Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.
If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.
| Class:Id | ReferenceGeneProduct:66281 |
|---|---|
| _chainChangeLog | signal peptide:1-22 added on Fri February 6 2015;propeptide:23-32 added on Fri February 6 2015;propeptide:33-35 added on Fri February 6 2015;chain:36-562 added on Fri February 6 2015;chain:36-310 added on Fri February 6 2015;chain:311-562 added on Fri February 6 2015 |
| _displayName | UniProt:P00750 PLAT |
| _timestamp | 2025-08-15 21:34:45 |
| chain | signal peptide:1-22 propeptide:23-32 propeptide:33-35 chain:36-562 chain:36-310 chain:311-562 |
| checksum | B7EC9B1A5E3FDC4D |
| comment | 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).CATALYTIC ACTIVITY Specific cleavage of Arg-|-Val bond in plasminogen to form plasmin.ACTIVITY REGULATION Inhibited by SERPINA5 (PubMed:10340997). Inhibited by SERPINE1 (PubMed:21925150).SUBUNIT Heterodimer of chain A and chain B held by a disulfide bond. Forms a heterodimer with SERPINA5. Binds to fibrin with high affinity. This interaction leads to an increase in the catalytic efficiency of the enzyme between 100-fold and 1000-fold, due to an increase in affinity for plasminogen. Similarly, binding to heparin increases the activation of plasminogen. Binds to annexin A2, cytokeratin-8, fibronectin and laminin. Binds to mannose receptor and the low-density lipoprotein receptor-related protein (LRP1); these proteins are involved in TPA clearance. Yet unidentified interactions on endothelial cells and vascular smooth muscle cells (VSMC) lead to a 100-fold stimulation of plasminogen activation. In addition, binding to VSMC reduces TPA inhibition by PAI-1 by 30-fold. Binds LRP1B; binding is followed by internalization and degradation. Interacts with SERPINE1 (PubMed:21925150). In complex with SERPINE1, interacts with SORL1 (PubMed:15053742). Interacts with apyrase from Anopheles gambiae saliva; the interaction results in PLAT activation probably via an allosteric activation mechanism (PubMed:39294191).INTERACTION Synthesized in numerous tissues (including tumors) and secreted into most extracellular body fluids, such as plasma, uterine fluid, saliva, gingival crevicular fluid, tears, seminal fluid, and milk.DOMAIN Both FN1 and one of the kringle domains are required for binding to fibrin.DOMAIN Both FN1 and EGF-like domains are important for binding to LRP1.DOMAIN The FN1 domain mediates binding to annexin A2.DOMAIN The second kringle domain is implicated in binding to cytokeratin-8 and to the endothelial cell surface binding site.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.PTM N-glycosylation of Asn-152; the bound oligomannosidic glycan is involved in the interaction with the mannose receptor.PTM Characterization of O-linked glycan was studied in Bowes melanoma cell line.DISEASE Increased activity of TPA results in increased fibrinolysis of fibrin blood clots that is associated with excessive bleeding. Defective release of TPA results in hypofibrinolysis that can lead to thrombosis or embolism.PHARMACEUTICAL Available under the names Activase (Genentech) and Retavase (Centocor and Roche) [Retavase is a fragment of TPA that contains kringle 2 and the protease domain; it was also known as BM 06.022]. Used in Acute Myocardial Infarction (AMI), in Acute Ischemic Stroke (AIS) and Pulmonary Embolism (PE) to initiate fibrinolysis.MISCELLANEOUS May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.SIMILARITY Belongs to the peptidase S1 family.ONLINE INFORMATION Tissue plasminogen activator entryONLINE INFORMATION Clinical information on Activase |
| description | recommendedName: fullName evidence="23"Tissue-type plasminogen activator shortName: t-PA shortName: t-plasminogen activator shortName: tPA ecNumber: 3.4.21.68 innNameAlteplase/innName innNameReteplase/innName component recommendedName: Tissue-type plasminogen activator chain A /component component recommendedName: Tissue-type plasminogen activator chain B /component |
| geneName | PLAT |
| identifier | P00750 |
| isSequenceChanged | FALSE |
| keyword | 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 Proteomics identification Reference proteome Repeat Secreted Serine protease Signal Zymogen |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9948485] Weiser, Joel, 2025-05-21 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 |
| name | PLAT |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8989878] ENSEMBL:ENSG00000104368 PLAT [Homo sapiens] |
| secondaryIdentifier | TPA_HUMAN A8K022 B2R8E8 Q15103 Q503B0 Q6PJA5 Q7Z7N2 Q86YK8 Q9BU99 Q9BZW1 |
| sequenceLength | 562 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:155054] UniProt:P00750-2 PLAT [Homo sapiens] [ReferenceIsoform:252321] UniProt:P00750-3 PLAT [Homo sapiens] [ReferenceIsoform:252322] UniProt:P00750-4 PLAT [Homo sapiens] [ReferenceIsoform:402232] UniProt:P00750-1 PLAT [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:158754] PLAT(36-562) [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:158758] PLAT(36-310) [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:158762] PLAT(311-562) [extracellular region] [Homo sapiens] |
| [Change default viewing format] | |