Dissolution of Fibrin Clot (Homo sapiens)

From WikiPathways

Description

Quality Tags

Ontology Terms

Saving...

Bibliography

1. Shigekiyo T, Yoshida H, Matsumoto K, Azuma H, Wakabayashi S, Saito S, Fujikawa K, Koide T.; ''HRG Tokushima: molecular and cellular characterization of histidine-rich glycoprotein (HRG) deficiency.''; PubMed Europe PMC Scholia
2. Moroi M, Aoki N.; ''Isolation and characterization of alpha2-plasmin inhibitor from human plasma. A novel proteinase inhibitor which inhibits activator-induced clot lysis.''; PubMed Europe PMC Scholia
3. Pohl G, Källström M, Bergsdorf N, Wallén P, Jörnvall H.; ''Tissue plasminogen activator: peptide analyses confirm an indirectly derived amino acid sequence, identify the active site serine residue, establish glycosylation sites, and localize variant differences.''; PubMed Europe PMC Scholia
4. Lijnen HR.; ''Elements of the fibrinolytic system.''; PubMed Europe PMC Scholia
5. Luo M, Hajjar KA.; ''Annexin A2 system in human biology: cell surface and beyond.''; PubMed Europe PMC Scholia
6. Ploug M, Rønne E, Behrendt N, Jensen AL, Blasi F, Danø K.; ''Cellular receptor for urokinase plasminogen activator. Carboxyl-terminal processing and membrane anchoring by glycosyl-phosphatidylinositol.''; PubMed Europe PMC Scholia
7. Réty S, Sopkova J, Renouard M, Osterloh D, Gerke V, Tabaries S, Russo-Marie F, Lewit-Bentley A.; ''The crystal structure of a complex of p11 with the annexin II N-terminal peptide.''; PubMed Europe PMC Scholia
8. Ellis V, Scully MF, Kakkar VV.; ''Plasminogen activation initiated by single-chain urokinase-type plasminogen activator. Potentiation by U937 monocytes.''; PubMed Europe PMC Scholia
9. Cubellis MV, Nolli ML, Cassani G, Blasi F.; ''Binding of single-chain prourokinase to the urokinase receptor of human U937 cells.''; PubMed Europe PMC Scholia
10. Behrendt N, Rønne E, Ploug M, Petri T, Løber D, Nielsen LS, Schleuning WD, Blasi F, Appella E, Danø K.; ''The human receptor for urokinase plasminogen activator. NH2-terminal amino acid sequence and glycosylation variants.''; PubMed Europe PMC Scholia
11. Koide T, Foster D, Yoshitake S, Davie EW.; ''Amino acid sequence of human histidine-rich glycoprotein derived from the nucleotide sequence of its cDNA.''; PubMed Europe PMC Scholia
12. Cubellis MV, Andreasen P, Ragno P, Mayer M, Danø K, Blasi F.; ''Accessibility of receptor-bound urokinase to type-1 plasminogen activator inhibitor.''; PubMed Europe PMC Scholia
13. Hedhli N, Falcone DJ, Huang B, Cesarman-Maus G, Kraemer R, Zhai H, Tsirka SE, Santambrogio L, Hajjar KA.; ''The annexin A2/S100A10 system in health and disease: emerging paradigms.''; PubMed Europe PMC Scholia
14. Lijnen HR, Zamarron C, Blaber M, Winkler ME, Collen D.; ''Activation of plasminogen by pro-urokinase. I. Mechanism.''; PubMed Europe PMC Scholia
15. Kohler HP, Grant PJ.; ''Plasminogen-activator inhibitor type 1 and coronary artery disease.''; PubMed Europe PMC Scholia
16. Kruithof EK, Vassalli JD, Schleuning WD, Mattaliano RJ, Bachmann F.; ''Purification and characterization of a plasminogen activator inhibitor from the histiocytic lymphoma cell line U-937.''; PubMed Europe PMC Scholia
17. Petersen TE, Martzen MR, Ichinose A, Davie EW.; ''Characterization of the gene for human plasminogen, a key proenzyme in the fibrinolytic system.''; PubMed Europe PMC Scholia
18. Higgins DL, Vehar GA.; ''Interaction of one-chain and two-chain tissue plasminogen activator with intact and plasmin-degraded fibrin.''; PubMed Europe PMC Scholia
19. Lijnen HR, Hoylaerts M, Collen D.; ''Isolation and characterization of a human plasma protein with affinity for the lysine binding sites in plasminogen. Role in the regulation of fibrinolysis and identification as histidine-rich glycoprotein.''; PubMed Europe PMC Scholia
20. Lijnen HR, Holmes WE, van Hoef B, Wiman B, Rodriguez H, Collen D.; ''Amino-acid sequence of human alpha 2-antiplasmin.''; PubMed Europe PMC Scholia
21. Hoylaerts M, Rijken DC, Lijnen HR, Collen D.; ''Kinetics of the activation of plasminogen by human tissue plasminogen activator. Role of fibrin.''; PubMed Europe PMC Scholia
22. Estreicher A, Mühlhauser J, Carpentier JL, Orci L, Vassalli JD.; ''The receptor for urokinase type plasminogen activator polarizes expression of the protease to the leading edge of migrating monocytes and promotes degradation of enzyme inhibitor complexes.''; PubMed Europe PMC Scholia
23. Ellis V, Behrendt N, Danø K.; ''Plasminogen activation by receptor-bound urokinase. A kinetic study with both cell-associated and isolated receptor.''; PubMed Europe PMC Scholia
24. Wagner OF, de Vries C, Hohmann C, Veerman H, Pannekoek H.; ''Interaction between plasminogen activator inhibitor type 1 (PAI-1) bound to fibrin and either tissue-type plasminogen activator (t-PA) or urokinase-type plasminogen activator (u-PA). Binding of t-PA/PAI-1 complexes to fibrin mediated by both the finger and the kringle-2 domain of t-PA.''; PubMed Europe PMC Scholia
25. Chapman HA.; ''Plasminogen activators, integrins, and the coordinated regulation of cell adhesion and migration.''; PubMed Europe PMC Scholia
26. Boose JA, Kuismanen E, Gerard R, Sambrook J, Gething MJ.; ''The single-chain form of tissue-type plasminogen activator has catalytic activity: studies with a mutant enzyme that lacks the cleavage site.''; PubMed Europe PMC Scholia

History

External references

DataNodes

Name	Type	Database reference	Comment
ANXA2	Protein	P07355 (Uniprot-TrEMBL)
ANXA2:S100A10 tetramer	Complex	R-HSA-5336141 (Reactome)
HRG	Protein	P04196 (Uniprot-TrEMBL)
HRG	Protein	P04196 (Uniprot-TrEMBL)
N-glycyl-glycosylphosphatidylinositolethanolamine-PLAUR	Protein	Q03405 (Uniprot-TrEMBL)
N-glycyl-glycosylphosphatidylinositolethanolamine-PLAUR	Protein	Q03405 (Uniprot-TrEMBL)
PAI-1:urokinase plasminogen activator (two-chain):uPAR	Complex	R-HSA-159013 (Reactome)
PAI-2:urokinase plasminogen activator (two-chain):uPAR	Complex	R-HSA-159009 (Reactome)
PLAT(311-562)	Protein	P00750 (Uniprot-TrEMBL)
PLAT(36-310)	Protein	P00750 (Uniprot-TrEMBL)
PLAT(36-562)	Protein	P00750 (Uniprot-TrEMBL)
PLAT(36-562)	Protein	P00750 (Uniprot-TrEMBL)
PLAU(179-431)	Protein	P00749 (Uniprot-TrEMBL)
PLAU(21-177)	Protein	P00749 (Uniprot-TrEMBL)
PLAU(21-431)	Protein	P00749 (Uniprot-TrEMBL)
PLAU(21-431)	Protein	P00749 (Uniprot-TrEMBL)
PLG(20-580)	Protein	P00747 (Uniprot-TrEMBL)
PLG(20-810)	Protein	P00747 (Uniprot-TrEMBL)
PLG(20-810)	Protein	P00747 (Uniprot-TrEMBL)
PLG(581-810)	Protein	P00747 (Uniprot-TrEMBL)
Plasmin	Complex	R-HSA-158770 (Reactome)
S100A10	Protein	P60903 (Uniprot-TrEMBL)
SERPINB2	Protein	P05120 (Uniprot-TrEMBL)
SERPINB2	Protein	P05120 (Uniprot-TrEMBL)
SERPINE1	Protein	P05121 (Uniprot-TrEMBL)
SERPINE1-like proteins		R-HSA-4127462 (Reactome)	This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis.
SERPINE1-like proteins		R-HSA-4127463 (Reactome)	This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis.
SERPINE1	Protein	P05121 (Uniprot-TrEMBL)
SERPINF2	Protein	P08697 (Uniprot-TrEMBL)
SERPINF2	Protein	P08697 (Uniprot-TrEMBL)
Zn2+	Metabolite	CHEBI:29105 (ChEBI)
alpha-2-antiplasmin:plasmin	Complex	R-HSA-158878 (Reactome)
fibrin multimer, crosslinked:tissue plasminogen activator (one-chain):plasminogen activator inhibitor 1	Complex	R-HSA-158791 (Reactome)
fibrin multimer, crosslinked:tissue plasminogen activator (one-chain):plasminogen	Complex	R-HSA-158777 (Reactome)
fibrin multimer, crosslinked:tissue plasminogen activator (two-chain):plasminogen activator inhibitor 1	Complex	R-HSA-158789 (Reactome)
fibrin multimer, crosslinked:tissue plasminogen activator (two-chain):plasminogen	Complex	R-HSA-158786 (Reactome)
fibrin digestion products (plasmin)		R-HSA-158774 (Reactome)
fibrin multimer, crosslinked:tissue plasminogen activator (one-chain)	Complex	R-HSA-158764 (Reactome)
fibrin multimer, crosslinked:tissue plasminogen activator (two-chain)	Complex	R-HSA-158745 (Reactome)
fibrin multimer, crosslinked		R-NUL-157771 (Reactome)
histidine-rich glycoprotein:plasminogen	Complex	R-HSA-158703 (Reactome)
plasminogen activator inhibitor		R-HSA-2990857 (Reactome)	This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis.
plasminogen:histidine-rich glycoprotein	Complex	R-HSA-158961 (Reactome)
urokinase plasminogen activator (one-chain):uPAR	Complex	R-HSA-158926 (Reactome)
urokinase plasminogen activator (two-chain):uPAR	Complex	R-HSA-158969 (Reactome)

Annotated Interactions

Source	Target	Type	Database reference	Comment
ANXA2:S100A10 tetramer		Arrow	R-HSA-158750 (Reactome)
	HRG	Arrow	R-HSA-158721 (Reactome)
	HRG	Arrow	R-HSA-158925 (Reactome)
	HRG	Arrow	R-HSA-158982 (Reactome)
HRG			R-HSA-158722 (Reactome)
HRG			R-HSA-158941 (Reactome)
N-glycyl-glycosylphosphatidylinositolethanolamine-PLAUR			R-HSA-158959 (Reactome)
	PAI-1:urokinase plasminogen activator (two-chain):uPAR	Arrow	R-HSA-159005 (Reactome)
	PAI-2:urokinase plasminogen activator (two-chain):uPAR	Arrow	R-HSA-159001 (Reactome)
PLAT(36-562)			R-HSA-158781 (Reactome)
PLAU(21-431)			R-HSA-158959 (Reactome)
	PLG(20-810)	Arrow	R-HSA-158721 (Reactome)
PLG(20-810)			R-HSA-158722 (Reactome)
PLG(20-810)			R-HSA-158756 (Reactome)
PLG(20-810)			R-HSA-158784 (Reactome)
PLG(20-810)			R-HSA-158941 (Reactome)
	Plasmin	Arrow	R-HSA-158744 (Reactome)
	Plasmin	Arrow	R-HSA-158750 (Reactome)
	Plasmin	Arrow	R-HSA-158925 (Reactome)
	Plasmin	Arrow	R-HSA-158982 (Reactome)
Plasmin			R-HSA-158893 (Reactome)
Plasmin		mim-catalysis	R-HSA-158747 (Reactome)
Plasmin		mim-catalysis	R-HSA-158766 (Reactome)
Plasmin		mim-catalysis	R-HSA-158942 (Reactome)
			R-HSA-158721 (Reactome)	Plasminogen reversibly binds histidine-rich glycoprotein (HRG). The resulting complex interacts poorly with fibrin, suggesting that HRG might have an anti-fibrinolytic (clot-stabilizing) effect in vivo (Lijnen et al. 1980). Consistent with this suggestion, individuals with chronically reduced plasma HRG concentrations are susceptible to thrombosis (Shigekiyo et al. 1998).
			R-HSA-158722 (Reactome)	Plasminogen reversibly binds histidine-rich glycoprotein (HRG). The resulting complex interacts poorly with fibrin, suggesting that HRG might have an anti-fibrinolytic (clot-stabilizing) effect in vivo (Lijnen et al. 1980). Consistent with this suggestion, individuals with chronically reduced plasma HRG concentrations are susceptible to thrombosis (Shigekiyo et al. 1998).
			R-HSA-158744 (Reactome)	At the beginning of this reaction, 1 molecule of 'fibrin multimer, crosslinked:tissue plasminogen activator (two-chain):plasminogen' is present. At the end of this reaction, 1 molecule of 'plasmin', and 1 molecule of 'fibrin multimer, crosslinked:tissue plasminogen activator (two-chain)' are present. This reaction takes place in the 'extracellular region' and is mediated by the 'plasminogen activator activity' of 'fibrin multimer, crosslinked:tissue plasminogen activator (two-chain):plasminogen'.
			R-HSA-158747 (Reactome)	Once plasmin has been activated, in the initial stage of the fibrinolysis process, it can catalyze the conversion of fibrin-bound tissue plasminogen activator (one-chain) to its more active two-chain form, increasing the rate at which additional plasminogen molecules can be activated.
			R-HSA-158750 (Reactome)	Plasminogen bound to fibrin is cleaved and activated by tissue plasminogen activator also bound to the fibrin. The association of both plasminogen and tissue plasminogen activator with a fibrin clot juxtaposes the two molecules, facilitating their interaction (Hoylaerts et al. 1982). Early studies suggested that tissue plasminogen activator itself might require activation (conversion to its two-chain form) before it could catalyze this reaction (e.g., Higgins and Vehar 1987). More recent work (Boose et al. 1989) indicates that the single-chain form of the molecule is catalytically active, although cleavage increases its activity and may thus serve to accelerate the later stages of fibrinolysis. Annexin A2 (ANXA2) is a multicompartmental, multifunctional protein that forms a heterotetramer with its endothelial cell-surface binding partner protein S100-A10 (S100A10) (Rety et al. 1999). The tetramer is able to positively modulate tissue plasminogen activator-dependent activation of the fibrinolytic protease, plasmin from its plasminogen precursor (Luo et al. 2013, Hedhli et al. 2012).
			R-HSA-158756 (Reactome)	At the beginning of this reaction, 1 molecule of 'plasminogen', and 1 molecule of 'fibrin multimer, crosslinked:tissue plasminogen activator (two-chain)' are present. At the end of this reaction, 1 molecule of 'fibrin multimer, crosslinked:tissue plasminogen activator (two-chain):plasminogen' is present. This reaction takes place in the 'extracellular region'.
			R-HSA-158766 (Reactome)	Plasmin, generated at the surfaces of the fibrin clot by tissue plasminogen activator or at the surfaces of cells by urokinase plasminogen activator, catalyzes the hydrolysis of fibrin to soluble fragments (Chapman 1997).
			R-HSA-158781 (Reactome)	The first step in the dissolution of a fibrin clot is the association of the one-chain form of tissue plasminogen activator with fibrin.
			R-HSA-158784 (Reactome)	Plasminogen associates with tissue plasminogen activator bound to fibrin.
			R-HSA-158795 (Reactome)	Plasminogen activator inhibitor 1, a serpin, binds to fibrin-associated tissue plasminogen activator. The resulting stable complex remains associated with fibrin but cannot activate plasminogen (Wagner et al. 1989). The importance of this step in the regulation of clot dissolution in vivo is indicated by the occurence of thrombosis in individuals with abnormally little tissue plasminogen activator or abnormally much plasminogen activator inhibitor (Juhan-Vague et al. 1987).
			R-HSA-158800 (Reactome)	Plasminogen activator inhibitor 1, a serpin, binds to fibrin-associated tissue plasminogen activator. The resulting stable complex remains associated with fibrin but cannot activate plasminogen (Wagner et al. 1989). The importance of this step in the regulation of clot dissolution in vivo is indicated by the occurence of thrombosis in individuals with abnormally little tissue plasminogen activator or abnormally much plasminogen activator inhibitor (Juhan-Vague et al. 1987).
			R-HSA-158893 (Reactome)	Plasmin binds the serpin alpha-2-antiplasmin, forming a stable and catalytically inactive complex. While several serpin proteins bind and inactivate plasmin in vitro, alpha-2-antiplasmin appears to be the only one with substantial plasmin-neutralizing activity in vivo (Moroi and Aoki 1976; Lijnen et al. 1987).
			R-HSA-158925 (Reactome)	Plasminogen, tethered to the cell surface by its association with histidine-rich glycoprotein, is rapidly cleaved and activated to plasmin by the action of urokinase plasminogen activator(two-chain form) bound to uPAR, its cell-surface receptor. The association of both substrate and enzyme with the cell surface is necessary for the reaction to proceed efficiently (Ellis et al. 1989, 1991).
			R-HSA-158941 (Reactome)	Extracellular plasminogen binds with high affinity to histidine-rich glycoprotein on the plasma membrane. Binding requires Zn++ in concentrations higher than those found in normal plasma, but that can be generated, e.g., by platelet activation (Jones et al. 2004).
			R-HSA-158942 (Reactome)	The small amount of plasmin generated by the activity of the one-chain form of urokinase plasminogen activator in turn cleaves urokinase plasminogen activator, converting it to its substantially more active two-chain form (Cubellis et al. 1986; Lijnen et al. 1991).
			R-HSA-158959 (Reactome)	The uncleaved (one-chain) form of urokinase plasminogen activator associates with urokinase plasminogen activator receptor (uPAR), forming a complex at the cell surface (Cubellis et al. 1986). The complex is anchored to the outer face of the plasma membrane by a glycophosphatidylinositol moiety at the carboxy terminus of uPAR (Behrendt et al. 1990; Ploug et al. 1991).
			R-HSA-158982 (Reactome)	Plasminogen, tethered to the cell surface by its association with histidine-rich glycoprotein, is cleaved and activated to plasmin by the action of urokinase plasminogen activator bound to uPAR, its cell-surface receptor. The association of both substrate and enzyme with the cell surface is necessary for the reaction to proceed efficiently (Ellis et al. 1991). While the one-chain form of urokinase plasminogen activator is lower than that of the two-chain form, it is still sufficient to initiate the process of plasmin activation (Ellis et al. 1989; Lijnen et al. 1986).
			R-HSA-159001 (Reactome)	Activated (two-chain) urokinase plasminogen activator binds plasminogen activator inhibitor 2, a serpin, to form a stable, inactive complex that remains associated with uPAR on the plasma membrane (Estreicher et al. 1990; Kruithof et al. 1986).
			R-HSA-159005 (Reactome)	Activated (two-chain) urokinase plasminogen activator binds plasminogen activator inhibitor 1, a serpin, to form a stable, inactive complex that remains associated with uPAR on the plasma membrane (Cubellis et al. 1989).
SERPINB2			R-HSA-159001 (Reactome)
SERPINE1-like proteins		mim-catalysis	R-HSA-158795 (Reactome)
SERPINE1-like proteins		mim-catalysis	R-HSA-158800 (Reactome)
SERPINE1-like proteins		mim-catalysis	R-HSA-159005 (Reactome)
SERPINE1			R-HSA-158795 (Reactome)
SERPINE1			R-HSA-158800 (Reactome)
SERPINE1			R-HSA-159005 (Reactome)
SERPINF2			R-HSA-158893 (Reactome)
SERPINF2		mim-catalysis	R-HSA-158893 (Reactome)
Zn2+		Arrow	R-HSA-158941 (Reactome)
	alpha-2-antiplasmin:plasmin	Arrow	R-HSA-158893 (Reactome)
	fibrin multimer, crosslinked:tissue plasminogen activator (one-chain):plasminogen activator inhibitor 1	Arrow	R-HSA-158795 (Reactome)
	fibrin multimer, crosslinked:tissue plasminogen activator (one-chain):plasminogen	Arrow	R-HSA-158784 (Reactome)
fibrin multimer, crosslinked:tissue plasminogen activator (one-chain):plasminogen			R-HSA-158750 (Reactome)
fibrin multimer, crosslinked:tissue plasminogen activator (one-chain):plasminogen		mim-catalysis	R-HSA-158750 (Reactome)
	fibrin multimer, crosslinked:tissue plasminogen activator (two-chain):plasminogen activator inhibitor 1	Arrow	R-HSA-158800 (Reactome)
	fibrin multimer, crosslinked:tissue plasminogen activator (two-chain):plasminogen	Arrow	R-HSA-158756 (Reactome)
fibrin multimer, crosslinked:tissue plasminogen activator (two-chain):plasminogen			R-HSA-158744 (Reactome)
fibrin multimer, crosslinked:tissue plasminogen activator (two-chain):plasminogen		mim-catalysis	R-HSA-158744 (Reactome)
	fibrin digestion products (plasmin)	Arrow	R-HSA-158766 (Reactome)
	fibrin multimer, crosslinked:tissue plasminogen activator (one-chain)	Arrow	R-HSA-158750 (Reactome)
	fibrin multimer, crosslinked:tissue plasminogen activator (one-chain)	Arrow	R-HSA-158781 (Reactome)
fibrin multimer, crosslinked:tissue plasminogen activator (one-chain)			R-HSA-158747 (Reactome)
fibrin multimer, crosslinked:tissue plasminogen activator (one-chain)			R-HSA-158784 (Reactome)
fibrin multimer, crosslinked:tissue plasminogen activator (one-chain)			R-HSA-158795 (Reactome)
	fibrin multimer, crosslinked:tissue plasminogen activator (two-chain)	Arrow	R-HSA-158744 (Reactome)
	fibrin multimer, crosslinked:tissue plasminogen activator (two-chain)	Arrow	R-HSA-158747 (Reactome)
fibrin multimer, crosslinked:tissue plasminogen activator (two-chain)			R-HSA-158756 (Reactome)
fibrin multimer, crosslinked:tissue plasminogen activator (two-chain)			R-HSA-158800 (Reactome)
fibrin multimer, crosslinked			R-HSA-158766 (Reactome)
fibrin multimer, crosslinked			R-HSA-158781 (Reactome)
	histidine-rich glycoprotein:plasminogen	Arrow	R-HSA-158722 (Reactome)
histidine-rich glycoprotein:plasminogen			R-HSA-158721 (Reactome)
plasminogen activator inhibitor		mim-catalysis	R-HSA-159001 (Reactome)
	plasminogen:histidine-rich glycoprotein	Arrow	R-HSA-158941 (Reactome)
plasminogen:histidine-rich glycoprotein			R-HSA-158925 (Reactome)
plasminogen:histidine-rich glycoprotein			R-HSA-158982 (Reactome)
	urokinase plasminogen activator (one-chain):uPAR	Arrow	R-HSA-158959 (Reactome)
urokinase plasminogen activator (one-chain):uPAR			R-HSA-158942 (Reactome)
urokinase plasminogen activator (one-chain):uPAR		mim-catalysis	R-HSA-158982 (Reactome)
	urokinase plasminogen activator (two-chain):uPAR	Arrow	R-HSA-158942 (Reactome)
urokinase plasminogen activator (two-chain):uPAR			R-HSA-159001 (Reactome)
urokinase plasminogen activator (two-chain):uPAR			R-HSA-159005 (Reactome)
urokinase plasminogen activator (two-chain):uPAR		mim-catalysis	R-HSA-158925 (Reactome)