| IED ID | IndEnz0002001709 |
| Enzyme Type ID | protease001709 |
| Protein Name |
Tissue-type plasminogen activator t-PA t-plasminogen activator tPA EC 3.4.21.68 Alteplase Reteplase Cleaved into: Tissue-type plasminogen activator chain A; Tissue-type plasminogen activator chain B |
| Gene Name | PLAT |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MDAMKRGLCCVLLLCGAVFVSPSQEIHARFRRGARSYQVICRDEKTQMIYQQHQSWLRPVLRSNRVEYCWCNSGRAQCHSVPVKSCSEPRCFNGGTCQQALYFSDFVCQCPEGFAGKCCEIDTRATCYEDQGISYRGTWSTAESGAECTNWNSSALAQKPYSGRRPDAIRLGLGNHNYCRNPDRDSKPWCYVFKAGKYSSEFCSTPACSEGNSDCYFGNGSAYRGTHSLTESGASCLPWNSMILIGKVYTAQNPSAQALGLGKHNYCRNPDGDAKPWCHVLKNRRLTWEYCDVPSCSTCGLRQYSQPQFRIKGGLFADIASHPWQAAIFAKHRRSPGERFLCGGILISSCWILSAAHCFQERFPPHHLTVILGRTYRVVPGEEEQKFEVEKYIVHKEFDDDTYDNDIALLQLKSDSSRCAQESSVVRTVCLPPADLQLPDWTECELSGYGKHEALSPFYSERLKEAHVRLYPSSRCTSQHLLNRTVTDNMLCAGDTRSGGPQANLHDACQGDSGGPLVCLNDGRMTLVGIISWGLGCGQKDVPGVYTKVTNYLDWIRDNMRP |
| Enzyme Length | 562 |
| Uniprot Accession Number | P00750 |
| Absorption | |
| Active Site | ACT_SITE 357; /note=Charge relay system; /evidence=ECO:0000305|PubMed:8613982; ACT_SITE 406; /note=Charge relay system; /evidence=ECO:0000305|PubMed:8613982; ACT_SITE 513; /note=Charge relay system; /evidence=ECO:0000305|PubMed:8613982 |
| Activity Regulation | ACTIVITY REGULATION: Inhibited by SERPINA5. {ECO:0000269|PubMed:10340997}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Specific cleavage of Arg-|-Val bond in plasminogen to form plasmin.; EC=3.4.21.68; |
| DNA Binding | |
| EC Number | 3.4.21.68 |
| Enzyme Function | FUNCTION: Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single Arg-Val bond in plasminogen. By controlling plasmin-mediated proteolysis, it plays an important role in tissue remodeling and degradation, in cell migration and many other physiopathological events. During oocyte activation, plays a role in cortical granule reaction in the zona reaction, which contributes to the block to polyspermy (By similarity). {ECO:0000250|UniProtKB:P19637}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Alternative sequence (5); Beta strand (39); Chain (3); Disulfide bond (17); Domain (5); Glycosylation (4); Helix (8); Natural variant (4); Propeptide (2); Region (1); Sequence conflict (6); Signal peptide (1); Site (4); Turn (2) |
| Keywords | 3D-structure;Alternative splicing;Cleavage on pair of basic residues;Direct protein sequencing;Disulfide bond;EGF-like domain;Glycoprotein;Hydrolase;Kringle;Pharmaceutical;Plasminogen activation;Protease;Reference proteome;Repeat;Secreted;Serine protease;Signal;Zymogen |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted, extracellular space. |
| Modified Residue | |
| Post Translational Modification | PTM: The single chain, almost fully active enzyme, can be further processed into a two-chain fully active form by a cleavage after Arg-310 catalyzed by plasmin, tissue kallikrein or factor Xa.; PTM: Differential cell-specific N-linked glycosylation gives rise to two glycoforms, type I (glycosylated at Asn-219) and type II (not glycosylated at Asn-219). The single chain type I glycoform is less readily converted into the two-chain form by plasmin, and the two-chain type I glycoform has a lower activity than the two-chain type II glycoform in the presence of fibrin. {ECO:0000269|PubMed:1900431}.; PTM: N-glycosylation of Asn-152; the bound oligomannosidic glycan is involved in the interaction with the mannose receptor. {ECO:0000269|PubMed:1900431}.; PTM: Characterization of O-linked glycan was studied in Bowes melanoma cell line. {ECO:0000269|PubMed:1900431}. |
| Signal Peptide | SIGNAL 1..22; /evidence=ECO:0000269|Ref.20 |
| Structure 3D | NMR spectroscopy (4); X-ray crystallography (7) |
| Cross Reference PDB | 1A5H; 1BDA; 1PK2; 1PML; 1RTF; 1TPG; 1TPK; 1TPM; 1TPN; 5BRR; 5ZLZ; |
| Mapped Pubmed ID | 10959683; 11385207; 11848437; 12589088; 12891381; 15207811; 15448144; 15542697; 16836660; 17608581; 19730683; 19897580; 22449964; 2318848; 23193360; 23483454; 24506586; 2496749; 2503541; 26324706; 29329714; 2962641; 3103680; 3126346; 7199524; 8069221; 9268299; 9886297; |
| Motif | |
| Gene Encoded By | |
| Mass | 62,917 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda | 3.4.21.68; |