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urokinase; urokinase-type plasminogen activator; U-plasminogen activator; uPA (PLAU)
Function:
- proteolytic enzyme produced naturally by the renal parenchymal cells that promotes thrombolysis by converting plasminogen to plasmin
- specific cleavage of Arg-|-Val bond in plasminogen to form plasmin
- inhibited by SERPINA5
- phosphorylation of Ser-158 & Ser-323 abolishes proadhesive ability but does not interfere with receptor binding
- found in high & low molecular mass forms
- each consists of two chains, A & 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 & degradation
- interacts with MRC2
- interacts with PLAUR
Structure:
- belongs to the peptidase S1 family
- contains 1 EGF-like domain
- contains 1 kringle domain
- contains 1 peptidase S1 domain
Compartment:
- secreted
- normally present in urine
Alternative splicing: named isoforms=2
Expression:
- secreted by renal parenchymal cells
- expressed in the prostate gland & prostate cancers
Pathology:
- defects in PLAU are the cause of Quebec platelet disorder
Pharmacology:
- available under the name Abbokinase (Abbott)
- used for therapy of venous thrombosis or venous thromboembolism
Interactions
molecular events
Related
urokinase plasminogen activator surface receptor; uPAR; U-PAR; monocyte activation antigen Mo3; CD87 (PLAUR, MO3, UPAR)
Specific
Abbokinase (urokinase)
prourokinase; contains: urokinase-type plasminogen activator long chain A; urokinase-type plasminogen activator short chain A; urokinase-type plasminogen activator chain B (PLAU)
urokinase A fragment
urokinase B fragment
Urokinase Parenteral
General
enzymatic agent
fibrinolytic agent (thrombolytic agent)
glycoprotein
multisubunit protein
peptide precursor
phosphoprotein
plasminogen activator
Properties
SIZE: entity length = 431 aa
MW = 49 kD
MOTIF: signal sequence {1-20}
EGF domain {27-63}
MOTIF: cysteine residue {C31}
MODIFICATION: cysteine residue {C39}
cysteine residue {C33}
MODIFICATION: cysteine residue {C51}
PLAUR binding {34-57}
Thr glycosylation site {T38}
cysteine residue {C39}
MODIFICATION: cysteine residue {C31}
cysteine residue {C51}
MODIFICATION: cysteine residue {C33}
cysteine residue {C53}
MODIFICATION: cysteine residue {C62}
cysteine residue {C62}
MODIFICATION: cysteine residue {C53}
Kringle {70-151}
MOTIF: cysteine residue {C70}
MODIFICATION: cysteine residue {C151}
cysteine residue {C91}
MODIFICATION: cysteine residue {C133}
cysteine residue {C122}
MODIFICATION: cysteine residue {C146}
cysteine residue {C133}
MODIFICATION: cysteine residue {C91}
cysteine residue {C146}
MODIFICATION: cysteine residue {C122}
cysteine residue {C151}
MODIFICATION: cysteine residue {C70}
Connecting peptide {152-177}
MOTIF: Ser phosphorylation site {S158}
cysteine residue {C168}
MODIFICATION: cysteine residue {C-INTERCHAIN}
proteolytic site {177-178}
S1 domain {179-424}
MOTIF: cysteine residue {C209}
MODIFICATION: cysteine residue {C225}
cysteine residue {C217}
MODIFICATION: cysteine residue {C288}
histidine residue {H224}
cysteine residue {C225}
MODIFICATION: cysteine residue {C209}
aspartate residue {D275}
cysteine residue {C288}
MODIFICATION: cysteine residue {C217}
cysteine residue {C313}
MODIFICATION: cysteine residue {C382}
N-glycosylation site {N322}
Ser phosphorylation site {S323}
cysteine residue {C345}
MODIFICATION: cysteine residue {C361}
cysteine residue {C361}
MODIFICATION: cysteine residue {C345}
cysteine residue {C372}
MODIFICATION: cysteine residue {C400}
serine residue {S376}
cysteine residue {C382}
MODIFICATION: cysteine residue {C313}
cysteine residue {C400}
MODIFICATION: cysteine residue {C372}
MISC-INFO: elimination route LIVER
KIDNEY
1/2life 10-20 MINUTES
Database Correlations
OMIM correlations
MORBIDMAP 191840
UniProt P00749
PFAM correlations
Entrez Gene 5328
Kegg hsa:5328
ENZYME 3.4.21.73
References
- Clinical Diagnosis and Management by Laboratory Methods,
18th ed, J.B. Henry (ed), W.B. Saunders, Philadelphia,
PA, 1991 pg 739
- UniProt :accession P00749
- Wikipedia; Note: urokinase entry
http://en.wikipedia.org/wiki/urokinase
- SeattleSNPs
http://pga.gs.washington.edu/data/plau/