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

Urokinase

Urokinase , also called urokinase-type plasminogen activator , is a serine protease . Urokinase was originally isolated from human urine, but is present in several physiological locations, such as blood stream and the extracellular matrix...

. suPAR results from the cleavage and release of membrane-bound uPAR. suPAR concentration positively correlates to the activation level of the immune system

Immune system

An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

 and is present in plasma

Blood plasma

Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...

, urine

Urine

Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...

, blood

Blood

Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....

, serum

Blood serum

In blood, the serum is the component that is neither a blood cell nor a clotting factor; it is the blood plasma with the fibrinogens removed...

, and cerebrospinal fluid

Cerebrospinal fluid

Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...

.

Molecular characteristics

suPAR has a secondary structure of 17 anti parallel β-sheets with 3 short α-helices

Alpha helix

A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...

. 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

Primary structure

The primary structure of peptides and proteins refers to the linear sequence of its amino acid structural units. The term "primary structure" was first coined by Linderstrøm-Lang in 1951...

 and tertiary

Tertiary structure

In biochemistry and molecular biology, the tertiary structure of a protein or any other macromolecule is its three-dimensional structure, as defined by the atomic coordinates.-Relationship to primary structure:...

 structure, causing its distinct ligand binding properties.

The GPI-anchor links uPAR to the cell membrane making it available for uPA

Urokinase

Urokinase , also called urokinase-type plasminogen activator , is a serine protease . Urokinase was originally isolated from human urine, but is present in several physiological locations, such as blood stream and the extracellular matrix...

 binding. When uPA is bound to the receptor, there is cleavage between the GPI-anchor and DIII, forming suPAR. 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.

Application

suPAR is a biomarker for activation of the inflammatory

Inflammation

Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

 and immune systems. suPAR levels are positively correlated with pro-inflammatory biomarkers, such as tumor necrosis factor-α, leukocyte counts, and C-reactive protein

C-reactive protein

C-reactive protein is a protein found in the blood, the levels of which rise in response to inflammation...

. Elevated levels of suPAR are associated with increased risk of systemic inflammatory response syndrome

Systemic inflammatory response syndrome

Systemic inflammatory response syndrome is an inflammatory state affecting the whole body, frequently a response of the immune system to infection, but not necessarily so...

 (SIRS), cancer

Cancer

Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

, cardiovascular disease

Cardiovascular disease

Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...

, type 2 diabetes, infectious diseases, HIV

HIV

Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...

, and mortality

Mortality rate

Mortality rate is a measure of the number of deaths in a population, scaled to the size of that population, per unit time...

. suPARnostic

Suparnostic

suPARnostic is a simplified double monoclonal antibody sandwich enzyme-linked immunosorbent assay that measures the amount of soluble urokinase plasminogen activator receptor in blood. Elevated plasma suPAR levels have been observed in various infectious, inflammatory and autoimmune diseases...

is a prognostic test used to detect suPAR levels in blood plasma.