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SuPAR

suPAR, soluble urokinase-type plasminogen activator receptor, (NCBI Accession no. AAK31795) is the soluble form of uPAR. uPAR is a membrane bound receptor for uPA, otherwise known as urokinase as well as Vitronectin. suPAR results from the cleavage and release of membrane-bound uPAR. suPAR concentration positively correlates to the activation level of the immune system and is present in plasma, urine, blood, serum, and cerebrospinal fluid. suPAR is a marker of disease severity and aggressiveness.[1]

Molecular characteristics

suPAR has a secondary structure of 17 anti parallel β-sheets with 3 short α-helices. There are three homologous domains of suPAR: DI, DII, and DIII. In the comparison of cDNA sequences, DI differs from DII and DIII in its primary and tertiary structure, causing its distinct ligand binding properties.[1][2]

The GPI-anchor links uPAR to the cell membrane making it available for uPA binding. When uPA is bound to the receptor, there is cleavage between the GPI-anchor and DIII, forming suPAR.[3] There are three different suPAR forms: suPARI-III, suPARII-III, and suPARI. Of these three forms suPARII-III is known to be a chemotactic agent for promoting the immune system.[1]

Application

suPAR is a biomarker for activation of the inflammatory and immune systems. suPAR levels are positively correlated with pro-inflammatory biomarkers, such as tumor necrosis factor-α, leukocyte counts, and C-reactive protein. It has also been associated with organ damage in various diseases.[4][5][6] Elevated levels of suPAR are associated with increased risk of systemic inflammatory response syndrome (SIRS), cancer, Focal segmental glomerulosclerosis, cardiovascular disease, type 2 diabetes, infectious diseases, HIV, and mortality.[7] suPARnostic is a prognostic test used to detect suPAR levels in blood plasma.

References

  1. ^ a b c Thunø, Maria; Macho, Betina; Eugen-Olsen, Jesper (2009). "SuPAR: The Molecular Crystal Ball". Disease Markers. 27: 157–72. doi:10.1155/2009/504294. 
  2. ^ M. Huang, A. P. Mazar, G. Parry, A. A.-R. “Higazi, A. Kuo and D. B. Cines. Crystallization of soluble urokinase receptor (suPAR) in complex with urokinase amino-terminal fragment (1-143)”. Acta Crystallographica (2005): D61 (6), 697-700.
  3. ^ "What is suPAR? | Quick Links". Suparnostic.com. Retrieved 2012-05-09. 
  4. ^ Enocsson, Helena; Wetterö, Jonas; Skogh, Thomas; Sjöwall, Christopher (2013). "Soluble urokinase plasminogen activator receptor levels reflect organ damage in systemic lupus erythematosus". Translational Research. 162 (5): 287–296. doi:10.1016/j.trsl.2013.07.003. PMID 23916811. 
  5. ^ Sjöwall, C; Martinsson, K; Cardell, K; Ekstedt, M; Kechagias, S (2014). "Soluble urokinase plasminogen activator receptor levels are associated with severity of fibrosis in non-alcoholic fatty liver disease". Translational Research. 165 (6): 658–66. doi:10.1016/j.trsl.2014.09.007. PMID 25445207. 
  6. ^ Hahm, E; et. al. (Dec 2016). "Bone marrow-derived immature myeloid cells are a main source of circulating suPAR contributing to proteinuric kidney disease". Nature Medicine. doi:10.1038/nm.4242. PMID 27941791. 
  7. ^ Eugen-Olsen, J. et al. "Circulating Soluble Urokinase Plasminogen Activator Receptor Predicts Cancer, Cardiovascular Disease, Diabetes and Mortality in the General Population."Journal of Internal Medicine (2010).