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
Species
Homo sapiens
Compartment
Summation

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
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
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
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
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
serine-type endopeptidase activity of fibrin multimer, crosslinked:tissue plasminogen activator (one-chain):plasminogen [extracellular region]
Physical Entity
Activity
This entity is regulated by
Orthologous Events
Authored