PLAT

Domain

Both FN1 and one of the kringle domains are required for binding to fibrin.

Both FN1 and EGF-like domains are important for binding to LRP1.

The FN1 domain mediates binding to annexin A2.

The second kringle domain is implicated in binding to cytokeratin-8 and to the endothelial cell surface binding site.

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).

Involvement in 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.

Post-translational modifications

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.

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.

N-glycosylation of Asn-152; the bound oligomannosidic glycan is involved in the interaction with the mannose receptor.

Characterization of O-linked glycan was studied in Bowes melanoma cell line.

Sequence similarities

Belongs to the peptidase S1 family.

Tissue specificity

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.

Cellular localization

• Secreted
• Extracellular space

Alternative names

• Tissue-type plasminogen activator
• t-PA
• t-plasminogen activator
• tPA
• PLAT

Database links

• entrezGene:5327
• entrezGene:5054
• omim:173360
• omim:173370
• swissprot:P00750
• swissprot:P05121

Target type

Proteins

Primary research area

Cardiovascular

Molecular weight

62917Da