Tamm-Horsfall protein

Uromodulin, also known as UMOD, Tamm-Horsfall protein (THP), or Tamm-Horsfall mucoprotein, is a human gene.

THP is a GPI-anchored glycoprotein which is not derived from blood plasma, but is produced by the thick ascending limb of the loop of Henle of mammalian kidney. While the monomeric molecule has a MW of approx. 68 kD, it is physiologically present in a highly agrregated state in urine. When this protein is concentrated at low pH, it forms gel. Tamm-Horsfall protein is the most abundant protein in mammalian urine. It is the matrix of urinary casts derived from the secretion of renal tubular cells.

Uropontin, nephrocalcin and uromodulin are the 3 known urinary glycoproteins that affect the formation of calcium-containing kidney stones or calculus.

The protein was first purified by Tamm and Horsfall from the urine of healthy individuals (Tamms I & Horsfall FL, 1950). It was later detected in the urine of all mammals studied.

The function of THP is not well understood. Studies using THP deficient mice revealed that THP may have a role in regulatory physiology and actually participates in transporter function. A role in bacterial binding and sequestration is suggested by studies showing that E.coli expressing MS (mannose-sensitive) pili or fimbriae can be trapped by Tamm-Horsfall protein via its mannose-containing side chains. Tamm-Horsfall protein is part of the matrix in renal calculi but a role in kidney stone formation remains debatable. Antibodies to Tamm-Horsfall protein have been seen in various forms of nephritis (eg, Balkan nephropathy), however, it remains unclear whether there is any (patho-)physiologic relevance to these findings.