$VAR1 = undef;

Summary for peptidase S01.232: t-plasminogen activator

Names
MEROPS Name	t-plasminogen activator
Other names	Alteplase, Lekteplase, Reteplase, Tenecteplase, tissue plasminogen activator, tPA

Domain architecture

MEROPS Classification
Classification	Clan PA >> Subclan PA(S) >> Family S1 >> Subfamily A >> S01.232
Holotype	t-plasminogen activator (Homo sapiens), Uniprot accession P00750 (peptidase unit: 311-562), MERNUM MER0000192
History	Identifier created: Handbook of Proteolytic Enzymes (1998) Academic Press, London.

Activity
Catalytic type	Serine
Peplist	Included in the Peplist with identifier PL00320
NC-IUBMB	Subclass 3.4 (Peptidases) >> Sub-subclass 3.4.21 (Serine endopeptidases) >> Peptidase 3.4.21.68
Enzymology	BRENDA database
Proteolytic events	CutDB database (4 cleavages)
Activity status	human: active (Lijnen & Collen, 2004) mouse: active (Carmeliet et al., 1994)
Physiology	Activates plasminogen to plasmin in fibrinolysis.
Knockout	Inactivation of the t-PA gene impairs clot lysis and mice with combined t-plasminogen activator and u-plasminogen activator (S01.231) deficiency suffer extensive spontaneous fibrin deposition, with effects on growth, fertility and survival (Carmeliet et al., 1994).
Pharmaceutical relevance	Used as therapeutic thrombolytic agent.
Pathways	KEGG	Complement and coagulation cascades
	KEGG	Transcriptional misregulation in cancer
Other databases	WIKIPEDIA	http://en.wikipedia.org/wiki/Tissue_plasminogen_activator
Cleavage site specificity	Explanation of how to interpret specificity from combinatorial substrates can be found here.

Specificity from combinatorial peptides

Organism	comment	P4	P3	P2	P1	P1'	P2'	P3'	P4'	optimal substrate	fluorophore or acceptor-donor pair	Reference
Homo sapiens	recombinant	S/broad	F/Y	S/G/A	R	-	-	-	-	SFSR	ACC	Harris et al., 2000
Homo sapiens	recombinant	G	P	Y/broad	K/R	K/broad	G	G	-	GPYKKGGx	Abz-Tyr(NO2)	Kumaresan et al., 2007