Urokinase receptor (original) (raw)

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Mammalian protein found in Homo sapiens

PLAUR
Available structuresPDBOrtholog search: PDBe RCSB List of PDB id codes1YWH, 2FD6, 3BT1, 3BT2, 3U73, 3U74, 2I9B, 4K24, 4QTI
Identifiers
Aliases PLAUR, CD87, U-PAR, UPAR, URKR, plasminogen activator, urokinase receptor
External IDs OMIM: 173391; MGI: 97612; HomoloGene: 48120; GeneCards: PLAUR; OMA:PLAUR - orthologs
Gene location (Human)Chromosome 19 (human)Chr.Chromosome 19 (human)[1]Chromosome 19 (human)Genomic location for PLAURGenomic location for PLAURBand19q13.31Start43,646,095 bp[1]End43,670,547 bp[1]
Gene location (Mouse)Chromosome 7 (mouse)Chr.Chromosome 7 (mouse)[2]Chromosome 7 (mouse)Genomic location for PLAURGenomic location for PLAURBand7|7 A3Start24,161,909 bp[2]End24,175,393 bp[2]
RNA expression patternBgeeHuman Mouse (ortholog)Top expressed inperiodontal fibermonocytestromal cell of endometriumvena cavagallbladderbloodbone marrow cellscartilage tissuegranulocyteright lungTop expressed ingranulocytedeciduaendothelial cell of lymphatic vesseltibiofemoral jointright lung lobebone marrowcalvariastroma of bone marrowmucous cell of stomachspleenMore reference expression dataBioGPSMore reference expression data
Gene ontologyMolecular function protein domain specific binding protein binding urokinase plasminogen activator receptor activity enzyme binding signaling receptor binding signaling receptor activity Cellular component integral component of membrane cell projection endoplasmic reticulum lumen endoplasmic reticulum membrane membrane focal adhesion integral component of plasma membrane extracellular region cell junction anchored component of membrane extracellular exosome extrinsic component of membrane plasma membrane specific granule membrane cell surface Biological process positive regulation of protein phosphorylation negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway fibrinolysis negative regulation of intrinsic apoptotic signaling pathway urokinase plasminogen activator signaling pathway negative regulation of apoptotic process blood coagulation attachment of GPI anchor to protein chemotaxis positive regulation of release of cytochrome c from mitochondria positive regulation of DNA binding positive regulation of epidermal growth factor receptor signaling pathway regulation of proteolysis signal transduction neutrophil degranulation Sources:Amigo / QuickGO
OrthologsSpeciesHuman MouseEntrez532918793EnsemblENSG00000011422ENSMUSG00000046223UniProtQ03405P35456RefSeq (mRNA)NM_001005376NM_001005377NM_001301037NM_002659NM_011113RefSeq (protein)NP_001005376NP_001005377NP_001287966NP_002650NP_035243Location (UCSC)Chr 19: 43.65 – 43.67 MbChr 7: 24.16 – 24.18 MbPubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

Molecular characteristics

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uPAR consists of three tandem LU domains, which are protein domains of the three-finger protein family.[5] The structure of uPAR has been solved by X-ray crystallography in complex with a peptide antagonist[6] and with its native ligand, urokinase.[7] All three three-finger domains are necessary for high affinity binding of the primary ligand, urokinase. In addition, uPAR also interacts with several other proteins, including vitronectin, the uPAR associated protein (uPARAP) and the integrin family of membrane proteins.

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.

Physiological significance

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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. When urokinase is bound to the receptor, there is cleavage between the GPI-anchor and the uPAR, releasing a soluble form of the protein known as suPAR.[8][9]

Clinical significance

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Soluble urokinase plasminogen activator receptor (suPAR) has been found to be a biomarker of inflammation.[10] Elevated suPAR is seen in chronic obstructive pulmonary disease, asthma, liver failure, heart failure, cardiovascular disease, and rheumatoid arthritis.[10] Smokers have significantly higher suPAR compared to non-smokers.[10]

Urokinase receptors have been found to be highly expressed on senescent cells, leading researchers to use chimeric antigen receptor T cells to eliminate senescent cells in mice.[11][12]

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.[13]

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

Urokinase receptor has been shown to interact with LRP1.[14]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000011422 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000046223 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Kessler, Pascal; Marchot, Pascale; Silva, Marcela; Servent, Denis (August 2017). "The three-finger toxin fold: a multifunctional structural scaffold able to modulate cholinergic functions". Journal of Neurochemistry. 142: 7–18. doi:10.1111/jnc.13975. PMID 28326549.
  6. ^ Llinas P, Le Du MH, Gårdsvoll H, Danø K, Ploug M, Gilquin B, Stura EA, Ménez A (May 2005). "Crystal structure of the human urokinase plasminogen activator receptor bound to an antagonist peptide". The EMBO Journal. 24 (9): 1655–63. doi:10.1038/sj.emboj.7600635. PMC 1142576. PMID 15861141.
  7. ^ Huai Q, Mazar AP, Kuo A, Parry GC, Shaw DE, Callahan J, Li Y, Yuan C, Bian C, Chen L, Furie B, Furie BC, Cines DB, Huang M (February 2006). "Structure of human urokinase plasminogen activator in complex with its receptor". Science. 311 (5761): 656–9. Bibcode:2006Sci...311..656H. doi:10.1126/science.1121143. PMID 16456079. S2CID 39521660.
  8. ^ ViroGates. "What is suPAR". suPARnostic® by ViroGates. Retrieved 2021-09-27.
  9. ^ Thunø M, Macho B, Eugen-Olsen J (2009). "suPAR: the molecular crystal ball". Disease Markers. 27 (3): 157–72. doi:10.1155/2009/504294. PMC 3835059. PMID 19893210.
  10. ^ a b c Desmedt S, Desmedt V, Delanghe JR, Speeckaert R, Speeckaert MM (2017). "The Intriguing Role of Soluble Urokinase Receptor in Inflammatory Diseases". Critical Reviews in Clinical Laboratory Sciences. 54 (2): 117–133. doi:10.1080/10408363.2016.1269310. PMID 28084848. S2CID 32624995.
  11. ^ Wagner V, Gil J (2020). "T Cells Engineered to Target Senescence". Nature. 583 (7814): 37–38. Bibcode:2020Natur.583...37W. doi:10.1038/d41586-020-01759-x. hdl:10044/1/80980. PMID 32601490.
  12. ^ Amor C, Feucht J, Lowe SW (2020). "Senolytic CAR T cells reverse senescence-associated pathologies". Nature. 583 (7814): 127–132. doi:10.1038/s41586-020-2403-9. PMC 7583560. PMID 32555459.
  13. ^ Josip Madunić (2018). "The Urokinase Plasminogen Activator System in Human Cancers: An Overview of Its Prognostic and Predictive Role". Thrombosis and Haemostasis. 118 (12): 2020–2036. doi:10.1055/s-0038-1675399. PMID 30419600.
  14. ^ 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". Molecular Biology of the Cell. 12 (5): 1467–79. doi:10.1091/mbc.12.5.1467. PMC 34598. PMID 11359936.