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Glycomics

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Description

Also known as Urine Specific Protein/ Uromucoid/ Uromodulin

A 80 kDa protein with 20% carbohydrate content. It is urine specific and can be used to confirm the nature of a suspect urine sample when urea and creatinine measurements are ambiguous.

Terminal GalNAc modifications of α2-3-sialylated structures are found on glycoproteins and on glycolipids. The former correspond to the human Sda blood group structure, and a murine oligosaccharide, termed the CT1 or CT2 antigen, first described on cytotoxic T lymphocytes (CTLs). The glycolipid-based form of this structure is known as the ganglioside GM2.(1)

The polypeptide-linked form of this structure was first identified as the pentasaccharide Siaα2-3(GalNAcβ1-4)Galβ1-4GlcNAcβ1-3Gal-, released from N-glycans present on Tamm-Horsfall glycoprotein isolated from human urine.

Uromodulin, originally identified as an immunosuppressive glycoprotein in the urine of pregnant women, has been previously shown to be identical to human Tamm-Horsfall glycoprotein (THP). THP is synthesized by the kidney and localizes to the renal thick ascending limb and early distal tubule. It is released into the urine in large quantities and thus represents a potential candidate for a protein secreted in a polarized fashion from the apical plasma membrane of epithelial cells in vivo. After introduction of the full-length cDNA encoding uromodulin/THP into HeLa, Caco-2, and Madin-Darby canine kidney cells by transfection, however, the expressed glycoprotein was almost exclusively cell-associated, as determined by immunoprecipitation after radioactive labeling of the cells.

Discussion

Human Tamm-Horsfall glycoprotein inhibits lymphocyte transformation induced by leucoagglutinin and haemagglutinin from Phaseolus vulgaris (red kidney bean). The glycoprotein interacts with the two lectins, giving insoluble precipitates. The interaction with leucoagglutinin is highly specific, and the shape of the precipitin curve is that of an antigen-antibody reaction; precipitation is specifically inhibited by N-acetyl-D-galactosamine. Results are discussed, and it is suggested that inhibition of lymphocyte transformation is due to competition between human Tamm-Horsfall glycoprotein and carbohydrate receptors on lymphocytes for the two lectins. (2)

Fluorescent labeled antibodies were used for the demonstration of uromucoid. This urine specific mucoprotein is demonstrably present only in the epithelial cells of the proximal segments of the normal human renal tubules and in the matrix of human kidney stones of all the common crystalline compositions.

Links

References


1. Essentials of Glycobiology, Varki A et al. 1999 Consortium of Glycobiology Editors, La Jolla, California

2. http://www.pubmedcentral.gov/articlerender.fcgi?artid=1161569

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