Tamm-Horsfall protein

Tamm-Horsfall protein

Uromodulin, also known as UMOD, Tamm-Horsfall protein (THP), or Tamm-Horsfall mucoprotein, is a human gene.cite web | title = Entrez Gene: UMOD uromodulin (uromucoid, Tamm-Horsfall glycoprotein)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7369| accessdate = ] PBB_Summary
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summary_text = 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.cite web | title = Entrez Gene: UMOD uromodulin (uromucoid, Tamm-Horsfall glycoprotein)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7369| accessdate = ] 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.cite journal | author = Bachmann S, Mutig K, Bates J, Welker P, Geist B, Gross V, Luft FC, Alenina N, Bader M, Thiele BJ, Prasadan K, Raffi HS, Kumar S | title = Renal effects of Tamm-Horsfall protein (uromodulin) deficiency in mice | journal = Am. J. Physiol. Renal Physiol. | volume = 288 | issue = 3 | pages = F559–67 | year = 2005 | pmid = 15522986 | doi = 10.1152/ajprenal.00143.2004 | issn = ] 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.

References

Further reading

PBB_Further_reading
citations =
*cite journal | author=Scolari F, Viola BF, Ghiggeri GM, "et al." |title=Towards the identification of (a) gene(s) for autosomal dominant medullary cystic kidney disease. |journal=J. Nephrol. |volume=16 |issue= 3 |pages= 321–8 |year= 2003 |pmid= 12832729 |doi=
*cite journal | author=Rindler MJ, Naik SS, Li N, "et al." |title=Uromodulin (Tamm-Horsfall glycoprotein/uromucoid) is a phosphatidylinositol-linked membrane protein. |journal=J. Biol. Chem. |volume=265 |issue= 34 |pages= 20784–9 |year= 1991 |pmid= 2249987 |doi=
*cite journal | author=Muchmore AV, Decker JM |title=Uromodulin: a unique 85-kilodalton immunosuppressive glycoprotein isolated from urine of pregnant women. |journal=Science |volume=229 |issue= 4712 |pages= 479–81 |year= 1985 |pmid= 2409603 |doi=
*cite journal | author=Pennica D, Kohr WJ, Kuang WJ, "et al." |title=Identification of human uromodulin as the Tamm-Horsfall urinary glycoprotein. |journal=Science |volume=236 |issue= 4797 |pages= 83–8 |year= 1987 |pmid= 3453112 |doi=
*cite journal | author=Hession C, Decker JM, Sherblom AP, "et al." |title=Uromodulin (Tamm-Horsfall glycoprotein): a renal ligand for lymphokines. |journal=Science |volume=237 |issue= 4821 |pages= 1479–84 |year= 1987 |pmid= 3498215 |doi=
*cite journal | author=Prasadan K, Bates J, Badgett A, "et al." |title=Nucleotide sequence and peptide motifs of mouse uromodulin (Tamm-Horsfall protein)--the most abundant protein in mammalian urine. |journal=Biochim. Biophys. Acta |volume=1260 |issue= 3 |pages= 328–32 |year= 1995 |pmid= 7873609 |doi=
*cite journal | author=Huang ZQ, Kirk KA, Connelly KG, Sanders PW |title=Bence Jones proteins bind to a common peptide segment of Tamm-Horsfall glycoprotein to promote heterotypic aggregation. |journal=J. Clin. Invest. |volume=92 |issue= 6 |pages= 2975–83 |year= 1994 |pmid= 8254051 |doi=
*cite journal | author=Rhodes DC, Hinsman EJ, Rhodes JA |title=Tamm-Horsfall glycoprotein binds IgG with high affinity. |journal=Kidney Int. |volume=44 |issue= 5 |pages= 1014–21 |year= 1994 |pmid= 8264130 |doi=
*cite journal | author=Fukushima K, Watanabe H, Takeo K, "et al." |title=N-linked sugar chain structure of recombinant human lymphotoxin produced by CHO cells: the functional role of carbohydrate as to its lectin-like character and clearance velocity. |journal=Arch. Biochem. Biophys. |volume=304 |issue= 1 |pages= 144–53 |year= 1993 |pmid= 8323280 |doi= 10.1006/abbi.1993.1332
*cite journal | author=Jeanpierre C, Whitmore SA, Austruy E, "et al." |title=Chromosomal assignment of the uromodulin gene (UMOD) to 16p13.11. |journal=Cytogenet. Cell Genet. |volume=62 |issue= 4 |pages= 185–7 |year= 1993 |pmid= 8382593 |doi=
*cite journal | author=Thomas DB, Davies M, Peters JR, Williams JD |title=Tamm Horsfall protein binds to a single class of carbohydrate specific receptors on human neutrophils. |journal=Kidney Int. |volume=44 |issue= 2 |pages= 423–9 |year= 1993 |pmid= 8397318 |doi=
*cite journal | author=Badgett A, Kumar S |title=Phylogeny of Tamm-Horsfall protein. |journal=Urol. Int. |volume=61 |issue= 2 |pages= 72–5 |year= 1999 |pmid= 9873244 |doi=
*cite journal | author=van Rooijen JJ, Voskamp AF, Kamerling JP, Vliegenthart JF |title=Glycosylation sites and site-specific glycosylation in human Tamm-Horsfall glycoprotein. |journal=Glycobiology |volume=9 |issue= 1 |pages= 21–30 |year= 1999 |pmid= 9884403 |doi=
*cite journal | author=Scolari F, Puzzer D, Amoroso A, "et al." |title=Identification of a new locus for medullary cystic disease, on chromosome 16p12. |journal=Am. J. Hum. Genet. |volume=64 |issue= 6 |pages= 1655–60 |year= 1999 |pmid= 10330352 |doi=
*cite journal | author=Kamatani N, Moritani M, Yamanaka H, "et al." |title=Localization of a gene for familial juvenile hyperuricemic nephropathy causing underexcretion-type gout to 16p12 by genome-wide linkage analysis of a large family. |journal=Arthritis Rheum. |volume=43 |issue= 4 |pages= 925–9 |year= 2000 |pmid= 10765940 |doi= 10.1002/1529-0131(200004)43:4<925::AID-ANR26>3.0.CO;2-B |doilabel=10.1002/1529-0131(200004)43:4925::AID-ANR263.0.CO;2-B
*cite journal | author=Pirulli D, Puzzer D, De Fusco M, "et al." |title=Molecular analysis of uromodulin and SAH genes, positional candidates for autosomal dominant medullary cystic kidney disease linked to 16p12. |journal=J. Nephrol. |volume=14 |issue= 5 |pages= 392–6 |year= 2002 |pmid= 11730273 |doi=
*cite journal | author=Menozzi FD, Debrie AS, Tissier JP, "et al." |title=Interaction of human Tamm-Horsfall glycoprotein with Bordetella pertussis toxin. |journal=Microbiology (Reading, Engl.) |volume=148 |issue= Pt 4 |pages= 1193–201 |year= 2002 |pmid= 11932463 |doi=
*cite journal | author=Zbikowska HM, Soukhareva N, Behnam R, "et al." |title=Uromodulin promoter directs high-level expression of biologically active human alpha1-antitrypsin into mouse urine. |journal=Biochem. J. |volume=365 |issue= Pt 1 |pages= 7–11 |year= 2002 |pmid= 11982485 |doi= 10.1042/BJ20020643
*cite journal | author=Hart TC, Gorry MC, Hart PS, "et al." |title=Mutations of the UMOD gene are responsible for medullary cystic kidney disease 2 and familial juvenile hyperuricaemic nephropathy. |journal=J. Med. Genet. |volume=39 |issue= 12 |pages= 882–92 |year= 2003 |pmid= 12471200 |doi=
*cite journal | author=Strausberg RL, Feingold EA, Grouse LH, "et al." |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899

External links

* [http://www.mcw.edu/chorus/to-go/02058.html Tamm-Horsfall protein deposition]

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