Summary for peptidase S01.231: urokinase-type plasminogen activator

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Structure Literature Human EST Substrates Inhibitors Pharma

 

Names
MEROPS Nameurokinase-type plasminogen activator
Other namescellular plasminogen activator, u-plasminogen activator, urinary plasminogen activator, uPA, urokinase
Domain architecture
MEROPS Classification
Classification Clan PA >> Subclan PA(S) >> Family S1 >> Subfamily A >> S01.231
Holotypeurokinase-type plasminogen activator (Homo sapiens), Uniprot accession P00749 (peptidase unit: 179-431), MERNUM MER0000195
History Identifier created: Handbook of Proteolytic Enzymes (1998) Academic Press, London.
Activity
Catalytic typeSerine
PeplistIncluded in the Peplist with identifier PL00319
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.21 (Serine endopeptidases) >> Peptidase 3.4.21.73
EnzymologyBRENDA database
Proteolytic eventsCutDB database (7 cleavages)
Activity statushuman: active (Ellis, 2004)
mouse: active (Skriver et al., 1982)
InhibitorsNot trapped by alpha-2-macroglobulin (Barrett 1981).
PhysiologyActivates plasminogen to plasmin in fibrinolysis.
KnockoutKnockout mice appear to be normal when maintained under ideal, non-stressful conditions, but show a variety of abnormalities, including a peculiar predisposition to a rare bacterial infection (Shapiro et al., 1997). Mice with combined t-plasminogen activator (S01.232) and u-plasminogen activator deficiency suffer extensive spontaneous fibrin deposition, with effects on growth, fertility and survival (Carmeliet et al., 1994).
Pharmaceutical relevanceIt has been reported that down-regulation of expression of both cathepsin B and u-plasminogen activator has anti-tumour activity in experimental systems (Gondi et al., 2004).
Pathways KEGGComplement and coagulation cascades
KEGGMicroRNAs in cancer
KEGGProteoglycans in cancer
KEGGTranscriptional misregulation in cancer
Other databases WIKIPEDIAhttp://en.wikipedia.org/wiki/Urokinase
Cleavage site specificity Explanations of how to interpret the following cleavage site sequence logo and specificity matrix can be found here.
Cleavage pattern-/s/gs/RkScissile bond-/rv/-/- (based on 17 cleavages)
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Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 0 2 7 0 2 0 2 3
Pro 2 1 0 0 0 1 0 0
Ala 2 0 1 0 1 0 1 0
Val 1 0 0 1 2 3 1 1
Leu 0 1 1 0 0 1 0 1
Ile 0 1 0 0 2 0 0 0
Met 0 0 0 0 0 0 0 0
Phe 0 0 0 0 0 1 0 1
Tyr 0 1 0 0 1 1 2 1
Trp 0 0 0 0 0 0 0 0
Ser 1 5 5 0 1 0 1 0
Thr 1 1 0 0 0 0 2 0
Cys 1 0 0 0 0 0 0 0
Asn 1 0 1 0 0 0 1 2
Gln 0 1 0 0 0 0 0 0
Asp 0 0 0 0 0 0 0 0
Glu 0 0 0 0 0 0 0 0
Lys 2 0 1 4 0 0 0 0
Arg 1 0 0 12 1 3 0 0
His 0 0 0 0 0 0 0 1
Human genetics
Gene symbol Locus Megabases Ensembl Entrez gene Gene Cards OMIM
PLAU 10q24 ENSG00000122861 5328 PLAU 191840
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
Plau 14:A2 ENSMUSG00000021822 18792 MGI:97611