TammHorsfall protein

1

Tamm–Horsfall protein
Uromodulin
Identifiers Symbols External IDs UMOD
[1]

; ADMCKD2; FJHN; HNFJ; HNFJ1; MCKD2; THGP; THP
[2]

OMIM:  191845

MGI:  102674

[3]

HomoloGene:  2522

[4]

GeneCards: UMOD Gene

[5]

Gene Ontology Molecular function • calcium ion binding [6] Cellular component • spindle pole [7] [8] • extracellular space [9] • Golgi apparatus [10] • basolateral plasma membrane [11] • apical plasma membrane [12] • extrinsic to membrane [13] • anchored to membrane [14] • cytoplasmic vesicle [15] • membrane raft [16] • cilium membrane [17] • primary cilium Biological process • cellular defense response [19] • excretion [20] • negative regulation of cell proliferation [21] • response to organic substance [22] • chemical homeostasis [23] • metanephric ascending thin limb development • metanephric distal convoluted tubule development
[24] [18]

• metanephric thick ascending limb development [26] • regulation of ion homeostasis Sources: Amigo
[27]

[25]

/ QuickGO

[28]

RNA expression pattern

More reference expression data Orthologs Species Entrez Ensembl UniProt Human 7369
[30] [32]

[29]

Mouse 22242
[31] [33]

ENSG00000169344 P07911
[34]

ENSMUSG00000030963 Q91X17
[35]

48 Mb [43] The Tamm–Horsfall glycoprotein (THP) also known as uromodulin is a glycoprotein that in humans is encoded by the UMOD gene. These two represent the major variants of this gene and encode the same isoform.[] A role in bacterial binding and sequestration is suggested by studies showing that Escherichia coli expressing MS (mannose-sensitive) pili or fimbriae can be trapped by Tamm–Horsfall protein via its mannose-containing side chains. While several transcript variants may exist for this gene.[] Protein THP is a GPI-anchored glycoprotein.[][] Up to 150 mg/day of uromodulin may be excreted in the urine. it forms a gel. Function Uromodulin excretion in urine following proteolytic cleavage of the ectodomain of its glycophosphatidylinositol-anchored counterpart that is situated on the luminal cell surface of the loop of Henle. where uromodulin represents the 16th most concentrated one (results based on MSMS determinations). Uromodulin may act as a constitutive inhibitor of calcium crystallization in renal fluids. It is the matrix of urinary casts derived from the secretion of renal tubular cells. making it the most abundant protein in normal urine. The excretion of uromodulin in urine may provide defense against urinary tract infections caused by uropathogenic bacteria.TammHorsfall protein [36] [37] 2 RefSeq (mRNA) RefSeq (protein) NM_001008389 NP_001008390 NM_009470 NP_033496 [38] [39] Location (UCSC) Chr 16: [40] 20. It is not derived from blood plasma but is produced by the thick ascending limb of the loop of Henle of the mammalian kidney. the full-length natures of only two have been described to date.[] 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.[] When this protein is concentrated at low pH.[] . it is physiologically present in urine in large aggregates of up to several million Da. A recent list of the most abundant proteins in urine has been published (table 1 of[44]). While the monomeric molecule has a MW of approximately 68 kDa. Tamm–Horsfall protein is a high abundant protein in mammalian urine.34 – 20.46 – 119.37 Mb PubMed search [42] Chr 7: [41] 119. Gene The human UMOD gene is located on chromosome 16.

[][45] History The glycoprotein was first purified by Tamm and Horsfall from the urine of healthy individuals. org/ cgi-bin/ amigo/ go.[] Antibodies to Tamm–Horsfall protein have been seen in various forms of nephritis (e. org/ cgi-bin/ amigo/ go. nih. geneontology. but often also contain Tamm–Horsfall protein. org/ cgi-bin/ amigo/ go. cgi?view=details& search_constraint=terms& depth=0& query=GO:0010033 [22] http:/ / amigo. geneontology. gout. geneontology. org/ cgi-bin/ amigo/ go. geneontology. cgi?view=details& search_constraint=terms& depth=0& query=GO:0000922 [8] http:/ / amigo. nephrocalcin and uromodulin (this protein) are the three known urinary glycoproteins that affect the formation of calcium-containing kidney stones or calculus. geneontology. ensembl. cgi?view=details& search_constraint=terms& depth=0& query=GO:0016323 [11] http:/ / amigo. ensembl. cgi?view=details& search_constraint=terms& depth=0& query=GO:0005509 [7] http:/ / amigo. ncbi. geneontology. jax. cgi?view=details& search_constraint=terms& depth=0& query=GO:0005794 [10] http:/ / amigo. nih. geneontology. and progressive renal failure. nlm. cgi?view=details& search_constraint=terms& depth=0& query=GO:0048878 [23] http:/ / amigo. cgi?id=MGI:102674 [4] http:/ / www. ncbi. fcgi?db=gene& cmd=retrieve& dopt=default& list_uids=22242& rn=1 [32] http:/ / www. cgi?view=details& search_constraint=terms& depth=0& query=GO:0031225 [14] http:/ / amigo. cgi?view=details& search_constraint=terms& depth=0& query=GO:0006968 [19] http:/ / amigo. fcgi?db=gene& cmd=retrieve& dopt=default& list_uids=7369& rn=1 [31] http:/ / www. gov/ entrez/ query. org/ cgi-bin/ amigo/ go. cgi?gp=UniProtKB:P07911 [28] http:/ / www. nlm. cgi?view=details& search_constraint=terms& depth=0& query=GO:0008285 [21] http:/ / amigo. org/ cgi-bin/ amigo/ go. org/ cgi-bin/ amigo/ go. org/ searches/ accession_report.. org/ cgi-bin/ amigo/ go. cgi?view=details& search_constraint=terms& depth=0& query=GO:0005615 [9] http:/ / amigo. nih. org/ Homo_sapiens/ geneview?gene=ENSG00000169344. genecards. cgi?view=details& search_constraint=terms& depth=0& query=GO:0019898 [13] http:/ / amigo. org/ cgi-bin/ amigo/ go. org/ cgi-bin/ amigo/ go. geneontology. cgi?view=details& search_constraint=terms& depth=0& query=GO:0060170 [17] http:/ / amigo. These disorders are characterized by juvenile onset of hyperuricemia.[] In multiple myeloma. ebi. ac.[] It was later detected in the urine of all mammals studied. cgi?view=details& search_constraint=terms& depth=0& query=GO:0072233 [26] http:/ / amigo. cgi?view=details& search_constraint=terms& depth=0& query=GO:2000021 [27] http:/ / amigo. there is often protein cast in the distal convoluted tubule and collecting duct of the kidneys. org/ Mus_musculus/ geneview?gene=ENSMUSG00000030963. cgi?view=details& search_constraint=terms& depth=0& query=GO:0007588 [20] http:/ / amigo. php?hgnc_id=12559 [2] http:/ / omim. org/ cgi-bin/ amigo/ go. org/ cgi-bin/ amigo/ go. org/ cgi-bin/ amigo/ go. org/ cgi-bin/ amigo/ go. geneontology. pl?id_type=entrezgene& id=7369 [6] http:/ / amigo. geneontology. informatics. decreased levels of Tamm–Horsfall in urine have been found to be a good indicator of kidney stones.[] Defects in this gene are associated with the autosomal dominant renal disorders medullary cystic kidney disease-2 (MCKD2) and familial juvenile hyperuricemic nephropathy (FJHN). org/ cgi-bin/ amigo/ go. geneontology. geneontology. org/ cgi-bin/ amigo/ go. cgi?view=details& search_constraint=terms& depth=0& query=GO:0045121 [16] http:/ / amigo. geneontology. mainly consisting of immunoglobulin light chain known as Bence Jones protein. However. org/ entry/ 191845 [3] http:/ / www. cgi?view=details& search_constraint=terms& depth=0& query=GO:0016324 [12] http:/ / amigo. cgi?view=details& search_constraint=terms& depth=0& query=GO:0072372 [18] http:/ / amigo. org/ cgi-bin/ carddisp. geneontology.TammHorsfall protein 3 Clinical significance Uropontin. genenames.db=core [33] http:/ / www. cgi?view=details& search_constraint=terms& depth=0& query=GO:0031410 [15] http:/ / amigo. uk/ QuickGO/ GProtein?ac=P07911 [29] http:/ / biogps. org/ gene/ 7369/ [30] http:/ / www. org/ cgi-bin/ amigo/ go. org/ cgi-bin/ amigo/ go. cgi?view=details& search_constraint=terms& depth=0& query=GO:0072218 [24] http:/ / amigo. geneontology. Balkan nephropathy). geneontology. nlm. gov/ entrez/ query. geneontology. org/ data/ hgnc_data. geneontology. org/ cgi-bin/ amigo/ go. geneontology. org/ cgi-bin/ amigo/ go. org/ cgi-bin/ amigo/ gp-assoc. geneontology. cgi?view=details& search_constraint=terms& depth=0& query=GO:0072221 [25] http:/ / amigo. ncbi. geneontology. References [1] http:/ / www. it remains unclear whether there is any (patho-)physiologic relevance to these findings. however. org/ cgi-bin/ amigo/ go. geneontology. gov/ entrez/ query.g. fcgi?cmd=Retrieve& db=homologene& dopt=HomoloGene& list_uids=2522 [5] http:/ / www. Tamm–Horsfall protein is part of the matrix in renal calculi but a role in kidney stone formation remains debatable.db=core .

nih.gov/pubmed/8323280).1332 (http://dx.gov/pubmed/7873609).1172/JCI116920 (http://dx. Li N. Acta 1260 (3): 328–32. ncbi. Kidney Int. Biochem.260 (http://dx. • Rindler MJ. (1995). gov/ entrez/ viewer. uniprot. fcgi?val=NP_033496 http:/ / genome.gov/pubmed/8264130).org/10. Williams JD (1993). PMID  12832729 (http://www.nlm.gov/pubmed/2249987). nih. Badgett A.org/10.1006/abbi. 2011. Decker JM (1985).". doi: 10. • Muchmore AV. PMID  8323280 (http://www. Science 237 (4821): 1479–84. uniprot. Kohr WJ.nlm.". (1987).343 (http://dx.".ncbi.org/ 10. "Uromodulin (Tamm-Horsfall glycoprotein): a renal ligand for lymphokines. doi: 10. 1172/JCI116920). Connelly KG.". (1987). PMID  8264130 (http://www.1126/science. "Tamm Horsfall protein binds to a single class of carbohydrate specific receptors on human neutrophils. PMID  2409603 (http://www. • Rhodes DC.1993. 4 Further reading • Scolari F.doi. Hinsman EJ. ucsc.1993. "Towards the identification of (a) gene(s) for autosomal dominant medullary cystic kidney disease. PMID  8397318 (http://www.nlm.1126/science. gov/ sites/ entrez?db=gene& cmd=Link& LinkName=gene_pubmed& from_uid=7369 http:/ / www. nih.ncbi. Biophys.1038/ki.nlm. Decker JM.gov/pubmed/3453112).nih.nlm.ncbi.1126/ science. gov/ entrez/ viewer.nih. • Thomas DB.3498215 (http://dx. ncbi.nlm. nlm. "Uromodulin (Tamm-Horsfall glycoprotein/uromucoid) is a phosphatidylinositol-linked membrane protein. 92 (6): 2975–83.2409603 (http://dx. doi: 10. (2003).nlm.1993. org/ uniprot/ Q91X17 http:/ / www. Science 236 (4797): 83–8. • Huang ZQ. • Prasadan K. Peters JR. PMC  288501 (http://www. 44 (2): 423–9.gov/pubmed/12832729).ncbi.ncbi. "Nucleotide sequence and peptide motifs of mouse uromodulin (Tamm-Horsfall protein)--the most abundant protein in mammalian urine. et al.doi. nlm. nlm. PMID  7873609 (http://www. et al. "Uromodulin: a unique 85-kilodalton immunosuppressive glycoprotein isolated from urine of pregnant women.doi. Arch. Biochim. Nephrol.nlm. Bates J. PMID  2249987 (http:// www. Kuang WJ. PMID  3498215 (http://www. doi: 10.nih. Sanders PW (1994). (1993). fcgi?val=NM_009470 http:/ / www.gov/pmc/articles/PMC288501). nlm.gov/pubmed/2409603). doi. PMID  3453112 (http://www. nlm. .3453112). Biophys.nih. • Hession C. ncbi.org/10. ncbi.org/10. "Bence Jones proteins bind to a common peptide segment of Tamm-Horsfall glycoprotein to promote heterotypic aggregation.1993. doi: 10. Davies M. J. et al.nih.gov/ pmc/articles/PMC288501).ncbi. 304 (1): 144–53. Sherblom AP. doi: 10. J.org/10. 44 (5): 1014–21.ncbi. nih.ncbi. Viola BF. org/ uniprot/ P07911 http:/ / www.gov/pubmed/8254051). gov/ sites/ entrez?db=gene& cmd=Link& LinkName=gene_pubmed& from_uid=22242 Nagaraj et Mann. edu/ cgi-bin/ hgTracks?org=Mouse& db=mm9& position=chr7:119462866-119479255 http:/ / www.nih.".nih.1993.ncbi. Kirk KA. "Identification of human uromodulin as the Tamm-Horsfall urinary glycoprotein. 265 (34): 20784–9. edu/ cgi-bin/ hgTracks?org=Human& db=hg19& position=chr16:20344374-20367623 http:/ / genome.TammHorsfall protein [34] [35] [36] [37] [38] [39] [40] [41] [42] [43] [44] [45] http:/ / www.1993.3498215).1038/ki. Clin. Ghiggeri GM.ncbi.1038/ki. nih. Biol.".gov/pubmed/3498215). gov/ entrez/ viewer. "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. Takeo K.1126/science. et al.nlm. Kidney Int.". "Tamm-Horsfall glycoprotein binds IgG with high affinity. ncbi. nih.1126/ science. 16 (3): 321–8. PMID  8254051 (http://www.3453112 (http://dx. doi: 10. gov/ entrez/ viewer. ncbi. Chem.nlm. • Pennica D. Science 229 (4712): 479–81.1006/abbi.doi. (1991).nih. Watanabe H. fcgi?val=NM_001008389 http:/ / www. nih.org/10. PUBMED link: http:/ / www." (http://www. ncbi.nih. nlm.343).gov/pubmed/ 8397318).nih.1126/science.nih. nlm. nih.nlm. Invest.". et al.260).1038/ki. gov/ pubmed/ 21126025 Page 455 (Multiple Myeloma) in: 8th edition. fcgi?val=NP_001008390 http:/ / www.". Rhodes JA (1994).ncbi. • Fukushima K. J.doi.1332).doi. et al. Naik SS. nlm.2409603). ucsc.ncbi.

ncbi. "Localization of a gene for familial juvenile hyperuricemic nephropathy causing underexcretion-type gout to 16p12 by genome-wide linkage analysis of a large family.gov/pmc/ articles/PMC1757206). 39 (12): 882–92. J. Urol. J. "Generation and initial analysis of more than 15. (2003).39.ncbi.". Behnam R.1086/302414).nlm. et al. et al.1042/ BJ20020643).nlm.ncbi. 61 (2): 72–5.ncbi. Biochem.doi.nlm. PMID  12471200 (http://www.nlm.nih. Genet.000 full-length human and mouse cDNA sequences.gov/pmc/articles/PMC1377908).". • van Rooijen JJ.nlm. Tissier JP. Grouse LH. Medullary Cystic Kidney Disease 2 (http://www.nih.CO. doi: 10.1086/302414 (http://dx.1. "Uromodulin promoter directs high-level expression of biologically active human alpha1-antitrypsin into mouse urine. PMC  1377908 (http://www. • Pirulli D. gov/pubmed/9873244).ncbi.doi.fcgi?book=gene&part=mckd2) • OMIM entries on UMOD-Related Kidney Disease Includes: Familial Juvenile Hyperuricemic Nephropathy. "Phylogeny of Tamm-Horsfall protein.1002/1529-0131(200004)43:4<925::AID-ANR26>3.ncbi. "Mutations of the UMOD gene are responsible for medullary cystic kidney disease 2 and familial juvenile hyperuricaemic nephropathy.882).0. PMC  1222653 (http://www.882 (http://dx.nlm. PMID  11982485 (http://www.191845. PMC  139241 (http://www.nih.nih.nlm.org/10. Am.nlm.gov/pmc/articles/PMC1757206). Kumar S (1999). doi: 10.1093/glycob/9. doi: 10.org/10.CO. Voskamp AF. doi: 10. (2003). PMID  10330352 (http://www. Kamerling JP. et al. Med.nih. (2002).nih. PMID  9884403 (http://www.nlm.nih.nih. doi: 10.1136/jmg.603860. J.gov/omim/ 162000.doi.ncbi. Glycobiology 9 (1): 21–30. 99 (26): 16899–903. Soukhareva N. et al. J. Yamanaka H. PMID  10765940 (http:// www.12.gov/pmc/articles/PMC1222653). doi: 10.ncbi." (http://www. 1136/jmg.nih.nlm.org/10.ncbi. et al. Nephrol." (http://www.nlm.TammHorsfall protein • Badgett A.) 148 (Pt 4): 1193–201. Genet. 43 (4): 925–9. 365 (Pt 1): 7–11.gov/pmc/articles/PMC139241).nlm. U. • Strausberg RL.doi.603860.21). Puzzer D.gov/pmc/articles/PMC139241). Vliegenthart JF (1999). nih. "Glycosylation sites and site-specific glycosylation in human Tamm-Horsfall glycoprotein.nih.nlm.gov/pmc/articles/ PMC1222653).doi.nih. "Interaction of human Tamm-Horsfall glycoprotein with Bordetella pertussis toxin. Natl.nih.gov/bookshelf/ br. Engl. "Molecular analysis of uromodulin and SAH genes.ncbi.gov/pubmed/11932463). Acad.2-B).0.".gov/pubmed/12471200). Hum.ncbi. (2002).ncbi.gov/pubmed/ 9884403). 5 External links • GeneReviews/NCBI/NIH/UW entry on UMOD-Related Kidney Disease Includes: Familial Juvenile Hyperuricemic Nephropathy.162000.ncbi.21 (http://dx.gov/pubmed/11730273). Feingold EA. De Fusco M. et al.".nih. (2000). Debrie AS.242603899 (http://dx. Arthritis Rheum. • Zbikowska HM. positional candidates for autosomal dominant medullary cystic kidney disease linked to 16p12.nih.gov/pubmed/10330352).1159/000030292).doi.gov/pubmed/10765940).609886. Hart PS.edu/chorus/to-go/02058.gov/pubmed/11982485).ncbi.mcw. doi: 10.gov/pmc/articles/PMC1377908).nlm. Amoroso A.nlm. Proc." (http://www.609886) • Tamm–Horsfall protein deposition (http://www.1. • Menozzi FD.".ncbi.html) .org/10. PMID  11932463 (http:// www.nih.191845. 64 (6): 1655–60.nlm. Moritani M. • Hart TC. on chromosome 16p12. "Identification of a new locus for medullary cystic disease.ncbi. • Kamatani N. Gorry MC.12. PMID  11730273 (http://www.org/10. Int. PMC  1757206 (http://www. 14 (5): 392–6.1159/000030292 (http://dx. Medullary Cystic Kidney Disease 2 (http://www. Microbiology (Reading. Puzzer D.nlm. (1999).nlm.ncbi.org/10.1093/glycob/9.nih.1073/pnas.A.242603899).nlm.39. • Scolari F.org/10. Sci.gov/pubmed/12477932). PMID  9873244 (http://www.ncbi.S.1042/BJ20020643 (http://dx. PMID  12477932 (http://www." (http://www.nih.1073/ pnas.2-B (http:// dx.ncbi.1002/1529-0131(200004)43:4<925::AID-ANR26>3.doi.nih. (2002). et al.

png  Source: https://en. Dcoetzee.wikipedia.org/licenses/by-sa/3. The Anome.org/w/index. NickCT. Crystallina. Peytonbland. Boghog.0 Unported //creativecommons.Article Sources and Contributors 6 Article Sources and Contributors Tamm–Horsfall protein  Source: https://en. Vedran12. Mikael Häggström.0/ .wikipedia.murphy. Arcadian. 22 anonymous edits Image Sources. Tony1.php?title=File:PBB_GE_UMOD_206716_at_tn.png  License: GNU Free Documentation License  Contributors: - License Creative Commons Attribution-Share Alike 3.php?oldid=551285664  Contributors: Andrew Su. Tarek.org/w/index. Bobjgalindo. Giftlite. Cornwell77. Szalzala. Iamgerard. Mtnchkn. Spikey1973. Isoxyl. K. LittleWink. Licenses and Contributors file:PBB_GE_UMOD_206716_at_tn. Gcgmd.

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