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uromodulin; Tamm-Horsfall urinary glycoprotein; THP (UMOD)

Function: - most abundant protein in human urine - function unknown - may function to bind bacteria through its mannose-containing residues, preventing bacterial colonization of the uroepithelium - may play a role in regulating the circulating activity of cytokines as it binds to IL-1, IL-2 & TNF with high affinity Structure: - glycoprotein - contains 3 EGF-like domains - contains 1 ZP domain Compartment: - cell membrane; lipid-anchor, GPI-anchor - secreted after cleavage into the urine Alternative splicing: named isoforms=3 Expression: - produced by cells of the ascending loop of Henle & the adjacent distal convoluted tubule of the kidney - most abundant protein in human urine Pathology: - uromodulin is the primary constituent of hyaline casts - defects in UMOD are the cause of: a) familial juvenile hyperuricemic nephropathy b) medullary cystic kidney disease 2 - defects in UMOD are a cause of glomerulocystic kidney disease with hyperuricemia & isosthenuria

General

glypiated protein

Properties

SIZE: entity length = 640 aa MW = 70 kD COMPARTMENT: plasma membrane CELL-REGION: apical region CELL: epithelial cell MOTIF: signal sequence {1-24} EGF domain {28-64} MOTIF: cysteine residue {C32} MODIFICATION: cysteine residue {C41} cysteine residue {C35} MODIFICATION: cysteine residue {C50} N-glycosylation site {N38} cysteine residue {C41} MODIFICATION: cysteine residue {C32} cysteine residue {C50} MODIFICATION: cysteine residue {C35} cysteine residue {C52} MODIFICATION: cysteine residue {C63} cysteine residue {C63} MODIFICATION: cysteine residue {C52} EGF domain {65-107} MOTIF: cysteine residue {C69} MODIFICATION: cysteine residue {C83} N-glycosylation site {N76} cysteine residue {C77} MODIFICATION: cysteine residue {C92} N-glycosylation site {N80} cysteine residue {C83} MODIFICATION: cysteine residue {C69} cysteine residue {C92} MODIFICATION: cysteine residue {C77} cysteine residue {C94} MODIFICATION: cysteine residue {C106} cysteine residue {C106} MODIFICATION: cysteine residue {C94} EGF domain {108-149} MOTIF: cysteine residue {C112} MODIFICATION: cysteine residue {C126} cysteine residue {C120} MODIFICATION: cysteine residue {C135} cysteine residue {C126} MODIFICATION: cysteine residue {C112} cysteine residue {C135} MODIFICATION: cysteine residue {C120} cysteine residue {C137} MODIFICATION: cysteine residue {C148} cysteine residue {C148} MODIFICATION: cysteine residue {C137} N-glycosylation site {N232} N-glycosylation site {N275} N-glycosylation site {N322} ZP domain {334-589} MOTIF: cysteine residue {*1} MODIFICATION: cysteine residue {*2} cysteine residue {*2} MODIFICATION: cysteine residue {*1} N-glycosylation site {N396} glycosyl phosphatidylinositol [GPI] membrane anchor {N614}

Database Correlations

OMIM correlations MORBIDMAP 191845 UniProt P07911 PFAM correlations Entrez Gene 7369 Kegg hsa:7369

References

  1. UniProt :accession P07911
  2. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=UMOD
  3. Entrez Gene :accession 7369
  4. Trudu M, Janas S, Lanzani C et al Common noncoding UMOD gene variants induce salt-sensitive hypertension and kidney damage by increasing uromodulin expression. Nat Med. 2013 Dec;19(12):1655-60. PMID: 24185693 Free PMC Article