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

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Structure Literature 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
TREEFAMhttp://www.treefam.org/family/TF329901
PANTHERhttp://www.pantherdb.org/panther/familyList.do?searchType=basic&fieldName=all&listType=6&fieldValue=PTHR24264:SF38
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)
weblogo
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
Relevant inhibitors PKSI-527, tranexamic acid
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