Tamm-Horsfall protein

Uromodulin (uromucoid, Tamm-Horsfall glycoprotein)
Identifiers
Symbol(s)	UMOD; FJHN; ADMCKD2; HNFJ; MCKD2; THGP
External IDs	OMIM: 191845 MGI: 102674 Homologene: 2522
Gene Ontology Molecular Function: • calcium ion binding • GPI anchor binding Cellular Component: • extracellular space • membrane • extrinsic to membrane Biological Process: • cellular defense response • negative regulation of cell proliferation
RNA expression pattern
Additional recommended knowledge Essential Laboratory Skills Guide Weighing the right way Guide to balance cleaning: 8 simple steps More reference expression data
Orthologs
	Human	Mouse
Entrez	7369	22242
Ensembl	ENSG00000169344	ENSMUSG00000030963
Uniprot	P07911	Q8CJA0
Refseq	NM_001008389 (mRNA) NP_001008390 (protein)	NM_009470 (mRNA) NP_033496 (protein)
Location	Chr 16: 20.25 - 20.27 Mb	Chr 7: 119.25 - 119.27 Mb
Pubmed search	[1]	[2]

Uromodulin, also known as UMOD, Tamm-Horsfall protein (THP), or Tamm-Horsfall mucoprotein, is a human gene.^[1]

This gene encodes uromodulin, the most abundant protein in normal urine. Its excretion in urine follows proteolytic cleavage of the ectodomain of its glycosyl phosphatidylinosital-anchored counterpart that is situated on the luminal cell surface of the loop of Henle. Uromodulin may act as a constitutive inhibitor of calcium crystallization in renal fluids. Excretion of uromodulin in urine may provide defense against urinary tract infections caused by uropathogenic bacteria. Defects in this gene are associated with the autosomal dominant renal disorders medullary cystic kidney disease-2 (MCKD2) and familial juvenile hyperuricemic nephropathy (FJHN). These disorders are characterized by juvenile onset of hyperuricemia, gout, and progressive renal failure. While several transcript variants may exist for this gene, the full-length natures of only two have been described to date. These two represent the major variants of this gene and encode the same isoform.^[1]

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 [3]. 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.

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Further reading