Urokinase receptor

Plasminogen activator, urokinase receptor
Rendering based on PDB 1YWH.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1YWH, 2FD6, 2I9B, 3BT1, 3BT2, 3U73, 3U74, 4K24, 4QTI
Identifiers
Symbols	PLAUR ; CD87; U-PAR; UPAR; URKR
External IDs	OMIM: 173391 MGI: 97612 HomoloGene: 48120 ChEMBL: 4883 GeneCards: PLAUR Gene
Gene ontology Molecular function • receptor activity • receptor binding • protein binding • enzyme binding • protein domain specific binding • urokinase plasminogen activator receptor activity Cellular component • endoplasmic reticulum lumen • endoplasmic reticulum membrane • plasma membrane • integral component of plasma membrane • focal adhesion • integral component of membrane • extrinsic component of membrane • anchored component of membrane • extracellular exosome • invadopodium membrane Biological process • positive regulation of protein phosphorylation • C-terminal protein lipidation • movement of cell or subcellular component • chemotaxis • signal transduction • blood coagulation • attachment of GPI anchor to protein • regulation of proteolysis • urokinase plasminogen activator signaling pathway • fibrinolysis • negative regulation of apoptotic process • positive regulation of DNA binding • post-translational protein modification • cellular protein metabolic process • positive regulation of epidermal growth factor receptor signaling pathway • positive regulation of release of cytochrome c from mitochondria • negative regulation of intrinsic apoptotic signaling pathway • negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5329	18793
Ensembl	ENSG00000011422	ENSMUSG00000046223
UniProt	Q03405	P35456
RefSeq (mRNA)	NM_001005376	NM_011113
RefSeq (protein)	NP_001005376	NP_035243
Location (UCSC)	Chr 19: 43.65 – 43.67 Mb	Chr 7: 24.46 – 24.48 Mb
PubMed search	[1]	[2]

The Urokinase receptor, also known as uPA receptor or uPAR or CD87 (Cluster of Differentiation 87), is multidomain glycoprotein tethered to the cell membrane with a glycosylphosphotidylinositol (GPI) anchor. uPAR was originally identified as a saturable binding site for urokinase on the cell surface.

Molecular characteristics

uPAR consists of three different domains of the Ly-6/uPAR/alpha-neurotoxin family. All three domains are necessary for high affinity binding of the primary ligand, urokinase. It has been possible to express uPAR recombinantly in CHO-cells and S2 cells from Drosophila melanogaster. 4 out of 5 of the possible glycosylation sites are used in vivo giving the protein a molecular weight of 50-60 kDA. Recently the structure of uPAR was solved by X-ray crystallography in complex with a peptide antagonist and with its native ligand, urokinase.

Besides the primary ligand urokinase, uPAR interacts with several other proteins, among others: vitronectin, the uPAR associated protein (uPARAP) and the integrin family of membrane proteins.

Physiological significance

uPAR is a part of the plasminogen activation system, which in the healthy body is involved in tissue reorganization events such as mammary gland involution and wound healing. In order to be able to reorganize tissue, the old tissue must be able to be degraded. An important mechanism in this degradation is the proteolysis cascade initiated by the plasminogen activation system. uPAR binds urokinase and thus restricts plasminogen activation to the immediate vicinity of the cell membrane. Thus uPAR seems to be an important player in the regulation of this process.

However the components of the plasminogen activation system have been found to be highly expressed in many malignant tumors, indicating that tumors are able to hijack the system, and use it in metastasis. Thus inhibitors of the various components of the plasminogen activation system have been sought as possible anticancer drugs.

uPAR has been involved in various other non-proteolytical processes related to cancer, such as cell migration, cell cycle regulation, and cell adhesion.

When uPA is bound to the receptor, there is cleavage between the GPI-anchor and the uPAR, releasing suPAR.

Interactions

Urokinase receptor has been shown to interact with LRP1.

See also

• Cancer
• Cluster of differentiation
• Metastasis
• Plasmin
• Plasminogen activation system
• Urokinase
• suPAR

External links

• PLAUR protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)