UMOD Antibody – Rabbit Polyclonal

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]

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. Ref.10Uromodulin, 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. Ref.10

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. Ref.8 Ref.9 Ref.10 Ref.11Uromodulin, secreted form: Secreted Ref.8 Ref.10 Ref.11.

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. Ref.8

Domain: The ZP domain is involved in the polymerization of the protein to promote the formation of complex gel-like structure.

Post-translational modification: 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). Ref.12Proteolytically cleaved at a conserved C-terminal proteolytic cleavage site to generate the secreted form found into urine. Ref.7

Involvement in disease: Familial juvenile hyperuricemic nephropathy 1 (HNFJ1) [MIM:162000]: A renal disease characterized by juvenile onset of hyperuricemia, polyuria, progressive renal failure, and gout. The disease is associated with interstitial pathological changes resulting in fibrosis.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3 Ref.13 Ref.15Medullary cystic kidney disease 2 (MCKD2) [MIM:603860]: 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.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3 Ref.14 Ref.16Glomerulocystic kidney disease with hyperuricemia and isosthenuria (GCKDHI) [MIM:609886]: 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.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14

Miscellaneous: A specific, but as yet unidentified, protease(s) cleaves off and releases UMOD into urine.

Sequence similarities: Contains 3 EGF-like domains.Contains 1 ZP domain.