Tamm–Horsfall protein

Tamm-Horsfall proteinUMODuromodulinfamilial juvenile hyperuricemic nephropathyTamm–HorsfallTamm–Horsfall mucoprotein
The Tamm–Horsfall glycoprotein (THP), also known as uromodulin, is a glycoprotein that in humans is encoded by the UMOD gene.wikipedia
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Urinary cast

urinary castscastsRBC casts
It is the matrix of urinary casts derived from the secretion of renal tubular cells.
They form via precipitation of Tamm–Horsfall mucoprotein which is secreted by renal tubule cells, and sometimes also by albumin in conditions of proteinuria.

Kidney

kidneysrenalkidney disorder
It is not derived from blood plasma but is produced by the thick ascending limb of the loop of Henle of the mammalian kidney.
The highest expressed kidney specific protein is uromodulin, the most abundant protein in urine with functions that prevent calcification and growth of bacteria.

Ascending limb of loop of Henle

thick ascending limbthin ascending limbthick ascending limb of loop of Henle
It is not derived from blood plasma but is produced by the thick ascending limb of the loop of Henle of the mammalian kidney.
This is also the part of the tubule that generates Tamm-Horsfall protein.

Kidney stone disease

kidney stonekidney stonesnephrolithiasis
Uropontin, nephrocalcin and uromodulin (this protein) are the three known urinary glycoproteins that affect the formation of calcium-containing kidney stones or calculus.
Other endogenous inhibitors include calgranulin (an S-100 calcium-binding protein), Tamm–Horsfall protein, glycosaminoglycans, uropontin (a form of osteopontin), nephrocalcin (an acidic glycoprotein), prothrombin F1 peptide, and bikunin (uronic acid-rich protein).

Medullary cystic kidney disease

Medullary cystic diseasemedullary cystic kidney disease-2Medullary cysts
Defects in this gene are associated with the autosomal dominant renal disorders medullary cystic kidney disease-2 (MCKD2) and familial juvenile hyperuricemic nephropathy (FJHN).
The genes produce the protein mucin-1 and uromodulin, respectively.

Gout

gouty arthritispodagragout attack
These disorders are characterized by juvenile onset of hyperuricemia, gout, and progressive kidney failure.
The rare genetic disorders familial juvenile hyperuricemic nephropathy, medullary cystic kidney disease, phosphoribosylpyrophosphate synthetase superactivity and hypoxanthine-guanine phosphoribosyltransferase deficiency as seen in Lesch-Nyhan syndrome, are complicated by gout.

Frank Horsfall

The glycoprotein was first purified in 1952 by Igor Tamm and Frank Horsfall from the urine of healthy individuals.
The Tamm–Horsfall protein is named after Igor Tamm and him.

Myeloma cast nephropathy

cast nephropathy
This is known as myeloma cast nephropathy.
In myeloma cast nephropathy, filtered κ or λ light chains that bind to Tamm-Horsfall protein precipitate in the renal tubule.

Multiple myeloma

myelomabone-marrow cancerbone marrow cancer
In multiple myeloma, there is often protein cast in the distal convoluted tubule and collecting duct of the kidneys, mainly consisting of immunoglobulin light chain known as Bence Jones protein, but often also contain Tamm–Horsfall protein.
Additional findings may include a raised calcium level (when osteoclasts are breaking down bone, releasing it into the bloodstream), raised serum creatinine level due to reduced kidney function, which is mainly due to casts of paraprotein deposition in the kidney, although the cast may also contain complete immunoglobulins, Tamm-Horsfall protein and albumin.

Glycoprotein

glycoproteinsmembrane glycoproteinprotein
The glycoprotein was first purified in 1952 by Igor Tamm and Frank Horsfall from the urine of healthy individuals. The Tamm–Horsfall glycoprotein (THP), also known as uromodulin, is a glycoprotein that in humans is encoded by the UMOD gene. THP is a GPI-anchored glycoprotein.

Gene

genesnumber of genesgene sequence
The Tamm–Horsfall glycoprotein (THP), also known as uromodulin, is a glycoprotein that in humans is encoded by the UMOD gene.

Urine

urinaryhuman urinepiss
Uromodulin is the most abundant protein excreted in ordinary urine.

Glycosylphosphatidylinositol

glycophosphatidylinositolGPIGPI anchor
THP is a GPI-anchored glycoprotein. Uromodulin excretion in urine follows proteolytic cleavage of the ectodomain of its glycophosphatidylinositol-anchored counterpart that is situated on the luminal cell surface of the loop of Henle.

Blood plasma

plasmaserumblood serum
It is not derived from blood plasma but is produced by the thick ascending limb of the loop of Henle of the mammalian kidney.

Dalton (unit)

kDaDaDalton
While the monomeric molecule has a MW of approximately 85 kDa, it is physiologically present in urine in large aggregates of up to several million Da.

Protein

proteinsproteinaceousstructural proteins
When this protein is concentrated at low pH, it forms a gel.

Karolinska Institute

Karolinska InstitutetCaroline InstituteKarolinska
The crystal structure of UMOD was reported In January 2016 by researchers at Karolinska Institutet, in collaboration with groups at San Raffaele Scientific Institute and European Synchrotron Radiation Facility.

European Synchrotron Radiation Facility

ESRFEuropean Synchrotronthe European Synchrotron Radiation Facility (ESRF)
The crystal structure of UMOD was reported In January 2016 by researchers at Karolinska Institutet, in collaboration with groups at San Raffaele Scientific Institute and European Synchrotron Radiation Facility.

Ectodomain

extracellular domainextracellular domainsmicroenvironments
Uromodulin excretion in urine follows proteolytic cleavage of the ectodomain of its glycophosphatidylinositol-anchored counterpart that is situated on the luminal cell surface of the loop of Henle.

Lumen (anatomy)

lumenluminalintraluminal
Uromodulin excretion in urine follows proteolytic cleavage of the ectodomain of its glycophosphatidylinositol-anchored counterpart that is situated on the luminal cell surface of the loop of Henle.

Loop of Henle

loops of HenleHenle’s loopnephron loop
Uromodulin excretion in urine follows proteolytic cleavage of the ectodomain of its glycophosphatidylinositol-anchored counterpart that is situated on the luminal cell surface of the loop of Henle.

Urinary tract infection

cystitisurinary tract infectionsbladder infection
The excretion of uromodulin in urine may provide defense against urinary tract infections caused by uropathogenic bacteria.

Escherichia coli

E. coliE.coliE-coli
A role in bacterial binding and sequestration is suggested by studies showing that Escherichia coli which express MS (mannose-sensitive) pili or fimbriae (also fimbria, from the Latin word for "fringe") can be trapped by Tamm–Horsfall protein via its mannose-containing side chains.

Pilus

pilitype IV piliType I Pili
A role in bacterial binding and sequestration is suggested by studies showing that Escherichia coli which express MS (mannose-sensitive) pili or fimbriae (also fimbria, from the Latin word for "fringe") can be trapped by Tamm–Horsfall protein via its mannose-containing side chains.

Fimbria (bacteriology)

fimbriaefimbriafimbriae, bacterial
A role in bacterial binding and sequestration is suggested by studies showing that Escherichia coli which express MS (mannose-sensitive) pili or fimbriae (also fimbria, from the Latin word for "fringe") can be trapped by Tamm–Horsfall protein via its mannose-containing side chains.