Tamm–Horsfall protein
- OMIM: 191 845
- MGI: 102674
Uromodulin ( Tamm - Horsfall protein) is a protein that is excreted by the kidney into the urine. In urine, it is the protein with the highest concentration ( secretion about 50 mg / d). Uromodulin protects the kidney against kidney stone formation and urinary tract infections.
Genetics
Uromodulin is encoded by the gene UMOD.
Education
Uromodulin is synthesized in cells of the thick ascending limb of Henle's loop and via glycosyl phosphatidyl inositol (GPI) is transported to the luminal membrane. There, it is proteolytically cleaved and released into the lumen of the renal tubule.
Tasks
It is believed that Uromodulin protects the kidney against kidney stone formation and urinary tract infections. Uromodulin having immunomodulating properties, and is able to activate neutrophils and monocytes. Uromodulin activates dendritic cells via Toll - like receptor -4 ( TLR4 ) and connects so unspecific with specific immune defense.
Medical importance
Mutations in the uromodulin UMOD lead to three hereditary kidney diseases:
- Familial juvenile hyperuricemic nephropathy ( FJHM )
- Medullary cystic kidney disease type 2 ( Medullary Cystic Kidney Disease Type 2, MCKD2 ) and
- Dominant glomerulozystische kidney disease.
In particular, in adolescents, these mutations lead to inflammation ( tubulointerstitial nephritis) and increased connective tissue (fibrosis) in the renal medulla and to a decreased ability of the kidney, the urine concentrating higher. When FJHM here are elevated uric acid levels and gout in the foreground of the symptoms in the MCKD2 the formation of kidney cysts. In a genome-wide association study mutations in the gene were associated with an increased likelihood for Uromodulin of developing chronic kidney disease.
In patients with multiple myeloma may occur in the renal tubules in the presence of Tamm - Horsfall protein to precipitation of light chains in the form of protein cylinders. These precipitates have a direct toxic effect on the kidney tubule cells and can lead to a rapid loss of renal function and thus to acute renal failure ( myeloma kidney).