PLAU

Plasminogen activator, urokinase

PDB rendering based on 1c5w.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes

1C5W, 1C5X, 1C5Y, 1C5Z, 1EJN, 1F5K, 1F5L, 1F92, 1FV9, 1GI7, 1GI8, 1GI9, 1GJ7, 1GJ8, 1GJ9, 1GJA, 1GJB, 1GJC, 1GJD, 1KDU, 1LMW, 1O3P, 1O5A, 1O5B, 1O5C, 1OWD, 1OWE, 1OWH, 1OWI, 1OWJ, 1OWK, 1SC8, 1SQA, 1SQO, 1SQT, 1U6Q, 1URK, 1VJ9, 1VJA, 1W0Z, 1W10, 1W11, 1W12, 1W13, 1W14, 2FD6, 2I9A, 2I9B, 2NWN, 2O8T, 2O8U, 2O8W, 2R2W, 2VIN, 2VIO, 2VIP, 2VIQ, 2VIV, 2VIW, 2VNT, 3BT1, 3BT2, 3IG6, 3KGP, 3KHV, 3KID, 3M61, 3MHW, 3MWI, 3OX7, 3OY5, 3OY6, 3PB1, 3QN7, 3U73, 4DVA, 4DW2, 4FU7, 4FU8, 4FU9, 4FUB, 4FUC, 4FUD, 4FUE, 4FUF, 4FUG, 4FUH, 4FUI, 4FUJ, 4GLY, 4H42, 4JK5, 4JK6, 4JNI, 4JNL, 4K24, 4MNV, 4MNW, 4MNX, 4MNY, 4OS1, 4OS2, 4OS4, 4OS5, 4OS6, 4OS7, 4X1N, 4X1Q, 4X1R

Identifiers

Symbols

PLAU ; ATF; BDPLT5; QPD; UPA; URK; u-PA

External IDs

OMIM: 191840 MGI: 97611 HomoloGene: 55670 ChEMBL: 3286 GeneCards: PLAU Gene

EC number

3.4.21.73

Gene ontology
Molecular function	• serine-type endopeptidase activity • protein binding
Cellular component	• extracellular region • extracellular space • plasma membrane • focal adhesion • cell surface • extracellular exosome
Biological process	• angiogenesis • proteolysis • chemotaxis • signal transduction • spermatogenesis • embryo implantation • blood coagulation • positive regulation of cell proliferation • regulation of receptor activity • response to activity • smooth muscle cell migration • regulation of smooth muscle cell migration • positive regulation of smooth muscle cell migration • plasminogen activation • regulation of cell adhesion mediated by integrin • cellular response to hepatocyte growth factor stimulus • fibrinolysis • skeletal muscle tissue regeneration • response to hyperoxia • positive regulation of ovulation • regulation of wound healing • neuron death • cellular response to lipopolysaccharide • cellular response to glucose stimulus • cellular response to hypoxia • cellular response to fluid shear stress • cellular response to staurosporine • regulation of smooth muscle cell-matrix adhesion • regulation of hepatocyte proliferation • positive regulation of reactive oxygen species metabolic process
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 10:
73.91 – 73.92 Mb

Chr 14:
20.84 – 20.84 Mb

PubMed search

Urokinase-type plasminogen activator is an enzyme that in humans is encoded by the PLAU gene.^[1]

Function

This gene encodes a serine protease involved in degradation of the extracellular matrix and possibly tumor cell migration and proliferation. A specific polymorphism in this gene may be associated with late-onset Alzheimer disease and also with decreased affinity for fibrin-binding. The protein encoded by this gene converts plasminogen to plasmin by specific cleavage of an Arg-Val bond in plasminogen. This gene's proprotein is cleaved at a Lys-Ile bond by plasmin to form a two-chain derivative in which a single disulfide bond connects the amino-terminal A-chain to the catalytically active, carboxy-terminal B-chain. This two-chain derivative is also called HMW-uPA (high molecular weight uPA). HMW-uPA can be further processed into LMW-uPA (low molecular weight uPA) by cleavage of chain A into a short chain A (A1) and an amino-terminal fragment. LMW-uPA is proteolytically active but does not bind to the uPA receptor.^[2]

Interactions

PLAU has been shown to interact with Protein C inhibitor.^[3]^[4]

References

↑ Nagai M, Hiramatsu R, Kanéda T, Hayasuke N, Arimura H, Nishida M, Suyama T (Dec 1985). "Molecular cloning of cDNA coding for human preprourokinase". Gene 36 (1-2): 183–8. doi:10.1016/0378-1119(85)90084-8. PMID 2415429.
↑ "Entrez Gene: PLAU plasminogen activator, urokinase".
↑ Geiger M, Huber K, Wojta J, Stingl L, Espana F, Griffin JH, Binder BR (Aug 1989). "Complex formation between urokinase and plasma protein C inhibitor in vitro and in vivo". Blood 74 (2): 722–8. PMID 2752144.
↑ España F, Berrettini M, Griffin JH (Aug 1989). "Purification and characterization of plasma protein C inhibitor". Thromb. Res. 55 (3): 369–84. doi:10.1016/0049-3848(89)90069-8. PMID 2551064.

Ploug M, Gårdsvoll H, Jørgensen TJ, Lønborg Hansen L, Danø K (2002). "Structural analysis of the interaction between urokinase-type plasminogen activator and its receptor: a potential target for anti-invasive cancer therapy.". Biochem. Soc. Trans. 30 (2): 177–83. doi:10.1042/BST0300177. PMID 12023847.
Alfano M, Sidenius N, Blasi F, Poli G (2004). "The role of urokinase-type plasminogen activator (uPA)/uPA receptor in HIV-1 infection.". J. Leukoc. Biol. 74 (5): 750–6. doi:10.1189/jlb.0403176. PMID 12960238.
Harbeck N, Kates RE, Gauger K, Willems A, Kiechle M, Magdolen V, Schmitt M (2004). "Urokinase-type plasminogen activator (uPA) and its inhibitor PAI-I: novel tumor-derived factors with a high prognostic and predictive impact in breast cancer.". Thromb. Haemost. 91 (3): 450–6. doi:10.1160/TH03-12-0798. PMID 14983219.
Gilabert-Estelles J, Ramon LA, España F, Gilabert J, Castello R, Estelles A (2006). "Expression of the fibrinolytic components in endometriosis.". Pathophysiol. Haemost. Thromb. 35 (1-2): 136–40. doi:10.1159/000093556. PMID 16855359.

PDB gallery

1c5w: STRUCTURAL BASIS FOR SELECTIVITY OF A SMALL MOLECULE, S1-BINDING, SUB-MICROMOLAR INHIBITOR OF UROKINASE TYPE PLASMINOGEN ACTIVATOR

1c5x: STRUCTURAL BASIS FOR SELECTIVITY OF A SMALL MOLECULE, S1-BINDING, SUB-MICROMOLAR INHIBITOR OF UROKINASE TYPE PLASMINOGEN ACTIVATOR

1c5y: STRUCTURAL BASIS FOR SELECTIVITY OF A SMALL MOLECULE, S1-BINDING, SUB-MICROMOLAR INHIBITOR OF UROKINASE TYPE PLASMINOGEN ACTIVATOR

1c5z: STRUCTURAL BASIS FOR SELECTIVITY OF A SMALL MOLECULE, S1-BINDING, SUB-MICROMOLAR INHIBITOR OF UROKINASE TYPE PLASMINOGEN ACTIVATOR

1ejn: UROKINASE PLASMINOGEN ACTIVATOR B-CHAIN INHIBITOR COMPLEX

1f5k: UROKINASE PLASMINOGEN ACTIVATOR B-CHAIN-BENZAMIDINE COMPLEX

1f5l: UROKINASE PLASMINOGEN ACTIVATOR B-CHAIN-AMILORIDE COMPLEX

1f92: UROKINASE PLASMINOGEN ACTIVATOR B CHAIN-UKI-1D COMPLEX

1fv9: Crystal structure of human microurokinase in complex with 2-amino-5-hydroxy-benzimidazole

1gi7: A NOVEL SERINE PROTEASE INHIBITION MOTIF INVOLVING A MULTI-CENTERED SHORT HYDROGEN BONDING NETWORK AT THE ACTIVE SITE

1gi8: A NOVEL SERINE PROTEASE INHIBITION MOTIF INVOLVING A MULTI-CENTERED SHORT HYDROGEN BONDING NETWORK AT THE ACTIVE SITE

1gi9: A NOVEL SERINE PROTEASE INHIBITION MOTIF INVOLVING A MULTI-CENTERED SHORT HYDROGEN BONDING NETWORK AT THE ACTIVE SITE

1gj7: ENGINEERING INHIBITORS HIGHLY SELECTIVE FOR THE S1 SITES OF SER190 TRYPSIN-LIKE SERINE PROTEASE DRUG TARGETS

1gj8: ENGINEERING INHIBITORS HIGHLY SELECTIVE FOR THE S1 SITES OF SER190 TRYPSIN-LIKE SERINE PROTEASE DRUG TARGETS

1gj9: ENGINEERING INHIBITORS HIGHLY SELECTIVE FOR THE S1 SITES OF SER190 TRYPSIN-LIKE SERINE PROTEASE DRUG TARGETS

1gja: ENGINEERING INHIBITORS HIGHLY SELECTIVE FOR THE S1 SITES OF SER190 TRYPSIN-LIKE SERINE PROTEASE DRUG TARGETS

1gjb: ENGINEERING INHIBITORS HIGHLY SELECTIVE FOR THE S1 SITES OF SER190 TRYPSIN-LIKE SERINE PROTEASE DRUG TARGETS

1gjc: ENGINEERING INHIBITORS HIGHLY SELECTIVE FOR THE S1 SITES OF SER190 TRYPSIN-LIKE SERINE PROTEASE DRUG TARGETS

1gjd: ENGINEERING INHIBITORS HIGHLY SELECTIVE FOR THE S1 SITES OF SER190 TRYPSIN-LIKE SERINE PROTEASE DRUG TARGETS

1kdu: SEQUENTIAL 1H NMR ASSIGNMENTS AND SECONDARY STRUCTURE OF THE KRINGLE DOMAIN FROM UROKINASE

1lmw: LMW U-PA STRUCTURE COMPLEXED WITH EGRCMK (GLU-GLY-ARG CHLOROMETHYL KETONE)

1o3p: Elaborate Manifold of Short Hydrogen Bond Arrays Mediating Binding of Active Site-Directed Serine Protease Inhibitors

1o5a: Dissecting and Designing Inhibitor Selectivity Determinants at the S1 site Using an Artificial Ala190 Protease (Ala190 uPA)

1o5b: Dissecting and Designing Inhibitor Selectivity Determinants at the S1 site Using an Artificial Ala190 Protease (Ala190 uPA)

1o5c: Dissecting and Designing Inhibitor Selectivity Determinants at the S1 site Using an Artificial Ala190 Protease (Ala190 uPA)

1owd: Substituted 2-Naphthamidine inhibitors of urokinase

1owe: Substituted 2-Naphthamidine inhibitors of urokinase

1owh: Substituted 2-Naphthamidine Inhibitors of Urokinase

1owi: Substituted 2-Naphthamidine Inhibitors of Urokinase

1owj: Substituted 2-Naphthamidine Inhibitors of Urokinase

1owk: Substituted 2-Naphthamidine Inhibitors of Urokinase

1sc8: Urokinase Plasminogen Activator B-Chain-J435 Complex

1sqa: Substituted 2-Naphthamidine Inhibitors of Urokinase

1sqo: Substituted 2-Naphthamidine Inhibitors of Urokinase

1sqt: Substituted 2-Naphthamidine Inhibitors of Urokinase

1u6q: Substituted 2-Naphthamadine inhibitors of Urokinase

1urk: SOLUTION STRUCTURE OF THE AMINO TERMINAL FRAGMENT OF UROKINASE-TYPE PLASMINOGEN ACTIVATOR

1vj9: Urokinase Plasminogen Activator B-Chain-JT464 Complex

1vja: Urokinase Plasminogen Activator B-Chain-JT464 Complex

2fd6: Structure of Human Urokinase Plasminogen Activator in Complex with Urokinase Receptor and an anti-upar antibody at 1.9 A

2i9a: Crystal structure of the free aminoterminal fragment of urokinase type plasminogen activator (ATF)

2i9b: Crystal structure of ATF-urokinase receptor complex

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PLAU

Function

Interactions

References

Further reading