Reactome | crosslinked fibrin multimer:tissue plasminogen activator (one-chain):plasminogen -> crosslinked fibrin multimer:tissue plasminogen activator (one-chain) + plasmin

crosslinked fibrin multimer:tissue plasminogen activator (one-chain):plasminogen -> crosslinked fibrin multimer:tissue plasminogen activator (one-chain) + plasmin

Stable Identifier

R-HSA-158750

Type

Reaction [transition]

Species

Homo sapiens

Compartment

extracellular region

ReviewStatus

5/5

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crosslinked fibrin multimer:tissue plasminogen activator (one-chain):plasminogen -> crosslinked fibrin multimer:tissue plasminogen activator (one-chain) + plasmin

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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).

Literature References

PubMed ID	Title	Journal	Year
23193360	The annexin A2/S100A10 system in health and disease: emerging paradigms Falcone, DJ, Tsirka, SE, Kraemer, R, Hedhli, N, Santambrogio, L, Cesarman-Maus, G, Zhai, H, Huang, B, Hajjar, KA	J. Biomed. Biotechnol.	2012
9886297	The crystal structure of a complex of p11 with the annexin II N-terminal peptide Tabaries, S, Renouard, M, Réty, S, Gerke, V, Sopkova, J, Russo-Marie, F, Lewit-Bentley, A, Osterloh, D	Nat. Struct. Biol.	1999
23483454	Annexin A2 system in human biology: cell surface and beyond Luo, M, Hajjar, KA	Semin. Thromb. Hemost.	2013
2496749	The single-chain form of tissue-type plasminogen activator has catalytic activity: studies with a mutant enzyme that lacks the cleavage site Boose, JA, Sambrook, J, Gething, MJ, Gerard, R, Kuismanen, E	Biochemistry	1989
7199524	Kinetics of the activation of plasminogen by human tissue plasminogen activator. Role of fibrin. Hoylaerts, M, Rijken, DC, Lijnen, HR	J Biol Chem	1982