Summary for peptidase S01.232: t-plasminogen activator

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Structure Literature Substrates Inhibitors Pharma


MEROPS Namet-plasminogen activator
Other namesAlteplase, Lekteplase, Reteplase, Tenecteplase, tissue plasminogen activator, tPA
Domain architecture
MEROPS Classification
Classification Clan PA >> Subclan PA(S) >> Family S1 >> Subfamily A >> S01.232
Holotypet-plasminogen activator (Homo sapiens), Uniprot accession P00750 (peptidase unit: 311-562), MERNUM MER0000192
History Identifier created: Handbook of Proteolytic Enzymes (1998) Academic Press, London.
Catalytic typeSerine
PeplistIncluded in the Peplist with identifier PL00320
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.21 (Serine endopeptidases) >> Peptidase
EnzymologyBRENDA database
Proteolytic eventsCutDB database (4 cleavages)
Activity statushuman: active (Lijnen & Collen, 2004)
mouse: active (Carmeliet et al., 1994)
PhysiologyActivates plasminogen to plasmin in fibrinolysis.
KnockoutInactivation 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 relevanceUsed as therapeutic thrombolytic agent.
Pathways KEGGComplement and coagulation cascades
KEGGTranscriptional misregulation in cancer
Other databases WIKIPEDIA
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 - GPYK+KGGx Abz-Tyr(NO2) Kumaresan et al., 2007
Relevant inhibitors DX-9065a
Human genetics
Gene symbol Locus Megabases Ensembl Entrez gene Gene Cards OMIM
PLAT 8p12 ENSG00000104368 5327 PLAT 173370
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
Plat 8:A2 ENSMUSG00000031538 18791 MGI:97610