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

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

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

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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 Hedhli, N, Falcone, DJ, Huang, B, Cesarman-Maus, G, Kraemer, R, Zhai, H, Tsirka, SE, Santambrogio, L, Hajjar, KA	J. Biomed. Biotechnol.	2012
9886297	The crystal structure of a complex of p11 with the annexin II N-terminal peptide Réty, S, Sopkova, J, Renouard, M, Osterloh, D, Gerke, V, Tabaries, S, Russo-Marie, F, Lewit-Bentley, A	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, Kuismanen, E, Gerard, R, Sambrook, J, Gething, MJ	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