Description: Homo sapiens uromodulin (UMOD), transcript variant 2, mRNA. RefSeq Summary (NM_001008389): The protein encoded by this gene is the most abundant protein in mammalian urine under physiological conditions. 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. This protein may act as a constitutive inhibitor of calcium crystallization in renal fluids. Excretion of this protein in urine may provide defense against urinary tract infections caused by uropathogenic bacteria. Defects in this gene are associated with the renal disorders medullary cystic kidney disease-2 (MCKD2), glomerulocystic kidney disease with hyperuricemia and isosthenuria (GCKDHI), and familial juvenile hyperuricemic nephropathy (FJHN). Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2013]. Transcript (Including UTRs) Position: hg19 chr16:20,344,373-20,364,037 Size: 19,665 Total Exon Count: 11 Strand: - Coding Region Position: hg19 chr16:20,344,636-20,362,059 Size: 17,424 Coding Exon Count: 10
ID:UROM_HUMAN DESCRIPTION: RecName: Full=Uromodulin; AltName: Full=Tamm-Horsfall urinary glycoprotein; Short=THP; Contains: RecName: Full=Uromodulin, secreted form; Flags: Precursor; FUNCTION: Uromodulin: Functions in biogenesis and organization of the apical membrane of epithelial cells of the thick ascending limb of Henle's loop (TALH), where it promotes formation of complex filamentous gel-like structure providing the water barrier permeability. May serve as a receptor for binding and endocytosis for cytokines (IL-1, IL-2) and TNF. Facilitates neutrophil migration across renal epithelial. FUNCTION: Uromodulin, secreted form: Secreted into urine after proteolytically cleaveage. Into the urine, may contribute to colloid osmotic pressure, retards passage of positively charged electrolytes, prevents urinary tract infection and modulates formation of supersaturated salts and their crystals. SUBCELLULAR LOCATION: Apical cell membrane; Lipid-anchor, GPI- anchor. Basolateral cell membrane; Lipid-anchor, GPI-anchor. Cell projection, cilium membrane. Note=Only a small fraction is sort to the basolateral pole of tubular epithelial cells compared to apical localization. Secreted into urine after cleavage. Colocalized with NPHP1 and KIF3A. SUBCELLULAR LOCATION: Uromodulin, secreted form: Secreted. TISSUE SPECIFICITY: Synthesized exclusively in the kidney. Expressed exclusively by epithelial cells of the thick ascending limb of Henle's loop (TALH) and of distal convoluted tubule lumen. Most abundant protein in normal urine. DOMAIN: The ZP domain is involved in the polymerization of the protein to promote the formation of complex gel-like structure. PTM: N-glycosylated. N-glycan heterogeneity at Asn-232: Hex7HexNAc6 (major) and dHex1Hex7HexNAc6 (minor); at Asn-322: dHex1Hex6HexNAc5 (minor), dHex1Hex7HexNAc6 (major) and dHex1Hex8HexNAc7 (minor); at Asn-396: Hex6HexNAc5 (major), dHex1Hex6HexNAc5 (minor) and Hex7HexNAc6 (minor). PTM: Proteolytically cleaved at a conserved C-terminal proteolytic cleavage site to generate the secreted form found into urine. DISEASE: Defects in UMOD are the cause of familial juvenile hyperuricemic nephropathy type 1 (HNFJ1) [MIM:162000]. HNFJ1 is a renal disease characterized by juvenil onset of hyperuricemia, polyuria, progressive renal failure, and gout. The disease is associated with interstitial pathological changes resulting in fibrosis. DISEASE: Defects in UMOD are the cause of medullary cystic kidney disease type 2 (MCKD2) [MIM:603860]. MCKD2 is a form of tubulointerstitial nephropathy characterized by formation of renal cysts at the corticomedullary junction. It is characterized by adult onset of impaired renal function and salt wasting resulting in end-stage renal failure by the sixth decade. DISEASE: Defects in UMOD are the cause of glomerulocystic kidney disease with hyperuricemia and isosthenuria (GCKDHI) [MIM:609886]. GCKDHI is a renal disorder characterized by a cystic dilation of Bowman space, a collapse of glomerular tuft, and hyperuricemia due to low fractional excretion of uric acid and severe impairment of urine concentrating ability. MISCELLANEOUS: A specific, but as yet unidentified, protease(s) cleaves off and releases UMOD into urine. SIMILARITY: Contains 3 EGF-like domains. SIMILARITY: Contains 1 ZP domain. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/UMOD";
Creatinine Anna Kottgen et al. Nature genetics 2009, Multiple loci associated with indices of renal function and chronic kidney disease., Nature genetics.
[PubMed 19430482]
Hypertension Sandosh Padmanabhan et al. PLoS genetics 2010, Genome-wide association study of blood pressure extremes identifies variant near UMOD associated with hypertension., PLoS genetics.
[PubMed 21082022]
Kidney Diseases Anna Kottgen et al. Nature genetics 2010, New loci associated with kidney function and chronic kidney disease., Nature genetics.
[PubMed 20383146]
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P07911
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
M17778 - Human uromodulin (Tamm-Horsfall glycoprotein) mRNA, complete cds. AK127643 - Homo sapiens cDNA FLJ45741 fis, clone KIDNE2015987, highly similar to Uromodulin precursor. AK055722 - Homo sapiens cDNA FLJ31160 fis, clone KIDNE1000015, highly similar to UROMODULIN PRECURSOR. AK091961 - Homo sapiens cDNA FLJ34642 fis, clone KIDNE2016918, highly similar to UROMODULIN PRECURSOR. AK096043 - Homo sapiens cDNA FLJ38724 fis, clone KIDNE2010151, highly similar to UROMODULIN PRECURSOR. AX747279 - Sequence 804 from Patent EP1308459. M15881 - Human uromodulin (Tamm-Horsfall glycoprotein) mRNA, complete cds. AK127648 - Homo sapiens cDNA FLJ45746 fis, clone KIDNE2018727, highly similar to Uromodulin precursor. BC035975 - Homo sapiens uromodulin, mRNA (cDNA clone MGC:32619 IMAGE:4556427), complete cds. JD075690 - Sequence 56714 from Patent EP1572962. JD402899 - Sequence 383923 from Patent EP1572962. JD537622 - Sequence 518646 from Patent EP1572962. JD231069 - Sequence 212093 from Patent EP1572962. JD277850 - Sequence 258874 from Patent EP1572962. JD251636 - Sequence 232660 from Patent EP1572962. AB590834 - Synthetic construct DNA, clone: pFN21AE2038, Homo sapiens UMOD gene for uromodulin, without stop codon, in Flexi system. JD020697 - Sequence 1721 from Patent EP1572962. JD033330 - Sequence 14354 from Patent EP1572962. CU690246 - Synthetic construct Homo sapiens gateway clone IMAGE:100022010 5' read UMOD mRNA. JD079103 - Sequence 60127 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein P07911 (Reactome details) participates in the following event(s):
R-HSA-8855954 B4GALNT2 transfers GalNAc from UDP-GalNAc to Sial-Gal-GlcNAc-Gal to form the Sd(a) antigen on UMOD R-HSA-446203 Asparagine N-linked glycosylation R-HSA-597592 Post-translational protein modification R-HSA-392499 Metabolism of proteins