1979; Lottspeich et al. 1985; Kellerman et al. 1986). In vivo, this reaction is catalyzed by activated kallikrein, takes places within the kallikrein:kininogen:C1q binding protein tetramer complex on the endothelial cell surface, and results in the release of kallikrein and bradykinin (Motta et al. 1998). The hormonal functions of bradykinin will be annotated in a future version of Reactome. The cleavage of kininogen (HK, high molecular weight kininogen) yields activated kininogen and the vasoactive peptide bradykinin (Kerbirou and Griffin 1979; Lottspeich et al. 1985; Kellerman et al. 1986). In vivo, this reaction is catalyzed by activated kallikrein, takes places within the kallikrein:kininogen:C1q binding protein tetramer complex on the endothelial cell surface, and results in the release of kallikrein and bradykinin (Motta et al. 1998). The hormonal functions of bradykinin will be annotated in a future version of Reactome. f42 b5c d07 a08 The cleavage of kininogen (HK, high molecular weight kininogen) yields activated kininogen and the vasoactive peptide bradykinin (Kerbirou and Griffin 1979; Lottspeich et al. 1985; Kellerman et al. 1986). In vivo, this reaction is catalyzed by activated kallikrein, takes places within the kallikrein:kininogen:C1q binding protein tetramer complex on the endothelial cell surface, and results in the release of kallikrein and bradykinin (Motta et al. 1998). The hormonal functions of bradykinin will be annotated in a future version of Reactome. The cleavage of kininogen (HK, high molecular weight kininogen) yields activated kininogen and the vasoactive peptide bradykinin (Kerbirou and Griffin 1979; Lottspeich et al. 1985; Kellerman et al. 1986). In vivo, this reaction is catalyzed by activated kallikrein, takes places within the kallikrein:kininogen:C1q binding protein tetramer complex on the endothelial cell surface, and results in the release of kallikrein and bradykinin (Motta et al. 1998). The hormonal functions of bradykinin will be annotated in a future version of Reactome. f42 b5c d07 a08 The cleavage of kininogen (HK, high molecular weight kininogen) yields activated kininogen and the vasoactive peptide bradykinin (Kerbirou and Griffin 1979; Lottspeich et al. 1985; Kellerman et al. 1986). In vivo, this reaction is catalyzed by activated kallikrein, takes places within the kallikrein:kininogen:C1q binding protein tetramer complex on the endothelial cell surface, and results in the release of kallikrein and bradykinin (Motta et al. 1998). The hormonal functions of bradykinin will be annotated in a future version of Reactome. The cleavage of kininogen (HK, high molecular weight kininogen) yields activated kininogen and the vasoactive peptide bradykinin (Kerbirou and Griffin 1979; Lottspeich et al. 1985; Kellerman et al. 1986). In vivo, this reaction is catalyzed by activated kallikrein, takes places within the kallikrein:kininogen:C1q binding protein tetramer complex on the endothelial cell surface, and results in the release of kallikrein and bradykinin (Motta et al. 1998). The hormonal functions of bradykinin will be annotated in a future version of Reactome. f42 b5c d07 a08 Cleavage of a single peptide bond converts factor XII to activated factor XII (factor XIIa) (Fujikawa and McMullen 1983; McMullen and Fujikawa 1985). Identification of the catalytic activity or activities responsible for this cleavage has not been straightforward. Studies in vitro have demonstrated the autoactivation of factor XII as well as activation by kallikrein. Both reactions require the presence of negatively charged surfaces and are accelerated in the presence of kininogen (high molecular weight kininogen, HK) (Griffin and Cochrane 1976; Meier et al. 1977; Silverberg et al. 1980). Recent work suggests that factor XII activation in vivo may occur primarily on endothelial cell surfaces and that, as in vitro, association with kininogen may accelerate the reaction (Mahdi et al. 2002; Schmaier 2004), although alternative pathways and alternative mechanisms for associating factor XII with the cell surface have not been excluded (Joseph et al. 2001). Cleavage of a single peptide bond converts factor XII to activated factor XII (factor XIIa) (Fujikawa and McMullen 1983; McMullen and Fujikawa 1985). Identification of the catalytic activity or activities responsible for this cleavage has not been straightforward. Studies in vitro have demonstrated the autoactivation of factor XII as well as activation by kallikrein. Both reactions require the presence of negatively charged surfaces and are accelerated in the presence of kininogen (high molecular weight kininogen, HK) (Griffin and Cochrane 1976; Meier et al. 1977; Silverberg et al. 1980). Recent work suggests that factor XII activation in vivo may occur primarily on endothelial cell surfaces and that, as in vitro, association with kininogen may accelerate the reaction (Mahdi et al. 2002; Schmaier 2004), although alternative pathways and alternative mechanisms for associating factor XII with the cell surface have not been excluded (Joseph et al. 2001). ca9 cef b18 f54 fb9 fec dab c7a Cleavage of a single peptide bond converts factor XII to activated factor XII (factor XIIa) (Fujikawa and McMullen 1983; McMullen and Fujikawa 1985). Identification of the catalytic activity or activities responsible for this cleavage has not been straightforward. Studies in vitro have demonstrated the autoactivation of factor XII as well as activation by kallikrein. Both reactions require the presence of negatively charged surfaces and are accelerated in the presence of kininogen (high molecular weight kininogen, HK) (Griffin and Cochrane 1976; Meier et al. 1977; Silverberg et al. 1980). Recent work suggests that factor XII activation in vivo may occur primarily on endothelial cell surfaces and that, as in vitro, association with kininogen may accelerate the reaction (Mahdi et al. 2002; Schmaier 2004), although alternative pathways and alternative mechanisms for associating factor XII with the cell surface have not been excluded (Joseph et al. 2001). Cleavage of a single peptide bond converts factor XII to activated factor XII (factor XIIa) (Fujikawa and McMullen 1983; McMullen and Fujikawa 1985). Identification of the catalytic activity or activities responsible for this cleavage has not been straightforward. Studies in vitro have demonstrated the autoactivation of factor XII as well as activation by kallikrein. Both reactions require the presence of negatively charged surfaces and are accelerated in the presence of kininogen (high molecular weight kininogen, HK) (Griffin and Cochrane 1976; Meier et al. 1977; Silverberg et al. 1980). Recent work suggests that factor XII activation in vivo may occur primarily on endothelial cell surfaces and that, as in vitro, association with kininogen may accelerate the reaction (Mahdi et al. 2002; Schmaier 2004), although alternative pathways and alternative mechanisms for associating factor XII with the cell surface have not been excluded (Joseph et al. 2001). ca9 cef b18 f54 fb9 fec dab c7a Cleavage of a single peptide bond converts factor XII to activated factor XII (factor XIIa) (Fujikawa and McMullen 1983; McMullen and Fujikawa 1985). Identification of the catalytic activity or activities responsible for this cleavage has not been straightforward. Studies in vitro have demonstrated the autoactivation of factor XII as well as activation by kallikrein. Both reactions require the presence of negatively charged surfaces and are accelerated in the presence of kininogen (high molecular weight kininogen, HK) (Griffin and Cochrane 1976; Meier et al. 1977; Silverberg et al. 1980). Recent work suggests that factor XII activation in vivo may occur primarily on endothelial cell surfaces and that, as in vitro, association with kininogen may accelerate the reaction (Mahdi et al. 2002; Schmaier 2004), although alternative pathways and alternative mechanisms for associating factor XII with the cell surface have not been excluded (Joseph et al. 2001). Cleavage of a single peptide bond converts factor XII to activated factor XII (factor XIIa) (Fujikawa and McMullen 1983; McMullen and Fujikawa 1985). Identification of the catalytic activity or activities responsible for this cleavage has not been straightforward. Studies in vitro have demonstrated the autoactivation of factor XII as well as activation by kallikrein. Both reactions require the presence of negatively charged surfaces and are accelerated in the presence of kininogen (high molecular weight kininogen, HK) (Griffin and Cochrane 1976; Meier et al. 1977; Silverberg et al. 1980). Recent work suggests that factor XII activation in vivo may occur primarily on endothelial cell surfaces and that, as in vitro, association with kininogen may accelerate the reaction (Mahdi et al. 2002; Schmaier 2004), although alternative pathways and alternative mechanisms for associating factor XII with the cell surface have not been excluded (Joseph et al. 2001). ca9 cef b18 f54 fb9 fec dab c7a Plasma factor XI binds to the platelet glycoprotein Ib:IX:V complex (Baglia et al. 2002; Greengard et al. 1986). In the body, this reaction occurs specifically on the surfaces of activated platelets, but not on endothelial cells (Baird and Walsh 2002). The stoichiometry of the platelet glycoprotein Ib:IX:V complex has not been established directly, but is inferred from the relative abundances of its components in platelet membranes (Modderman et al. 1992; Shrimpton et al. 2002). Plasma factor XI binds to the platelet glycoprotein Ib:IX:V complex (Baglia et al. 2002; Greengard et al. 1986). In the body, this reaction occurs specifically on the surfaces of activated platelets, but not on endothelial cells (Baird and Walsh 2002). The stoichiometry of the platelet glycoprotein Ib:IX:V complex has not been established directly, but is inferred from the relative abundances of its components in platelet membranes (Modderman et al. 1992; Shrimpton et al. 2002). cee d24 d64 c89 Plasma factor XI binds to the platelet glycoprotein Ib:IX:V complex (Baglia et al. 2002; Greengard et al. 1986). In the body, this reaction occurs specifically on the surfaces of activated platelets, but not on endothelial cells (Baird and Walsh 2002). The stoichiometry of the platelet glycoprotein Ib:IX:V complex has not been established directly, but is inferred from the relative abundances of its components in platelet membranes (Modderman et al. 1992; Shrimpton et al. 2002). Plasma factor XI binds to the platelet glycoprotein Ib:IX:V complex (Baglia et al. 2002; Greengard et al. 1986). In the body, this reaction occurs specifically on the surfaces of activated platelets, but not on endothelial cells (Baird and Walsh 2002). The stoichiometry of the platelet glycoprotein Ib:IX:V complex has not been established directly, but is inferred from the relative abundances of its components in platelet membranes (Modderman et al. 1992; Shrimpton et al. 2002). cee d24 d64 c89 Plasma factor XI binds to the platelet glycoprotein Ib:IX:V complex (Baglia et al. 2002; Greengard et al. 1986). In the body, this reaction occurs specifically on the surfaces of activated platelets, but not on endothelial cells (Baird and Walsh 2002). The stoichiometry of the platelet glycoprotein Ib:IX:V complex has not been established directly, but is inferred from the relative abundances of its components in platelet membranes (Modderman et al. 1992; Shrimpton et al. 2002). Plasma factor XI binds to the platelet glycoprotein Ib:IX:V complex (Baglia et al. 2002; Greengard et al. 1986). In the body, this reaction occurs specifically on the surfaces of activated platelets, but not on endothelial cells (Baird and Walsh 2002). The stoichiometry of the platelet glycoprotein Ib:IX:V complex has not been established directly, but is inferred from the relative abundances of its components in platelet membranes (Modderman et al. 1992; Shrimpton et al. 2002). cee d24 d64 c89 Factor XI, bound to the cell surface, is converted to activated factor XI (factor XIa). Chemically, this reaction involves the cleavage of a single peptide bond in each subunit of the factor XI homodimer; intra- and inter-chain disulfide bonds hold the resulting four polypeptides together (Bouma and Griffin 1977; Kurachi and Davie 1977; McMullen et al. 1991). In the body, this reaction occurs on the surfaces of activated platelets (Greengard et al. 1986; Baglia et al. 2002; Baird and Walsh 2002); when this reaction occurs as a step in the intrinsic ("contact") pathway of blood coagulation, it is catalyzed by activated factor XIIa (Kurachi and Davie 1977, Baglia and Walsh 2000) which in turn is generated through the interactions of factor XII, kallikrein, and kininogen on endothelial cell surfaces (Schmaier 2004). Factor XI, bound to the cell surface, is converted to activated factor XI (factor XIa). Chemically, this reaction involves the cleavage of a single peptide bond in each subunit of the factor XI homodimer; intra- and inter-chain disulfide bonds hold the resulting four polypeptides together (Bouma and Griffin 1977; Kurachi and Davie 1977; McMullen et al. 1991). In the body, this reaction occurs on the surfaces of activated platelets (Greengard et al. 1986; Baglia et al. 2002; Baird and Walsh 2002); when this reaction occurs as a step in the intrinsic ("contact") pathway of blood coagulation, it is catalyzed by activated factor XIIa (Kurachi and Davie 1977, Baglia and Walsh 2000) which in turn is generated through the interactions of factor XII, kallikrein, and kininogen on endothelial cell surfaces (Schmaier 2004). b7a bee d85 b17 Factor XI, bound to the cell surface, is converted to activated factor XI (factor XIa). Chemically, this reaction involves the cleavage of a single peptide bond in each subunit of the factor XI homodimer; intra- and inter-chain disulfide bonds hold the resulting four polypeptides together (Bouma and Griffin 1977; Kurachi and Davie 1977; McMullen et al. 1991). In the body, this reaction occurs on the surfaces of activated platelets (Greengard et al. 1986; Baglia et al. 2002; Baird and Walsh 2002); when this reaction occurs as a step in the intrinsic ("contact") pathway of blood coagulation, it is catalyzed by activated factor XIIa (Kurachi and Davie 1977, Baglia and Walsh 2000) which in turn is generated through the interactions of factor XII, kallikrein, and kininogen on endothelial cell surfaces (Schmaier 2004). Factor XI, bound to the cell surface, is converted to activated factor XI (factor XIa). Chemically, this reaction involves the cleavage of a single peptide bond in each subunit of the factor XI homodimer; intra- and inter-chain disulfide bonds hold the resulting four polypeptides together (Bouma and Griffin 1977; Kurachi and Davie 1977; McMullen et al. 1991). In the body, this reaction occurs on the surfaces of activated platelets (Greengard et al. 1986; Baglia et al. 2002; Baird and Walsh 2002); when this reaction occurs as a step in the intrinsic ("contact") pathway of blood coagulation, it is catalyzed by activated factor XIIa (Kurachi and Davie 1977, Baglia and Walsh 2000) which in turn is generated through the interactions of factor XII, kallikrein, and kininogen on endothelial cell surfaces (Schmaier 2004). b7a bee d85 b17 Factor XI, bound to the cell surface, is converted to activated factor XI (factor XIa). In the body, this reaction occurs on the surfaces of activated platelets (Baglia et al. 2002). Small quantities of factor XI can be activated in a reaction catalyzed by factor XIIa, to initiate formation of a fibrin clot. However, the efficient activation of larger quantities of factor XI, needed to propagate the blood clotting process, appears to be mediated by thrombin (Baglia and Walsh 2000; Gailani and Broze 1993; Naito and Fujikawa 1991; Oliver et al. 1999; Monroe et al. 2002). Factor XI, bound to the cell surface, is converted to activated factor XI (factor XIa). In the body, this reaction occurs on the surfaces of activated platelets (Baglia et al. 2002). Small quantities of factor XI can be activated in a reaction catalyzed by factor XIIa, to initiate formation of a fibrin clot. However, the efficient activation of larger quantities of factor XI, needed to propagate the blood clotting process, appears to be mediated by thrombin (Baglia and Walsh 2000; Gailani and Broze 1993; Naito and Fujikawa 1991; Oliver et al. 1999; Monroe et al. 2002). b7a c3f f30 d32 Factor XI, bound to the cell surface, is converted to activated factor XI (factor XIa). In the body, this reaction occurs on the surfaces of activated platelets (Baglia et al. 2002). Small quantities of factor XI can be activated in a reaction catalyzed by factor XIIa, to initiate formation of a fibrin clot. However, the efficient activation of larger quantities of factor XI, needed to propagate the blood clotting process, appears to be mediated by thrombin (Baglia and Walsh 2000; Gailani and Broze 1993; Naito and Fujikawa 1991; Oliver et al. 1999; Monroe et al. 2002). Factor XI, bound to the cell surface, is converted to activated factor XI (factor XIa). In the body, this reaction occurs on the surfaces of activated platelets (Baglia et al. 2002). Small quantities of factor XI can be activated in a reaction catalyzed by factor XIIa, to initiate formation of a fibrin clot. However, the efficient activation of larger quantities of factor XI, needed to propagate the blood clotting process, appears to be mediated by thrombin (Baglia and Walsh 2000; Gailani and Broze 1993; Naito and Fujikawa 1991; Oliver et al. 1999; Monroe et al. 2002). b7a c3f f30 d32 Factor XIa, bound to platelet glycoprotein (GP) Ib:IX:V on the platelet cell surface, catalyzes the formation of activated factor IX with high efficiency in a reaction that requires Ca++. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.) Factor XIa, bound to platelet glycoprotein (GP) Ib:IX:V on the platelet cell surface, catalyzes the formation of activated factor IX with high efficiency in a reaction that requires Ca++. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.) e03 d59 Factor XIa, bound to platelet glycoprotein (GP) Ib:IX:V on the platelet cell surface, catalyzes the formation of activated factor IX with high efficiency in a reaction that requires Ca++. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.) Factor XIa, bound to platelet glycoprotein (GP) Ib:IX:V on the platelet cell surface, catalyzes the formation of activated factor IX with high efficiency in a reaction that requires Ca++. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.) e03 d59 Factor XIa, bound to platelet glycoprotein (GP) Ib:IX:V on the platelet cell surface, catalyzes the formation of activated factor IX with high efficiency in a reaction that requires Ca++. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.) Factor XIa, bound to platelet glycoprotein (GP) Ib:IX:V on the platelet cell surface, catalyzes the formation of activated factor IX with high efficiency in a reaction that requires Ca++. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.) e03 d59 Factor XIa, bound to platelet glycoprotein (GP) Ib:IX:V on the platelet cell surface, catalyzes the formation of activated factor IX with high efficiency in a reaction that requires Ca++. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.) Factor XIa, bound to platelet glycoprotein (GP) Ib:IX:V on the platelet cell surface, catalyzes the formation of activated factor IX with high efficiency in a reaction that requires Ca++. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.) e03 d59 Factor XIa, bound to platelet glycoprotein (GP) Ib:IX:V on the platelet cell surface, catalyzes the formation of activated factor IX with high efficiency in a reaction that requires Ca++. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.) Factor XIa, bound to platelet glycoprotein (GP) Ib:IX:V on the platelet cell surface, catalyzes the formation of activated factor IX with high efficiency in a reaction that requires Ca++. The amino terminal part of the heavy chain of factor IX, the factor IX activation peptide, is released. (This peptide has no known function.) e03 d59 Factor VIII binds to von Willebrand factor to form a complex. This complex stabilizes factor VIII, which otherwise has a very short half-life in the blood.<P>Factor VIII (Vehar et al. 1984) is a heterodimer containing a heavy and a light polypeptide chain, generated by the proteolytic cleavage of a single large precursor polypeptide. Several forms of the heavy chain are found in vivo, all functionally the same but differing in the amount of the B domain removed by proteolysis. The single form annotated here is the shortest one (Eaton et al. 1986; Hill-Eubanks et al. 1989).<P>In vitro, von Willebrand factor (Titani et al. 1986) can form complexes with factor VIII with a 1:1 stoichiometry. The complexes that form in vivo, however, involve large multimers of von Willebrand factor and varied, but always low, proportions of factor VIII (Vlot et al. 1995). A stoichiometry of one molecule of factor VIII associated with 50 of von Willebrand factor is typical in vivo, and is used here to annotate the factor VIII:von Willebrand factor complex. Factor VIII binds to von Willebrand factor to form a complex. This complex stabilizes factor VIII, which otherwise has a very short half-life in the blood.<P>Factor VIII (Vehar et al. 1984) is a heterodimer containing a heavy and a light polypeptide chain, generated by the proteolytic cleavage of a single large precursor polypeptide. Several forms of the heavy chain are found in vivo, all functionally the same but differing in the amount of the B domain removed by proteolysis. The single form annotated here is the shortest one (Eaton et al. 1986; Hill-Eubanks et al. 1989).<P>In vitro, von Willebrand factor (Titani et al. 1986) can form complexes with factor VIII with a 1:1 stoichiometry. The complexes that form in vivo, however, involve large multimers of von Willebrand factor and varied, but always low, proportions of factor VIII (Vlot et al. 1995). A stoichiometry of one molecule of factor VIII associated with 50 of von Willebrand factor is typical in vivo, and is used here to annotate the factor VIII:von Willebrand factor complex. b26 a34 aea b4d c95 cf8 Factor VIII binds to von Willebrand factor to form a complex. This complex stabilizes factor VIII, which otherwise has a very short half-life in the blood.<P>Factor VIII (Vehar et al. 1984) is a heterodimer containing a heavy and a light polypeptide chain, generated by the proteolytic cleavage of a single large precursor polypeptide. Several forms of the heavy chain are found in vivo, all functionally the same but differing in the amount of the B domain removed by proteolysis. The single form annotated here is the shortest one (Eaton et al. 1986; Hill-Eubanks et al. 1989).<P>In vitro, von Willebrand factor (Titani et al. 1986) can form complexes with factor VIII with a 1:1 stoichiometry. The complexes that form in vivo, however, involve large multimers of von Willebrand factor and varied, but always low, proportions of factor VIII (Vlot et al. 1995). A stoichiometry of one molecule of factor VIII associated with 50 of von Willebrand factor is typical in vivo, and is used here to annotate the factor VIII:von Willebrand factor complex. Factor VIII binds to von Willebrand factor to form a complex. This complex stabilizes factor VIII, which otherwise has a very short half-life in the blood.<P>Factor VIII (Vehar et al. 1984) is a heterodimer containing a heavy and a light polypeptide chain, generated by the proteolytic cleavage of a single large precursor polypeptide. Several forms of the heavy chain are found in vivo, all functionally the same but differing in the amount of the B domain removed by proteolysis. The single form annotated here is the shortest one (Eaton et al. 1986; Hill-Eubanks et al. 1989).<P>In vitro, von Willebrand factor (Titani et al. 1986) can form complexes with factor VIII with a 1:1 stoichiometry. The complexes that form in vivo, however, involve large multimers of von Willebrand factor and varied, but always low, proportions of factor VIII (Vlot et al. 1995). A stoichiometry of one molecule of factor VIII associated with 50 of von Willebrand factor is typical in vivo, and is used here to annotate the factor VIII:von Willebrand factor complex. b26 a34 aea b4d c95 cf8 Factor VIII binds to von Willebrand factor to form a complex. This complex stabilizes factor VIII, which otherwise has a very short half-life in the blood.<P>Factor VIII (Vehar et al. 1984) is a heterodimer containing a heavy and a light polypeptide chain, generated by the proteolytic cleavage of a single large precursor polypeptide. Several forms of the heavy chain are found in vivo, all functionally the same but differing in the amount of the B domain removed by proteolysis. The single form annotated here is the shortest one (Eaton et al. 1986; Hill-Eubanks et al. 1989).<P>In vitro, von Willebrand factor (Titani et al. 1986) can form complexes with factor VIII with a 1:1 stoichiometry. The complexes that form in vivo, however, involve large multimers of von Willebrand factor and varied, but always low, proportions of factor VIII (Vlot et al. 1995). A stoichiometry of one molecule of factor VIII associated with 50 of von Willebrand factor is typical in vivo, and is used here to annotate the factor VIII:von Willebrand factor complex. Factor VIII binds to von Willebrand factor to form a complex. This complex stabilizes factor VIII, which otherwise has a very short half-life in the blood.<P>Factor VIII (Vehar et al. 1984) is a heterodimer containing a heavy and a light polypeptide chain, generated by the proteolytic cleavage of a single large precursor polypeptide. Several forms of the heavy chain are found in vivo, all functionally the same but differing in the amount of the B domain removed by proteolysis. The single form annotated here is the shortest one (Eaton et al. 1986; Hill-Eubanks et al. 1989).<P>In vitro, von Willebrand factor (Titani et al. 1986) can form complexes with factor VIII with a 1:1 stoichiometry. The complexes that form in vivo, however, involve large multimers of von Willebrand factor and varied, but always low, proportions of factor VIII (Vlot et al. 1995). A stoichiometry of one molecule of factor VIII associated with 50 of von Willebrand factor is typical in vivo, and is used here to annotate the factor VIII:von Willebrand factor complex. b26 a34 aea b4d c95 cf8 Factor VIII complexed to von Willibrand factor in the blood is cleaved into several smaller polypeptides that remain associated. The acidic polypeptide on the aminoterminal side of the A3 domain of the light chain is released, however, and as this polypeptide mediates the association of factor VIII with von Willibrand factor, the activated factor VIII is released. While several proteases are capable of catalyzing these cleavages in vitro, only thrombin is active on factor VIII:von Willibrand factor complexes under physiological conditions (Eaton et al. 1986; Hill-Eubanks et al. 1989; Lollar et al. 1988; Pieters et al. 1989) Factor VIII complexed to von Willibrand factor in the blood is cleaved into several smaller polypeptides that remain associated. The acidic polypeptide on the aminoterminal side of the A3 domain of the light chain is released, however, and as this polypeptide mediates the association of factor VIII with von Willibrand factor, the activated factor VIII is released. While several proteases are capable of catalyzing these cleavages in vitro, only thrombin is active on factor VIII:von Willibrand factor complexes under physiological conditions (Eaton et al. 1986; Hill-Eubanks et al. 1989; Lollar et al. 1988; Pieters et al. 1989) b26 a34 c95 f70 Factor VIII complexed to von Willibrand factor in the blood is cleaved into several smaller polypeptides that remain associated. The acidic polypeptide on the aminoterminal side of the A3 domain of the light chain is released, however, and as this polypeptide mediates the association of factor VIII with von Willibrand factor, the activated factor VIII is released. While several proteases are capable of catalyzing these cleavages in vitro, only thrombin is active on factor VIII:von Willibrand factor complexes under physiological conditions (Eaton et al. 1986; Hill-Eubanks et al. 1989; Lollar et al. 1988; Pieters et al. 1989) Factor VIII complexed to von Willibrand factor in the blood is cleaved into several smaller polypeptides that remain associated. The acidic polypeptide on the aminoterminal side of the A3 domain of the light chain is released, however, and as this polypeptide mediates the association of factor VIII with von Willibrand factor, the activated factor VIII is released. While several proteases are capable of catalyzing these cleavages in vitro, only thrombin is active on factor VIII:von Willibrand factor complexes under physiological conditions (Eaton et al. 1986; Hill-Eubanks et al. 1989; Lollar et al. 1988; Pieters et al. 1989) b26 a34 c95 f70 Factor VIII complexed to von Willibrand factor in the blood is cleaved into several smaller polypeptides that remain associated. The acidic polypeptide on the aminoterminal side of the A3 domain of the light chain is released, however, and as this polypeptide mediates the association of factor VIII with von Willibrand factor, the activated factor VIII is released. While several proteases are capable of catalyzing these cleavages in vitro, only thrombin is active on factor VIII:von Willibrand factor complexes under physiological conditions (Eaton et al. 1986; Hill-Eubanks et al. 1989; Lollar et al. 1988; Pieters et al. 1989) Factor VIII complexed to von Willibrand factor in the blood is cleaved into several smaller polypeptides that remain associated. The acidic polypeptide on the aminoterminal side of the A3 domain of the light chain is released, however, and as this polypeptide mediates the association of factor VIII with von Willibrand factor, the activated factor VIII is released. While several proteases are capable of catalyzing these cleavages in vitro, only thrombin is active on factor VIII:von Willibrand factor complexes under physiological conditions (Eaton et al. 1986; Hill-Eubanks et al. 1989; Lollar et al. 1988; Pieters et al. 1989) b26 a34 c95 f70 Factor VIII complexed to von Willibrand factor in the blood is cleaved into several smaller polypeptides that remain associated. The acidic polypeptide on the aminoterminal side of the A3 domain of the light chain is released, however, and as this polypeptide mediates the association of factor VIII with von Willibrand factor, the activated factor VIII is released. While several proteases are capable of catalyzing these cleavages in vitro, only thrombin is active on factor VIII:von Willibrand factor complexes under physiological conditions (Eaton et al. 1986; Hill-Eubanks et al. 1989; Lollar et al. 1988; Pieters et al. 1989) Factor VIII complexed to von Willibrand factor in the blood is cleaved into several smaller polypeptides that remain associated. The acidic polypeptide on the aminoterminal side of the A3 domain of the light chain is released, however, and as this polypeptide mediates the association of factor VIII with von Willibrand factor, the activated factor VIII is released. While several proteases are capable of catalyzing these cleavages in vitro, only thrombin is active on factor VIII:von Willibrand factor complexes under physiological conditions (Eaton et al. 1986; Hill-Eubanks et al. 1989; Lollar et al. 1988; Pieters et al. 1989) b26 a34 c95 f70 Factor VIII complexed to von Willibrand factor in the blood is cleaved into several smaller polypeptides that remain associated. The acidic polypeptide on the aminoterminal side of the A3 domain of the light chain is released, however, and as this polypeptide mediates the association of factor VIII with von Willibrand factor, the activated factor VIII is released. While several proteases are capable of catalyzing these cleavages in vitro, only thrombin is active on factor VIII:von Willibrand factor complexes under physiological conditions (Eaton et al. 1986; Hill-Eubanks et al. 1989; Lollar et al. 1988; Pieters et al. 1989) Factor VIII complexed to von Willibrand factor in the blood is cleaved into several smaller polypeptides that remain associated. The acidic polypeptide on the aminoterminal side of the A3 domain of the light chain is released, however, and as this polypeptide mediates the association of factor VIII with von Willibrand factor, the activated factor VIII is released. While several proteases are capable of catalyzing these cleavages in vitro, only thrombin is active on factor VIII:von Willibrand factor complexes under physiological conditions (Eaton et al. 1986; Hill-Eubanks et al. 1989; Lollar et al. 1988; Pieters et al. 1989) b26 a34 c95 f70 The activated forms of factors VIII and IX associate on a cell surface to form a complex that very efficiently catalyzes the activation of factor X, the so-called "intrinsic tenase complex". In vitro, negatively charged phospholipids can provide an appropriate surface. In the body, the surface is provided by the plasma membranes of activated platelets (Gilbert and Arena 1996). The activated forms of factors VIII and IX associate on a cell surface to form a complex that very efficiently catalyzes the activation of factor X, the so-called "intrinsic tenase complex". In vitro, negatively charged phospholipids can provide an appropriate surface. In the body, the surface is provided by the plasma membranes of activated platelets (Gilbert and Arena 1996). cc1 The activated forms of factors VIII and IX associate on a cell surface to form a complex that very efficiently catalyzes the activation of factor X, the so-called "intrinsic tenase complex". In vitro, negatively charged phospholipids can provide an appropriate surface. In the body, the surface is provided by the plasma membranes of activated platelets (Gilbert and Arena 1996). The activated forms of factors VIII and IX associate on a cell surface to form a complex that very efficiently catalyzes the activation of factor X, the so-called "intrinsic tenase complex". In vitro, negatively charged phospholipids can provide an appropriate surface. In the body, the surface is provided by the plasma membranes of activated platelets (Gilbert and Arena 1996). cc1 The activated forms of factors VIII and IX associate on a cell surface to form a complex that very efficiently catalyzes the activation of factor X, the so-called "intrinsic tenase complex". In vitro, negatively charged phospholipids can provide an appropriate surface. In the body, the surface is provided by the plasma membranes of activated platelets (Gilbert and Arena 1996). The activated forms of factors VIII and IX associate on a cell surface to form a complex that very efficiently catalyzes the activation of factor X, the so-called "intrinsic tenase complex". In vitro, negatively charged phospholipids can provide an appropriate surface. In the body, the surface is provided by the plasma membranes of activated platelets (Gilbert and Arena 1996). cc1 The activated forms of factors VIII and IX associate on a cell surface to form a complex that very efficiently catalyzes the activation of factor X, the so-called "intrinsic tenase complex". In vitro, negatively charged phospholipids can provide an appropriate surface. In the body, the surface is provided by the plasma membranes of activated platelets (Gilbert and Arena 1996). The activated forms of factors VIII and IX associate on a cell surface to form a complex that very efficiently catalyzes the activation of factor X, the so-called "intrinsic tenase complex". In vitro, negatively charged phospholipids can provide an appropriate surface. In the body, the surface is provided by the plasma membranes of activated platelets (Gilbert and Arena 1996). cc1 Factor IXa, in a complex with factor VIIIa on the surfaces of activated platelets (the "intrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) Factor IXa, in a complex with factor VIIIa on the surfaces of activated platelets (the "intrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) beb Factor IXa, in a complex with factor VIIIa on the surfaces of activated platelets (the "intrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) Factor IXa, in a complex with factor VIIIa on the surfaces of activated platelets (the "intrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) beb Factor IXa, in a complex with factor VIIIa on the surfaces of activated platelets (the "intrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) Factor IXa, in a complex with factor VIIIa on the surfaces of activated platelets (the "intrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) beb Factor IXa, in a complex with factor VIIIa on the surfaces of activated platelets (the "intrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) Factor IXa, in a complex with factor VIIIa on the surfaces of activated platelets (the "intrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) beb Factor IXa, in a complex with factor VIIIa on the surfaces of activated platelets (the "intrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) Factor IXa, in a complex with factor VIIIa on the surfaces of activated platelets (the "intrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) beb Factor IXa, in a complex with factor VIIIa on the surfaces of activated platelets (the "intrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) Factor IXa, in a complex with factor VIIIa on the surfaces of activated platelets (the "intrinsic tenase complex"), catalyzes the formation of activated factor X with high efficiency. The amino terminal part of the heavy chain of factor X, the factor X activation peptide, is released. (This peptide has no known function.) beb Activated kallikrein binds to C1Inh (plasma protease C1 inhibitor) (Bock et al. 1986), forming a stable and enzymatically inactive complex. This reaction appears to be the major means by which kallikrein is inactivated (kallikrein can also be inactivated by binding to alpha2-macroglobulin) (Harpel et al. 1985; Ratnoff et al. 1969). Activated kallikrein binds to C1Inh (plasma protease C1 inhibitor) (Bock et al. 1986), forming a stable and enzymatically inactive complex. This reaction appears to be the major means by which kallikrein is inactivated (kallikrein can also be inactivated by binding to alpha2-macroglobulin) (Harpel et al. 1985; Ratnoff et al. 1969). de8 df4 b0f Activated kallikrein binds to C1Inh (plasma protease C1 inhibitor) (Bock et al. 1986), forming a stable and enzymatically inactive complex. This reaction appears to be the major means by which kallikrein is inactivated (kallikrein can also be inactivated by binding to alpha2-macroglobulin) (Harpel et al. 1985; Ratnoff et al. 1969). Activated kallikrein binds to C1Inh (plasma protease C1 inhibitor) (Bock et al. 1986), forming a stable and enzymatically inactive complex. This reaction appears to be the major means by which kallikrein is inactivated (kallikrein can also be inactivated by binding to alpha2-macroglobulin) (Harpel et al. 1985; Ratnoff et al. 1969). de8 df4 b0f Activated kallikrein binds to C1Inh (plasma protease C1 inhibitor) (Bock et al. 1986), forming a stable and enzymatically inactive complex. This reaction appears to be the major means by which kallikrein is inactivated (kallikrein can also be inactivated by binding to alpha2-macroglobulin) (Harpel et al. 1985; Ratnoff et al. 1969). Activated kallikrein binds to C1Inh (plasma protease C1 inhibitor) (Bock et al. 1986), forming a stable and enzymatically inactive complex. This reaction appears to be the major means by which kallikrein is inactivated (kallikrein can also be inactivated by binding to alpha2-macroglobulin) (Harpel et al. 1985; Ratnoff et al. 1969). de8 df4 b0f Activated kallikrein binds to alpha2-macroglobulin (Sottrup-Jensen et al. 1984), forming a stable and enzymatically inactive complex. Under normal conditions in vivo, this reaction appears to be responsible for the inactivation of about 1/6 of activated kallikrein (with C1Inh responsible for the inactivation of about 5/6) (Harpel et al. 1985). Activated kallikrein binds to alpha2-macroglobulin (Sottrup-Jensen et al. 1984), forming a stable and enzymatically inactive complex. Under normal conditions in vivo, this reaction appears to be responsible for the inactivation of about 1/6 of activated kallikrein (with C1Inh responsible for the inactivation of about 5/6) (Harpel et al. 1985). df4 ec3 Activated kallikrein binds to alpha2-macroglobulin (Sottrup-Jensen et al. 1984), forming a stable and enzymatically inactive complex. Under normal conditions in vivo, this reaction appears to be responsible for the inactivation of about 1/6 of activated kallikrein (with C1Inh responsible for the inactivation of about 5/6) (Harpel et al. 1985). Activated kallikrein binds to alpha2-macroglobulin (Sottrup-Jensen et al. 1984), forming a stable and enzymatically inactive complex. Under normal conditions in vivo, this reaction appears to be responsible for the inactivation of about 1/6 of activated kallikrein (with C1Inh responsible for the inactivation of about 5/6) (Harpel et al. 1985). df4 ec3 Activated kallikrein binds to alpha2-macroglobulin (Sottrup-Jensen et al. 1984), forming a stable and enzymatically inactive complex. Under normal conditions in vivo, this reaction appears to be responsible for the inactivation of about 1/6 of activated kallikrein (with C1Inh responsible for the inactivation of about 5/6) (Harpel et al. 1985). Activated kallikrein binds to alpha2-macroglobulin (Sottrup-Jensen et al. 1984), forming a stable and enzymatically inactive complex. Under normal conditions in vivo, this reaction appears to be responsible for the inactivation of about 1/6 of activated kallikrein (with C1Inh responsible for the inactivation of about 5/6) (Harpel et al. 1985). df4 ec3 Activated factor XII (factor XIIa) binds to C1Inh (C1 inhibitor - Bock et al. 1986) to form a stable, inactive complex (Schneider et al. 1973). While several protease inhibitors can form stable complexes with XIIa in vitro, only C1Inh does so to a significant extent under normal conditions in vivo (Pixley et al. 1985). Activated factor XII (factor XIIa) binds to C1Inh (C1 inhibitor - Bock et al. 1986) to form a stable, inactive complex (Schneider et al. 1973). While several protease inhibitors can form stable complexes with XIIa in vitro, only C1Inh does so to a significant extent under normal conditions in vivo (Pixley et al. 1985). de8 ba6 fb1 Activated factor XII (factor XIIa) binds to C1Inh (C1 inhibitor - Bock et al. 1986) to form a stable, inactive complex (Schneider et al. 1973). While several protease inhibitors can form stable complexes with XIIa in vitro, only C1Inh does so to a significant extent under normal conditions in vivo (Pixley et al. 1985). Activated factor XII (factor XIIa) binds to C1Inh (C1 inhibitor - Bock et al. 1986) to form a stable, inactive complex (Schneider et al. 1973). While several protease inhibitors can form stable complexes with XIIa in vitro, only C1Inh does so to a significant extent under normal conditions in vivo (Pixley et al. 1985). de8 ba6 fb1 Activated factor XII (factor XIIa) binds to C1Inh (C1 inhibitor - Bock et al. 1986) to form a stable, inactive complex (Schneider et al. 1973). While several protease inhibitors can form stable complexes with XIIa in vitro, only C1Inh does so to a significant extent under normal conditions in vivo (Pixley et al. 1985). Activated factor XII (factor XIIa) binds to C1Inh (C1 inhibitor - Bock et al. 1986) to form a stable, inactive complex (Schneider et al. 1973). While several protease inhibitors can form stable complexes with XIIa in vitro, only C1Inh does so to a significant extent under normal conditions in vivo (Pixley et al. 1985). de8 ba6 fb1 Membrane-bound factor Xa catalyzes the activation of small amounts of thrombin. The amino terminal portion of prothrombin is released as an activation peptide, which can be cleaved further by activated thrombin. Neither the full-length activation peptide nor its cleavage products have known functions. Membrane-bound factor Xa catalyzes the activation of small amounts of thrombin. The amino terminal portion of prothrombin is released as an activation peptide, which can be cleaved further by activated thrombin. Neither the full-length activation peptide nor its cleavage products have known functions. ea8 Membrane-bound factor Xa catalyzes the activation of small amounts of thrombin. The amino terminal portion of prothrombin is released as an activation peptide, which can be cleaved further by activated thrombin. Neither the full-length activation peptide nor its cleavage products have known functions. Membrane-bound factor Xa catalyzes the activation of small amounts of thrombin. The amino terminal portion of prothrombin is released as an activation peptide, which can be cleaved further by activated thrombin. Neither the full-length activation peptide nor its cleavage products have known functions. ea8 Membrane-bound factor Xa catalyzes the activation of small amounts of thrombin. The amino terminal portion of prothrombin is released as an activation peptide, which can be cleaved further by activated thrombin. Neither the full-length activation peptide nor its cleavage products have known functions. Membrane-bound factor Xa catalyzes the activation of small amounts of thrombin. The amino terminal portion of prothrombin is released as an activation peptide, which can be cleaved further by activated thrombin. Neither the full-length activation peptide nor its cleavage products have known functions. ea8 Membrane-bound factor Xa catalyzes the activation of small amounts of thrombin. The amino terminal portion of prothrombin is released as an activation peptide, which can be cleaved further by activated thrombin. Neither the full-length activation peptide nor its cleavage products have known functions. Membrane-bound factor Xa catalyzes the activation of small amounts of thrombin. The amino terminal portion of prothrombin is released as an activation peptide, which can be cleaved further by activated thrombin. Neither the full-length activation peptide nor its cleavage products have known functions. ea8 Activated thrombin (factor IIa) catalyzes the conversion of factor V to factor Va (activated factor V). The activation peptide released in this reaction has no known function. Activated thrombin (factor IIa) catalyzes the conversion of factor V to factor Va (activated factor V). The activation peptide released in this reaction has no known function. ea8 Activated thrombin (factor IIa) catalyzes the conversion of factor V to factor Va (activated factor V). The activation peptide released in this reaction has no known function. Activated thrombin (factor IIa) catalyzes the conversion of factor V to factor Va (activated factor V). The activation peptide released in this reaction has no known function. ea8 Activated thrombin (factor IIa) catalyzes the conversion of factor V to factor Va (activated factor V). The activation peptide released in this reaction has no known function. Activated thrombin (factor IIa) catalyzes the conversion of factor V to factor Va (activated factor V). The activation peptide released in this reaction has no known function. ea8 Activated thrombin (factor IIa) catalyzes the conversion of factor V to factor Va (activated factor V). The activation peptide released in this reaction has no known function. Activated thrombin (factor IIa) catalyzes the conversion of factor V to factor Va (activated factor V). The activation peptide released in this reaction has no known function. ea8 Factors Va and Xa associate on a membrane surface to form a complex in which the activity of factor Xa on prothrombin is greatly increased (Mann et al. 1988). The presence of negatively charged phospholipid in the membrane greatly facilitates this process, a feature that may contribute to its localization, as such phospholipids are normally on the cytosolic face of the plasma membrane (Devaux 1992), but could be exposed to the extracellular space following platelet activation or mechanical injury to endothelial cells. Factors Va and Xa associate on a membrane surface to form a complex in which the activity of factor Xa on prothrombin is greatly increased (Mann et al. 1988). The presence of negatively charged phospholipid in the membrane greatly facilitates this process, a feature that may contribute to its localization, as such phospholipids are normally on the cytosolic face of the plasma membrane (Devaux 1992), but could be exposed to the extracellular space following platelet activation or mechanical injury to endothelial cells. e58 Factors Va and Xa associate on a membrane surface to form a complex in which the activity of factor Xa on prothrombin is greatly increased (Mann et al. 1988). The presence of negatively charged phospholipid in the membrane greatly facilitates this process, a feature that may contribute to its localization, as such phospholipids are normally on the cytosolic face of the plasma membrane (Devaux 1992), but could be exposed to the extracellular space following platelet activation or mechanical injury to endothelial cells. Factors Va and Xa associate on a membrane surface to form a complex in which the activity of factor Xa on prothrombin is greatly increased (Mann et al. 1988). The presence of negatively charged phospholipid in the membrane greatly facilitates this process, a feature that may contribute to its localization, as such phospholipids are normally on the cytosolic face of the plasma membrane (Devaux 1992), but could be exposed to the extracellular space following platelet activation or mechanical injury to endothelial cells. e58 Factors Va and Xa associate on a membrane surface to form a complex in which the activity of factor Xa on prothrombin is greatly increased (Mann et al. 1988). The presence of negatively charged phospholipid in the membrane greatly facilitates this process, a feature that may contribute to its localization, as such phospholipids are normally on the cytosolic face of the plasma membrane (Devaux 1992), but could be exposed to the extracellular space following platelet activation or mechanical injury to endothelial cells. Factors Va and Xa associate on a membrane surface to form a complex in which the activity of factor Xa on prothrombin is greatly increased (Mann et al. 1988). The presence of negatively charged phospholipid in the membrane greatly facilitates this process, a feature that may contribute to its localization, as such phospholipids are normally on the cytosolic face of the plasma membrane (Devaux 1992), but could be exposed to the extracellular space following platelet activation or mechanical injury to endothelial cells. e58 The membrane-bound Va:Xa (prothrombinase) complex rapidly activates large amounts of thrombin. The membrane-bound Va:Xa (prothrombinase) complex rapidly activates large amounts of thrombin. e58 ea8 The membrane-bound Va:Xa (prothrombinase) complex rapidly activates large amounts of thrombin. The membrane-bound Va:Xa (prothrombinase) complex rapidly activates large amounts of thrombin. e58 ea8 The membrane-bound Va:Xa (prothrombinase) complex rapidly activates large amounts of thrombin. The membrane-bound Va:Xa (prothrombinase) complex rapidly activates large amounts of thrombin. e58 ea8 The membrane-bound Va:Xa (prothrombinase) complex rapidly activates large amounts of thrombin. The membrane-bound Va:Xa (prothrombinase) complex rapidly activates large amounts of thrombin. e58 ea8 The alpha and beta chains of fibrinogen hexamer are cleaved by thrombin to generate fibrin monomer. The amino terminal regions of the cleaved alpha and beta chains are released (fibrinopeptides A and B respectively). The alpha and beta chains of fibrinogen hexamer are cleaved by thrombin to generate fibrin monomer. The amino terminal regions of the cleaved alpha and beta chains are released (fibrinopeptides A and B respectively). f1e The alpha and beta chains of fibrinogen hexamer are cleaved by thrombin to generate fibrin monomer. The amino terminal regions of the cleaved alpha and beta chains are released (fibrinopeptides A and B respectively). The alpha and beta chains of fibrinogen hexamer are cleaved by thrombin to generate fibrin monomer. The amino terminal regions of the cleaved alpha and beta chains are released (fibrinopeptides A and B respectively). f1e The alpha and beta chains of fibrinogen hexamer are cleaved by thrombin to generate fibrin monomer. The amino terminal regions of the cleaved alpha and beta chains are released (fibrinopeptides A and B respectively). The alpha and beta chains of fibrinogen hexamer are cleaved by thrombin to generate fibrin monomer. The amino terminal regions of the cleaved alpha and beta chains are released (fibrinopeptides A and B respectively). f1e The alpha and beta chains of fibrinogen hexamer are cleaved by thrombin to generate fibrin monomer. The amino terminal regions of the cleaved alpha and beta chains are released (fibrinopeptides A and B respectively). The alpha and beta chains of fibrinogen hexamer are cleaved by thrombin to generate fibrin monomer. The amino terminal regions of the cleaved alpha and beta chains are released (fibrinopeptides A and B respectively). f1e The alpha and beta chains of fibrinogen hexamer are cleaved by thrombin to generate fibrin monomer. The amino terminal regions of the cleaved alpha and beta chains are released (fibrinopeptides A and B respectively). The alpha and beta chains of fibrinogen hexamer are cleaved by thrombin to generate fibrin monomer. The amino terminal regions of the cleaved alpha and beta chains are released (fibrinopeptides A and B respectively). f1e Fibrin monomers rapidly and spontaneously associate into large multimers, binding to one another via sites created by fibrinopeptide release (Laudano and Doolittelle 1980). The process of multimerization, and the range of multimer structures that can form in vivo and in vitro, have been studied in detail (Doolittle 1984). Here, multimer size has arbitrarily been set to three fibrin monomers. Fibrin monomers rapidly and spontaneously associate into large multimers, binding to one another via sites created by fibrinopeptide release (Laudano and Doolittelle 1980). The process of multimerization, and the range of multimer structures that can form in vivo and in vitro, have been studied in detail (Doolittle 1984). Here, multimer size has arbitrarily been set to three fibrin monomers. ae9 Activated thrombin cleaves the A chains of factor XIII tetramers in a reaction stimulated by the presence of fibrin multimers. The amino terminal portions of the A chains are released as activation peptides, which have no known function. The resulting factor XIII tetramer remains catalytically inactive. Activated thrombin cleaves the A chains of factor XIII tetramers in a reaction stimulated by the presence of fibrin multimers. The amino terminal portions of the A chains are released as activation peptides, which have no known function. The resulting factor XIII tetramer remains catalytically inactive. c93 Activated thrombin cleaves the A chains of factor XIII tetramers in a reaction stimulated by the presence of fibrin multimers. The amino terminal portions of the A chains are released as activation peptides, which have no known function. The resulting factor XIII tetramer remains catalytically inactive. Activated thrombin cleaves the A chains of factor XIII tetramers in a reaction stimulated by the presence of fibrin multimers. The amino terminal portions of the A chains are released as activation peptides, which have no known function. The resulting factor XIII tetramer remains catalytically inactive. c93 Activated thrombin cleaves the A chains of factor XIII tetramers in a reaction stimulated by the presence of fibrin multimers. The amino terminal portions of the A chains are released as activation peptides, which have no known function. The resulting factor XIII tetramer remains catalytically inactive. Activated thrombin cleaves the A chains of factor XIII tetramers in a reaction stimulated by the presence of fibrin multimers. The amino terminal portions of the A chains are released as activation peptides, which have no known function. The resulting factor XIII tetramer remains catalytically inactive. c93 Activated thrombin cleaves the A chains of factor XIII tetramers in a reaction stimulated by the presence of fibrin multimers. The amino terminal portions of the A chains are released as activation peptides, which have no known function. The resulting factor XIII tetramer remains catalytically inactive. Activated thrombin cleaves the A chains of factor XIII tetramers in a reaction stimulated by the presence of fibrin multimers. The amino terminal portions of the A chains are released as activation peptides, which have no known function. The resulting factor XIII tetramer remains catalytically inactive. c93 Activated thrombin cleaves the A chains of factor XIII tetramers in a reaction stimulated by the presence of fibrin multimers. The amino terminal portions of the A chains are released as activation peptides, which have no known function. The resulting factor XIII tetramer remains catalytically inactive. Activated thrombin cleaves the A chains of factor XIII tetramers in a reaction stimulated by the presence of fibrin multimers. The amino terminal portions of the A chains are released as activation peptides, which have no known function. The resulting factor XIII tetramer remains catalytically inactive. c93 Once the A chains of the Factor XIII tetramer have been cleaved by thrombin, the complex dissociates and the resulting A chain dimer binds Ca++ (one per peptide monomer) to form activated factor XIII (factor XIIIa). Once the A chains of the Factor XIII tetramer have been cleaved by thrombin, the complex dissociates and the resulting A chain dimer binds Ca++ (one per peptide monomer) to form activated factor XIII (factor XIIIa). c93 Once the A chains of the Factor XIII tetramer have been cleaved by thrombin, the complex dissociates and the resulting A chain dimer binds Ca++ (one per peptide monomer) to form activated factor XIII (factor XIIIa). Once the A chains of the Factor XIII tetramer have been cleaved by thrombin, the complex dissociates and the resulting A chain dimer binds Ca++ (one per peptide monomer) to form activated factor XIII (factor XIIIa). c93 Once the A chains of the Factor XIII tetramer have been cleaved by thrombin, the complex dissociates and the resulting A chain dimer binds Ca++ (one per peptide monomer) to form activated factor XIII (factor XIIIa). Once the A chains of the Factor XIII tetramer have been cleaved by thrombin, the complex dissociates and the resulting A chain dimer binds Ca++ (one per peptide monomer) to form activated factor XIII (factor XIIIa). c93 Once the A chains of the Factor XIII tetramer have been cleaved by thrombin, the complex dissociates and the resulting A chain dimer binds Ca++ (one per peptide monomer) to form activated factor XIII (factor XIIIa). Once the A chains of the Factor XIII tetramer have been cleaved by thrombin, the complex dissociates and the resulting A chain dimer binds Ca++ (one per peptide monomer) to form activated factor XIII (factor XIIIa). c93 Once the A chains of the Factor XIII tetramer have been cleaved by thrombin, the complex dissociates and the resulting A chain dimer binds Ca++ (one per peptide monomer) to form activated factor XIII (factor XIIIa). Once the A chains of the Factor XIII tetramer have been cleaved by thrombin, the complex dissociates and the resulting A chain dimer binds Ca++ (one per peptide monomer) to form activated factor XIII (factor XIIIa). c93 Fibrin multimers are stabilized by the formation of multiple covalent crosslinks between the side chains of specific lysine and glutamine residues in fibrinogen alpha and gamma chains, catalyzed by factor XIIIa. Fibrin multimers are stabilized by the formation of multiple covalent crosslinks between the side chains of specific lysine and glutamine residues in fibrinogen alpha and gamma chains, catalyzed by factor XIIIa. Fibrin multimers are stabilized by the formation of multiple covalent crosslinks between the side chains of specific lysine and glutamine residues in fibrinogen alpha and gamma chains, catalyzed by factor XIIIa. Fibrin multimers are stabilized by the formation of multiple covalent crosslinks between the side chains of specific lysine and glutamine residues in fibrinogen alpha and gamma chains, catalyzed by factor XIIIa. Fibrin multimers are stabilized by the formation of multiple covalent crosslinks between the side chains of specific lysine and glutamine residues in fibrinogen alpha and gamma chains, catalyzed by factor XIIIa. Fibrin multimers are stabilized by the formation of multiple covalent crosslinks between the side chains of specific lysine and glutamine residues in fibrinogen alpha and gamma chains, catalyzed by factor XIIIa. Fibrin multimers are stabilized by the formation of multiple covalent crosslinks between the side chains of specific lysine and glutamine residues in fibrinogen alpha and gamma chains, catalyzed by factor XIIIa. Fibrin multimers are stabilized by the formation of multiple covalent crosslinks between the side chains of specific lysine and glutamine residues in fibrinogen alpha and gamma chains, catalyzed by factor XIIIa. Antithrombin III binds to membrane-associated heparin, e.g., on the surface of a normal endothelial cell. This binding event increases the affinity of antithrombin III for thrombin approximately 1000-fold. Antithrombin III binds to membrane-associated heparin, e.g., on the surface of a normal endothelial cell. This binding event increases the affinity of antithrombin III for thrombin approximately 1000-fold. c2b Antithrombin III binds to membrane-associated heparin, e.g., on the surface of a normal endothelial cell. This binding event increases the affinity of antithrombin III for thrombin approximately 1000-fold. Antithrombin III binds to membrane-associated heparin, e.g., on the surface of a normal endothelial cell. This binding event increases the affinity of antithrombin III for thrombin approximately 1000-fold. c2b Antithrombin III binds to membrane-associated heparin, e.g., on the surface of a normal endothelial cell. This binding event increases the affinity of antithrombin III for thrombin approximately 1000-fold. Antithrombin III binds to membrane-associated heparin, e.g., on the surface of a normal endothelial cell. This binding event increases the affinity of antithrombin III for thrombin approximately 1000-fold. c2b Activated thrombin binds to the antithrombin III:heparin complex on the cell surface. Activated thrombin binds to the antithrombin III:heparin complex on the cell surface. c2b Activated thrombin binds to the antithrombin III:heparin complex on the cell surface. Activated thrombin binds to the antithrombin III:heparin complex on the cell surface. c2b Activated thrombin binds to the antithrombin III:heparin complex on the cell surface. Activated thrombin binds to the antithrombin III:heparin complex on the cell surface. c2b Antithrombin III in the complex is cleaved by thrombin, thereupon undergoing a conformational change that stabilizes the thrombin:antithrombin III complex, trapping and inactivating the thrombin moiety. Antithrombin III in the complex is cleaved by thrombin, thereupon undergoing a conformational change that stabilizes the thrombin:antithrombin III complex, trapping and inactivating the thrombin moiety. c2b Antithrombin III in the complex is cleaved by thrombin, thereupon undergoing a conformational change that stabilizes the thrombin:antithrombin III complex, trapping and inactivating the thrombin moiety. Antithrombin III in the complex is cleaved by thrombin, thereupon undergoing a conformational change that stabilizes the thrombin:antithrombin III complex, trapping and inactivating the thrombin moiety. c2b The same conformational change that traps thrombin in its complex with cleaved antithrombin III also decreases the affinity of the latter for heparin, and the complex of cleaved antithrombin III and thrombin dissociates from the cell-bound heparin molecule. The same conformational change that traps thrombin in its complex with cleaved antithrombin III also decreases the affinity of the latter for heparin, and the complex of cleaved antithrombin III and thrombin dissociates from the cell-bound heparin molecule. c2b The same conformational change that traps thrombin in its complex with cleaved antithrombin III also decreases the affinity of the latter for heparin, and the complex of cleaved antithrombin III and thrombin dissociates from the cell-bound heparin molecule. The same conformational change that traps thrombin in its complex with cleaved antithrombin III also decreases the affinity of the latter for heparin, and the complex of cleaved antithrombin III and thrombin dissociates from the cell-bound heparin molecule. c2b The same conformational change that traps thrombin in its complex with cleaved antithrombin III also decreases the affinity of the latter for heparin, and the complex of cleaved antithrombin III and thrombin dissociates from the cell-bound heparin molecule. The same conformational change that traps thrombin in its complex with cleaved antithrombin III also decreases the affinity of the latter for heparin, and the complex of cleaved antithrombin III and thrombin dissociates from the cell-bound heparin molecule. c2b Activated thrombin (factor IIa) binds to thrombomodulin at the external face of the plasma membrane, forming a thrombin:thrombomodulin complex. In this complexed form, the activity of thrombin towards protein C is greatly increased, and as thrombomodulin is particularly abundant on the surfaces of endothelial cells, this association plays a major role in restricting clot formation. Activated thrombin (factor IIa) binds to thrombomodulin at the external face of the plasma membrane, forming a thrombin:thrombomodulin complex. In this complexed form, the activity of thrombin towards protein C is greatly increased, and as thrombomodulin is particularly abundant on the surfaces of endothelial cells, this association plays a major role in restricting clot formation. da7 Activated thrombin (factor IIa) binds to thrombomodulin at the external face of the plasma membrane, forming a thrombin:thrombomodulin complex. In this complexed form, the activity of thrombin towards protein C is greatly increased, and as thrombomodulin is particularly abundant on the surfaces of endothelial cells, this association plays a major role in restricting clot formation. Activated thrombin (factor IIa) binds to thrombomodulin at the external face of the plasma membrane, forming a thrombin:thrombomodulin complex. In this complexed form, the activity of thrombin towards protein C is greatly increased, and as thrombomodulin is particularly abundant on the surfaces of endothelial cells, this association plays a major role in restricting clot formation. da7 Activated thrombin (factor IIa) binds to thrombomodulin at the external face of the plasma membrane, forming a thrombin:thrombomodulin complex. In this complexed form, the activity of thrombin towards protein C is greatly increased, and as thrombomodulin is particularly abundant on the surfaces of endothelial cells, this association plays a major role in restricting clot formation. Activated thrombin (factor IIa) binds to thrombomodulin at the external face of the plasma membrane, forming a thrombin:thrombomodulin complex. In this complexed form, the activity of thrombin towards protein C is greatly increased, and as thrombomodulin is particularly abundant on the surfaces of endothelial cells, this association plays a major role in restricting clot formation. da7 Thrombin complexed with thrombomodulin at the endothelial cell surface cleaves the heavy chain of protein C, generating activated protein C and an activation peptide. The activation peptide has no known function. Thrombin complexed with thrombomodulin at the endothelial cell surface cleaves the heavy chain of protein C, generating activated protein C and an activation peptide. The activation peptide has no known function. da7 f3b Thrombin complexed with thrombomodulin at the endothelial cell surface cleaves the heavy chain of protein C, generating activated protein C and an activation peptide. The activation peptide has no known function. Thrombin complexed with thrombomodulin at the endothelial cell surface cleaves the heavy chain of protein C, generating activated protein C and an activation peptide. The activation peptide has no known function. da7 f3b Thrombin complexed with thrombomodulin at the endothelial cell surface cleaves the heavy chain of protein C, generating activated protein C and an activation peptide. The activation peptide has no known function. Thrombin complexed with thrombomodulin at the endothelial cell surface cleaves the heavy chain of protein C, generating activated protein C and an activation peptide. The activation peptide has no known function. da7 f3b Thrombin complexed with thrombomodulin at the endothelial cell surface cleaves the heavy chain of protein C, generating activated protein C and an activation peptide. The activation peptide has no known function. Thrombin complexed with thrombomodulin at the endothelial cell surface cleaves the heavy chain of protein C, generating activated protein C and an activation peptide. The activation peptide has no known function. da7 f3b Thrombin complexed with thrombomodulin at the endothelial cell surface cleaves the heavy chain of protein C, generating activated protein C and an activation peptide. The activation peptide has no known function. Thrombin complexed with thrombomodulin at the endothelial cell surface cleaves the heavy chain of protein C, generating activated protein C and an activation peptide. The activation peptide has no known function. da7 f3b Activated protein C cleaves peptide bonds in activated factor V (factor Va), converting it to an inactive form (factor Vi). The exact site(s) of cleavage are unknown. Protein S, on the endothelial cell surface, positively regulates this reaction. Although the mechanism of this regulation is unclear, the regulation is physiologically important, as people with reduced amounts of protein S, like people with reduced amounts of protein C, are susceptible to thromboembolism. Activated protein C cleaves peptide bonds in activated factor V (factor Va), converting it to an inactive form (factor Vi). The exact site(s) of cleavage are unknown. Protein S, on the endothelial cell surface, positively regulates this reaction. Although the mechanism of this regulation is unclear, the regulation is physiologically important, as people with reduced amounts of protein S, like people with reduced amounts of protein C, are susceptible to thromboembolism. da7 Activated protein C cleaves peptide bonds in activated factor V (factor Va), converting it to an inactive form (factor Vi). The exact site(s) of cleavage are unknown. Protein S, on the endothelial cell surface, positively regulates this reaction. Although the mechanism of this regulation is unclear, the regulation is physiologically important, as people with reduced amounts of protein S, like people with reduced amounts of protein C, are susceptible to thromboembolism. Activated protein C cleaves peptide bonds in activated factor V (factor Va), converting it to an inactive form (factor Vi). The exact site(s) of cleavage are unknown. Protein S, on the endothelial cell surface, positively regulates this reaction. Although the mechanism of this regulation is unclear, the regulation is physiologically important, as people with reduced amounts of protein S, like people with reduced amounts of protein C, are susceptible to thromboembolism. da7 Activated protein C cleaves peptide bonds in activated factor V (factor Va), converting it to an inactive form (factor Vi). The exact site(s) of cleavage are unknown. Protein S, on the endothelial cell surface, positively regulates this reaction. Although the mechanism of this regulation is unclear, the regulation is physiologically important, as people with reduced amounts of protein S, like people with reduced amounts of protein C, are susceptible to thromboembolism. Activated protein C cleaves peptide bonds in activated factor V (factor Va), converting it to an inactive form (factor Vi). The exact site(s) of cleavage are unknown. Protein S, on the endothelial cell surface, positively regulates this reaction. Although the mechanism of this regulation is unclear, the regulation is physiologically important, as people with reduced amounts of protein S, like people with reduced amounts of protein C, are susceptible to thromboembolism. da7 REACT_4908 REACT_3749 REACT_5349 REACT_2419 REACT_4532 REACT_3035 REACT_3075 REACT_2685 REACT_4532 REACT_3035 REACT_3099 REACT_2937 REACT_4804 REACT_2937 REACT_3461 REACT_4804 REACT_2937 REACT_4714 REACT_5025 REACT_4804 REACT_2937 REACT_5699 REACT_3121 REACT_5305 REACT_2937 REACT_4124 REACT_4236 REACT_4915 REACT_5726 REACT_5214 REACT_3007 REACT_4769 REACT_4765 REACT_2333 REACT_3007 REACT_4769 REACT_3298 REACT_4493 REACT_5706 REACT_3248 REACT_4493 REACT_4190 REACT_3217 REACT_4317 REACT_2936 REACT_5874 REACT_4124 REACT_3449 REACT_4115 REACT_4124 REACT_3449 REACT_2283 REACT_4236 REACT_3099 REACT_2497 REACT_5441 REACT_3099 REACT_4837 REACT_4095 REACT_5594 REACT_4444 REACT_5594 REACT_4285 REACT_2648 REACT_4387 REACT_2653 REACT_2423 REACT_5334 REACT_2621 REACT_5334 REACT_5877 REACT_4175 REACT_3298 REACT_3619 REACT_5904 REACT_5334 REACT_4912 REACT_2599 REACT_4020 REACT_5044 REACT_3007 REACT_4769 3486420 PubMed Characterization of a cDNA coding for human factor VII. 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