Dissolution of Fibrin Clot (Homo sapiens)

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1376, 76, 1610, 114, 5, 121-31315, 161412, 188, 91-34, 5157, 1517-196, 15, 20plasma membraneplasminogenfibrin multimer, crosslinked:tissue plasminogen activator (one-chain):plasminogen activator inhibitor 1PAI-2:urokinase plasminogen activator (two-chain):uPARfibrin multimer, crosslinked:tissue plasminogen activator (two-chain):plasminogenhistidine-rich glycoproteinfibrin multimer, crosslinked:tissue plasminogen activator (two-chain)fibrin multimer, crosslinkedurokinase plasminogen activator (one-chain)plasminogen activator inhibitor 2plasminogen activator inhibitor 2Alpha-2-antiplasminfibrin multimer, crosslinked:tissue plasminogen activator (one-chain):plasminogentissue plasminogen activator (one-chain)urokinase plasminogen activator (one-chain):uPARplasminZn++histidine-rich glycoprotein:plasminogenplasminogen activator inhibitor 1fibrin multimer, crosslinked:tissue plasminogen activator (two-chain):plasminogen activator inhibitor 1plasminogen activator inhibitor 1histidine-rich glycoproteinPAI-1:urokinase plasminogen activator (two-chain):uPARplasminogen:histidine-rich glycoproteinurokinase plasminogen activator receptorfibrin digestion products (plasmin)alpha-2-antiplasmin:plasminurokinase plasminogen activator (two-chain):uPARfibrin multimer, crosslinked:tissue plasminogen activator (one-chain)


Description

The crosslinked fibrin multimers in a clot are broken down to soluble polypeptides by plasmin, a serine protease. Plasmin can be generated from its inactive precursor plasminogen and recruited to the site of a fibrin clot in two ways, by interaction with tissue plasminogen activator at the surface of a fibrin clot, and by interaction with urokinase plasminogen activator at a cell surface. The first mechanism appears to be the major one responsible for the dissolution of clots within blood vessels. The second, although capable of mediating clot dissolution, may normally play a major role in tissue remodeling, cell migration, and inflammation (Chapman 1997; Lijnen 2001). These other functions of urokinase plasminogen activator will be annotated in future versions of Reactome.
Clot dissolution is regulated in two ways. First, efficient plasmin activation and fibrinolysis occur only in complexes formed at the clot surface or on a cell membrane - proteins free in the blood are inefficient catalysts and are rapidly inactivated. Second, both plasminogen activators and plasmin itself are inactivated by specific serpins, proteins that bind to serine proteases to form stable, enzymatically inactive complexes (Kohler and Grant 2000).
These events are outlined in the drawing: black arrows connect the substrates (inputs) and products (outputs) of individual reactions, and blue lines connect output activated enzymes to the other reactions that they catalyze.

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Bibliography

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  4. Lijnen HR.; ''Elements of the fibrinolytic system.''; PubMed Europe PMC Scholia
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  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
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History

View all...
CompareRevisionActionTimeUserComment
114732view16:21, 25 January 2021ReactomeTeamReactome version 75
113176view11:24, 2 November 2020ReactomeTeamReactome version 74
112404view15:34, 9 October 2020ReactomeTeamReactome version 73
101308view11:19, 1 November 2018ReactomeTeamreactome version 66
100845view20:51, 31 October 2018ReactomeTeamreactome version 65
100386view19:25, 31 October 2018ReactomeTeamreactome version 64
99933view16:09, 31 October 2018ReactomeTeamreactome version 63
99488view14:41, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99140view12:40, 31 October 2018ReactomeTeamreactome version 62
93940view13:46, 16 August 2017ReactomeTeamreactome version 61
93529view11:26, 9 August 2017ReactomeTeamreactome version 61
86628view09:22, 11 July 2016ReactomeTeamreactome version 56
83356view10:57, 18 November 2015ReactomeTeamVersion54
81518view13:03, 21 August 2015ReactomeTeamVersion53
76989view08:28, 17 July 2014ReactomeTeamFixed remaining interactions
76694view12:06, 16 July 2014ReactomeTeamFixed remaining interactions
76020view10:08, 11 June 2014ReactomeTeamRe-fixing comment source
75729view11:20, 10 June 2014ReactomeTeamReactome 48 Update
75079view14:02, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74726view08:48, 30 April 2014ReactomeTeamReactome46
68916view17:31, 8 July 2013MaintBotUpdated to 2013 gpml schema
45190view10:02, 7 October 2011MartijnVanIerselOntology Term : 'regulatory pathway' added !
42025view21:51, 4 March 2011MaintBotAutomatic update
39828view05:51, 21 January 2011MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
Alpha-2-

antiplasmin

ProteinP08697 (UniProt)
PAI-1:urokinase

plasminogen activator (two- chain):uPAR

ComplexREACT_4824 (Reactome)
PAI-2:urokinase

plasminogen activator (two- chain):uPAR

ComplexREACT_4630 (Reactome)
Zn++ Metabolite29105 (ChEBI)
alpha-2-

antiplasmin: plasmin

ComplexREACT_5642 (Reactome)
fibrin digestion

products (plasmin)

UnknownREACT_5325 (Reactome)
fibrin multimer,

crosslinked

UnknownREACT_2721 (Reactome)
fibrin multimer,

crosslinked:tissue plasminogen activator (one- chain)

ComplexREACT_4365 (Reactome)
fibrin multimer,

crosslinked:tissue plasminogen activator (two- chain)

ComplexREACT_3996 (Reactome)
fibrin multimer,

crosslinked:tissue plasminogen activator (one-chain): plasminogen

ComplexREACT_3214 (Reactome)
fibrin multimer,

crosslinked:tissue plasminogen activator (one-chain): plasminogen activator inhibitor 1

ComplexREACT_5096 (Reactome)
fibrin multimer,

crosslinked:tissue plasminogen activator (two-chain): plasminogen

ComplexREACT_3415 (Reactome)
fibrin multimer,

crosslinked:tissue plasminogen activator (two-chain): plasminogen activator inhibitor 1

ComplexREACT_4783 (Reactome)
histidine-rich

glycoprotein

ProteinP04196 (UniProt)
histidine-rich

glycoprotein: plasminogen

ComplexREACT_5514 (Reactome)
plasmin ComplexREACT_4641 (Reactome)
plasminogen ProteinP00747 (UniProt)
plasminogen

activator inhibitor 1

ProteinP05121 (UniProt)
plasminogen

activator inhibitor 2

ProteinP05120 (UniProt)
plasminogen:

histidine-rich glycoprotein

ComplexREACT_5880 (Reactome)
tissue plasminogen

activator (one-chain)

ProteinP00750 (UniProt)
urokinase

plasminogen activator (one-chain)

ProteinP00749 (UniProt)
urokinase

plasminogen activator (one-chain): uPAR

ComplexREACT_4234 (Reactome)
urokinase

plasminogen activator (two- chain):uPAR

ComplexREACT_5050 (Reactome)
urokinase

plasminogen activator receptor

ProteinQ03405 (UniProt)

Annotated Interactions

No annotated interactions

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