background:
May play a role in regulating the circulating activity of cytokines as it binds to IL-1, IL-2 and TNF with high affinity.
Tissue specificity:Synthesized by kidney. Most abundant protein in normal human urine.
Involvement in disease:Defects in UMOD are the cause of familial juvenile hyperuricemic nephropathy type 1 (HNFJ1) . 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.
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.
his gene encodes uromodulin, the most abundant protein innormal urine. Its excretion in urine follows proteolytic cleavageof the ectodomain of its glycosyl phosphatidylinosital-anchoredcounterpart that is situated on the luminal cell surface of theloop of Henle. Uromodulin may act as a constitutive inhibitor ofcalcium crystallization in renal fluids. Excretion of uromodulin inurine may provide defense against urinary tract infections causedby uropathogenic bacteria. Defects in this gene are associated withthe autosomal dominant renal disorders medullary cystic kidneydisease-2 (MCKD2) and familial juvenile hyperuricemic nephropathy(FJHN). These disorders are characterized by juvenile onset ofhyperuricemia, gout, and progressive renal failure. While severaltranscript variants may exist for this gene, the full-lengthnatures of only two have been described to date. These tworepresent the major variants of this gene and encode the sameisoform.
Function:
Uromodulin: Functions in biogenesis and organization ofthe apical membrane of epithelial cells of the thick ascending limbof Henle's loop (TALH), where it promotes formation of complexfilamentous gel-like structure providing the water barrierpermeability. May serve as a receptor for binding and endocytosisfor cytokines (IL-1, IL-2) and TNF. Facilitates neutrophilmigration across renal epithelial.
Uromodulin, secreted form: Secreted into urine afterproteolytically cleaveage. Into the urine, may contribute tocolloid osmotic pressure, retards passage of positively chargedelectrolytes, prevents urinary tract infection and modulatesformation 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 issort to the basolateral pole of tubular epithelial cells comparedto apical localization. Secreted into urine after cleavage.Colocalized with NPHP1 and KIF3A.
Uromodulin, secreted form: Secreted.
Tissue Specificity:
Synthesized exclusively in the kidney.Expressed exclusively by epithelial cells of the thick ascendinglimb of Henle's loop (TALH) and of distal convoluted tubule lumen.Most abundant protein in normal urine.
Post-translational modifications:
N-glycosylated. N-glycan heterogeneity at Asn-232:Hex7HexNAc6 (major) and dHex1Hex7HexNAc6 (minor); at Asn-322:dHex1Hex6HexNAc5 (minor), dHex1Hex7HexNAc6 (major) anddHex1Hex8HexNAc7 (minor); at Asn-396: Hex6HexNAc5 (major),dHex1Hex6HexNAc5 (minor) and Hex7HexNAc6 (minor).
Proteolytically cleaved at a conserved SLCterminal proteolyticcleavage site to generate the secreted form found into urine.
DISEASE:
Defects in UMOD are the cause of familial juvenilehyperuricemic nephropathy type 1 (HNFJ1) [MIM:162000]. HNFJ1 is arenal disease characterized by juvenil onset of hyperuricemia,polyuria, progressive renal failure, and gout. The disease isassociated with interstitial pathological changes resulting infibrosis.
Defects in UMOD are the cause of medullary cystic kidneydisease type 2 (MCKD2) [MIM:603860]. MCKD2 is a form oftubulointerstitial nephropathy characterized by formation of renalcysts at the corticomedullary junction. It is characterized byadult onset of impaired renal function and salt wasting resultingin end-stage renal failure by the sixth decade.
Defects in UMOD are the cause of glomerulocystic kidneydisease with hyperuricemia and isosthenuria (GCKDHI) [MIM:609886].GCKDHI is a renal disorder characterized by a cystic dilation ofBowman space, a collapse of glomerular tuft, and hyperuricemia dueto low fractional excretion of uric acid and severe impairment ofurine concentrating ability.
Similarity:
Contains 3 EGF-like domains.
Contains 1 ZP domain.
Database links:
UniProtKB/Swiss-Prot: P07911.1
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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