UniProt functional annotation for P00749



	UniProt functional annotation for P00749

UniProt code: P00749.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.

Catalytic activity: Reaction=Specific cleavage of Arg-|-Val bond in plasminogen to form plasmin.; EC=3.4.21.73;

Activity regulation: Inhibited by SERPINA5. {ECO:0000269|PubMed:14696115, ECO:0000269|PubMed:3501295}.

Subunit: Found in high and low molecular mass forms. Each consists of two chains, A and B. The high molecular mass form contains a long chain A which is cleaved to yield a short chain A. Forms heterodimer with SERPINA5. Binds LRP1B; binding is followed by internalization and degradation. Interacts with MRC2. Interacts with PLAUR. In complex with SERPINE1, interacts with PLAUR/uPAR (PubMed:15053742). Interacts with SORL1 and LRP1, either alone or in complex with SERPINE1; these interactions are abolished in the presence of LRPAP1/RAP (PubMed:15053742). The ternary complex composed of PLAUR-PLAU-PAI1 also interacts with SORLA (PubMed:15053742). {ECO:0000269|PubMed:10636902, ECO:0000269|PubMed:11384978, ECO:0000269|PubMed:15053742, ECO:0000269|PubMed:16456079}.

Subcellular location: Secreted {ECO:0000269|PubMed:24434139}.

Tissue specificity: Expressed in the prostate gland and prostate cancers. {ECO:0000269|PubMed:15988036}.

Ptm: Phosphorylation of Ser-158 and Ser-323 abolishes proadhesive ability but does not interfere with receptor binding. {ECO:0000269|PubMed:9151681}.

Ptm: Produced as an inactive single-chain protein (pro-uPA or sc-uPA), is processed into the active disulfide-linked two-chain form of PLAU/uPA by a proteolytic event mediated, at least, by TMPRSS4. {ECO:0000269|PubMed:24434139}.

Disease: Quebec platelet disorder (QPD) [MIM:601709]: An autosomal dominant bleeding disorder due to a gain-of-function defect in fibrinolysis. Although affected individuals do not exhibit systemic fibrinolysis, they show delayed onset bleeding after challenge, such as surgery. The hallmark of the disorder is markedly increased PLAU levels within platelets, which causes intraplatelet plasmin generation and secondary degradation of alpha-granule proteins. {ECO:0000269|PubMed:20007542}. Note=The disease is caused by variants affecting the gene represented in this entry.

Pharmaceutical: Available under the name Abbokinase (Abbott). Used in Pulmonary Embolism (PE) to initiate fibrinolysis. Clinically used for therapy of thrombolytic disorders.

Similarity: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE- ProRule:PRU00274}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.


Catalytic activity:		Reaction=Specific cleavage of Arg-\|-Val bond in plasminogen to form plasmin.; EC=3.4.21.73;
Activity regulation:		Inhibited by SERPINA5. {ECO:0000269\|PubMed:14696115, ECO:0000269\|PubMed:3501295}.
Subunit:		Found in high and low molecular mass forms. Each consists of two chains, A and B. The high molecular mass form contains a long chain A which is cleaved to yield a short chain A. Forms heterodimer with SERPINA5. Binds LRP1B; binding is followed by internalization and degradation. Interacts with MRC2. Interacts with PLAUR. In complex with SERPINE1, interacts with PLAUR/uPAR (PubMed:15053742). Interacts with SORL1 and LRP1, either alone or in complex with SERPINE1; these interactions are abolished in the presence of LRPAP1/RAP (PubMed:15053742). The ternary complex composed of PLAUR-PLAU-PAI1 also interacts with SORLA (PubMed:15053742). {ECO:0000269\|PubMed:10636902, ECO:0000269\|PubMed:11384978, ECO:0000269\|PubMed:15053742, ECO:0000269\|PubMed:16456079}.
Subcellular location:		Secreted {ECO:0000269\|PubMed:24434139}.
Tissue specificity:		Expressed in the prostate gland and prostate cancers. {ECO:0000269\|PubMed:15988036}.
Ptm:		Phosphorylation of Ser-158 and Ser-323 abolishes proadhesive ability but does not interfere with receptor binding. {ECO:0000269\|PubMed:9151681}.
Ptm:		Produced as an inactive single-chain protein (pro-uPA or sc-uPA), is processed into the active disulfide-linked two-chain form of PLAU/uPA by a proteolytic event mediated, at least, by TMPRSS4. {ECO:0000269\|PubMed:24434139}.
Disease:		Quebec platelet disorder (QPD) [MIM:601709]: An autosomal dominant bleeding disorder due to a gain-of-function defect in fibrinolysis. Although affected individuals do not exhibit systemic fibrinolysis, they show delayed onset bleeding after challenge, such as surgery. The hallmark of the disorder is markedly increased PLAU levels within platelets, which causes intraplatelet plasmin generation and secondary degradation of alpha-granule proteins. {ECO:0000269\|PubMed:20007542}. Note=The disease is caused by variants affecting the gene represented in this entry.
Pharmaceutical:		Available under the name Abbokinase (Abbott). Used in Pulmonary Embolism (PE) to initiate fibrinolysis. Clinically used for therapy of thrombolytic disorders.
Similarity:		Belongs to the peptidase S1 family. {ECO:0000255\|PROSITE- ProRule:PRU00274}.