Urokinase receptor

Plasminogen activator, urokinase receptor

Rendering based on PDB 1YWH.

Available structures

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

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 19:
43.65 – 43.67 Mb

Chr 7:
24.46 – 24.48 Mb

PubMed search

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^[1] and with its native ligand, urokinase.^[2]

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.^[3]

Interactions

Urokinase receptor has been shown to interact with LRP1.^[4]

References

↑ Llinas P, Le Du MH, Gårdsvoll H, et al. (May 2005). "Crystal structure of the human urokinase plasminogen activator receptor bound to an antagonist peptide". EMBO J. 24 (9): 1655–63. doi:10.1038/sj.emboj.7600635. PMC 1142576. PMID 15861141.
↑ Huai Q, Mazar AP, Kuo A, et al. (February 2006). "Structure of human urokinase plasminogen activator in complex with its receptor". Science 311 (5761): 656–9. doi:10.1126/science.1121143. PMID 16456079.
↑ Thunø M, Macho B, Eugen-Olsen J (2009). "suPAR: the molecular crystal ball". Dis. Markers 27 (3): 157–72. doi:10.3233/DMA-2009-0657. PMID 19893210.
↑ Czekay RP, Kuemmel TA, Orlando RA, Farquhar MG (May 2001). "Direct binding of occupied urokinase receptor (uPAR) to LDL receptor-related protein is required for endocytosis of uPAR and regulation of cell surface urokinase activity". Mol. Biol. Cell 12 (5): 1467–79. doi:10.1091/mbc.12.5.1467. PMC 34598. PMID 11359936.

External links

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

Proteins: clusters of differentiation (see also list of human clusters of differentiation)

1-50	CD1 a-c 1A 1D 1E CD2 CD3 γ δ ε CD4 CD5 CD6 CD7 CD8 a CD9 CD10 CD11 a b c d CD13 CD14 CD15 CD16 A B CD18 CD19 CD20 CD21 CD22 CD23 CD24 CD25 CD26 CD27 CD28 CD29 CD30 CD31 CD32 A B CD33 CD34 CD35 CD36 CD37 CD38 CD39 CD40 CD41 CD42 a b c d CD43 CD44 CD45 CD46 CD47 CD48 CD49 a b c d e f CD50

51-100	CD51 CD52 CD53 CD54 CD55 CD56 CD57 CD58 CD59 CD61 CD62 E L P CD63 CD64 A B C CD66 a b c d e f CD68 CD69 CD70 CD71 CD72 CD73 CD74 CD78 CD79 a b CD80 CD81 CD82 CD83 CD84 CD85 a d e h j k CD86 CD87 CD88 CD89 CD90 CD91 - CD92 CD93 CD94 CD95 CD96 CD97 CD98 CD99 CD100

101-150	CD101 CD102 CD103 CD104 CD105 CD106 CD107 a b CD108 CD109 CD110 CD111 CD112 CD113 CD114 CD115 CD116 CD117 CD118 CD119 CD120 a b CD121 a b CD122 CD123 CD124 CD125 CD126 CD127 CD129 CD130 CD131 CD132 CD133 CD134 CD135 CD136 CD137 CD138 CD140b CD141 CD142 CD143 CD144 CD146 CD147 CD148 CD150

151-200	CD151 CD152 CD153 CD154 CD155 CD156 a b c CD157 CD158 (a d e i k) CD159 a c CD160 CD161 CD162 CD163 CD164 CD166 CD167 a b CD168 CD169 CD170 CD171 CD172 a b g CD174 CD177 CD178 CD179 a b CD180 CD181 CD182 CD183 CD184 CD185 CD186 CD191 CD192 CD193 CD194 CD195 CD196 CD197 CDw198 CDw199 CD200

201-250	CD201 CD202b CD204 CD205 CD206 CD207 CD208 CD209 CDw210 a b CD212 CD213a 1 2 CD217 CD218 (a b) CD220 CD221 CD222 CD223 CD224 CD225 CD226 CD227 CD228 CD229 CD230 CD233 CD234 CD235 a b CD236 CD238 CD239 CD240CE CD240D CD241 CD243 CD244 CD246 CD247 - CD248 CD249

251-300	CD252 CD253 CD254 CD256 CD257 CD258 CD261 CD262 CD263 CD264 CD265 CD266 CD267 CD268 CD269 CD271 CD272 CD273 CD274 CD275 CD276 CD278 CD279 CD280 CD281 CD282 CD283 CD284 CD286 CD288 CD289 CD290 CD292 CDw293 CD294 CD295 CD297 CD298 CD299

301-350	CD300A CD301 CD302 CD303 CD304 CD305 CD306 CD307 CD309 CD312 CD314 CD315 CD316 CD317 CD318 CD320 CD321 CD322 CD324 CD325 CD326 CD328 CD329 CD331 CD332 CD333 CD334 CD335 CD336 CD337 CD338 CD339 CD340 CD344 CD349 CD350

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