Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

3.4.21.73

Official Name

u-plasminogen activator

Name from literature

urokinase

Pathway from literature

cleavage of the preactivation peptide from the NH2 terminus of native plasminogen( NH2-terminal glutamic acid )

Pathway from KEGG

Cellular Processes; Immune System; Complement and coagulation cascades; map04610

Organisms

Human (9606)

Genome localization

10q24[5328 ],

Comments

Formed from the inactive precursor by action of plasmin or plasma kallikrein. Differs in structure from t-plasminogen activator (EC 3.4.21.68), and does not bind to fibrin. In peptidase family S1 (trypsin family). Formerly included in EC 3.4.21.31 and EC 3.4.99.26

Rate-limiting Description

"Stage 1 is maximally enhanced (75-fold) at either 0.0025 M epsilon-aminocaproic acid or 0.025 M lysine and occurs 4 times more rapidly than Stage 2, which becomes the rate-limiting step at these concentrations." (1150667)

"Bound plasminogen is rate-limiting for cell-surface-mediated activation of plasminogen by urokinase." (7639718)

"In the catalyzed hydrolysis of ZAlaONp, in the absence of acetamidine or ethylamine, the acylation step (k2) is rate limiting all over the pH range from 3 to 8." (7046788)

Regulatory Information

Upstream transcription factor

1432;7157;6720;4052

Regulatory type

Detail

key enzyme;

"The attempts to identify initiation routes for activation of the proform of the key enzyme urokinase-type plasminogen activator (pro-uPA) in vivo have been hampered by the strong activator potency of the plasmin, that is generated during the progress of the cascade." (10642175#9626349#9816042)

transcriptional level;"TNF-alpha(7124),p53(7157)"

"observations confirm a new role for p53 as a uPA mRNA binding protein that down-regulates uPA mRNA stability and decreases cellular uPA expression" (18390474#18177545)

phosphorylation;PKC alpha

"Protein kinase C-dependent in vivo phosphorylation of prourokinase leads to the formation of a receptor competitive antagonist." (9765311)

signal pathway;"TGF-beta1(4052),PI3 kinase"

"uPA is upregulated by TGF-beta1 and PI3 kinase in human tumor cells" (14597629)

signal pathway;p38(1432)

"participates in endothelial cell migration under regulation of p38 MAPK pathway" (15371454)

others;Bcl-xL anti-apoptotic factor()

"incubation of retinal pigment epithelial cells with uPA elicits a time-dependent enhancement of MAPK and phosphatidylinositol 3-kinase activities as well as the transcriptional activation of Bcl-xL anti-apoptotic factor" (16632475)

signal pathway;

"uPA gene regulation by c-phycocyanin (c-pc) is transcriptionally controlled through cAMP mediated PKA pathway." (17029796)

signal pathway;p38(1432)

"Upregulation of urokinase type plasminogen activator (UroPA) expression during early development of knee osteoarthritis (OA) occurs via MAPK ERK, JNK, and p38 signaling pathways and the PI3K signaling pathway in cultured cells debrided from OA knees." (17299841)

transcriptional factor;SREBP-1(6720)

"Urokinase plasminogen activator (uPA) stimulates cholesterol biosynthesis in macrophages through activation of SREBP-1 in a PI3-kinase and MEK-dependent manner" (17681345)

phosphorylation;

P00749

phosphorylation;

P00749:from_uniprot:158_Phosphoserine

phosphorylation;

P00749:from_uniprot:323_Phosphoserine

Gene ontology

Gene ontology

GO:0042730 (P) fibrinolysis [P00749 ];
GO:0006508 (P) proteolysis [P00749 ];
GO:0005576 (C) extracellular region [P00749 ];
GO:0006935 (P) chemotaxis [P00749 ];
GO:0005886 (C) plasma membrane [P00749 ];
GO:0007165 (P) signal transduction [P00749 ];
GO:0004252 (F) serine-type endopeptidase activity [P00749 ];

Tissue expression

Tissue From HPRD

Serum [01883 ];
Intestinal epithelium [01883 ];
Bronchial epithelial cell [01883 ];
Smooth muscle [01883 ];
Mammary gland [01883 ];
Aorta [01883 ];
Lung [01883 ];
Placenta [01883 ];
Umbilical vein endothelial cell [01883 ];
Vascular endothelium [01883 ];
Brain [01883 ];
Keratinocyte [01883 ];

Tissue specificity

Expressed in the prostate gland and prostate cancers [P00749 ];

Subcellular localization

Localization

extracellular [P00749 ];

Links

SwissProt

P00749

Entrez Gene

5328

HPRD

01883



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  Last Modified: 2009-03-24  
  Design by Zhao Min