UniProt functional annotation for P07911



	UniProt functional annotation for P07911

UniProt code: P07911.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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 that may play a role in the water barrier permeability (Probable). May serve as a receptor for binding and endocytosis of cytokines (IL-1, IL-2) and TNF (PubMed:3498215). Facilitates neutrophil migration across renal epithelia (PubMed:20798515). {ECO:0000269|PubMed:20798515, ECO:0000269|PubMed:3498215, ECO:0000305}.

Function: [Uromodulin, secreted form]: In the urine, may contribute to colloid osmotic pressure, retards passage of positively charged electrolytes, prevents urinary tract infection and inhibits formation of liquid containing supersaturated salts and subsequent formation of salt crystals. {ECO:0000250|UniProtKB:Q91X17, ECO:0000305}.

Subunit: [Uromodulin, secreted form]: Homodimer that then polymerizes into long filaments (PubMed:19005207, PubMed:26673890, PubMed:26811476, PubMed:32815518, PubMed:33196145). The filaments can additionally assemble laterally to form a sheet (PubMed:33196145). {ECO:0000269|PubMed:19005207, ECO:0000269|PubMed:26673890, ECO:0000269|PubMed:26811476, ECO:0000269|PubMed:32815518, ECO:0000269|PubMed:33196145}.

Subcellular location: Apical cell membrane {ECO:0000269|PubMed:22776760, ECO:0000269|PubMed:23988501, ECO:0000269|PubMed:26673890, ECO:0000269|PubMed:7028707}; Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:2249987}. Basolateral cell membrane {ECO:0000269|PubMed:7028707}; Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:2249987}. Cell projection, cilium membrane {ECO:0000269|PubMed:20172860}. Note=Only a small fraction sorts to the basolateral pole of tubular epithelial cells compared to apical localization (PubMed:22776760). Secreted into urine after cleavage (PubMed:18375198, PubMed:26811476). Colocalizes with NPHP1 and KIF3A (PubMed:20172860). {ECO:0000269|PubMed:18375198, ECO:0000269|PubMed:20172860, ECO:0000269|PubMed:26811476, ECO:0000269|PubMed:3453112, ECO:0000269|PubMed:7028707}.

Subcellular location: [Uromodulin, secreted form]: Secreted {ECO:0000269|PubMed:18375198, ECO:0000269|PubMed:19005207, ECO:0000269|PubMed:26673890, ECO:0000269|PubMed:26811476, ECO:0000269|PubMed:3453112, ECO:0000269|PubMed:7028707}. Note=Detected in urine. {ECO:0000269|PubMed:18375198, ECO:0000269|PubMed:26811476, ECO:0000269|PubMed:3453112, ECO:0000269|PubMed:7028707}.

Tissue specificity: Expressed in the tubular cells of the kidney. Most abundant protein in normal urine (at protein level). 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. {ECO:0000269|PubMed:18375198, ECO:0000269|PubMed:22776760, ECO:0000269|PubMed:23988501, ECO:0000269|PubMed:3453112, ECO:0000269|PubMed:7028707}.

Domain: The ZP domain mediates polymerization, leading to the formation of long filaments. The core of the filament consists of stacked ZP domains which assemble into a helical structure. Each ZP domain consists of an N-terminal (ZP-N) and C-terminal (ZP-C) region connected by a flexible linker; the linker allows the ZP domain to wrap around the ZP-C subdomain of the preceding subunit. The heavily glycosylated N-terminal part of the protein (containing several EGF-like domains) forms branches which protrude from the core and may be involved in pathogen capture. {ECO:0000269|PubMed:26811476, ECO:0000269|PubMed:32815518, ECO:0000269|PubMed:33196145}.

Ptm: N-glycosylated (PubMed:19005207, PubMed:26673890, PubMed:26811476, PubMed:32815518, PubMed:33196145). 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) (PubMed:22171320). {ECO:0000269|PubMed:19005207, ECO:0000269|PubMed:22171320, ECO:0000269|PubMed:26673890, ECO:0000269|PubMed:26811476, ECO:0000269|PubMed:32815518, ECO:0000269|PubMed:33196145}.

Ptm: Proteolytically cleaved at a conserved C-terminal proteolytic cleavage site to generate the secreted form found in urine (PubMed:18375198, PubMed:19005207). This cleavage is catalyzed by HPN (PubMed:26673890). {ECO:0000269|PubMed:18375198, ECO:0000269|PubMed:19005207, ECO:0000269|PubMed:26673890}.

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. {ECO:0000269|PubMed:12471200, ECO:0000269|PubMed:12629136, ECO:0000269|PubMed:12900848, ECO:0000269|PubMed:14569098, ECO:0000269|PubMed:14570709, ECO:0000269|PubMed:15086896, ECO:0000269|PubMed:15575003, ECO:0000269|PubMed:15983957, ECO:0000269|PubMed:17010121, ECO:0000269|PubMed:21060763, ECO:0000269|PubMed:22776760, ECO:0000269|PubMed:23197950, ECO:0000269|PubMed:23988501, ECO:0000269|PubMed:25436415}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Medullary 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. {ECO:0000269|PubMed:12471200, ECO:0000269|PubMed:14531790, ECO:0000269|PubMed:14570709, ECO:0000269|PubMed:17010121, ECO:0000269|PubMed:25436415, ECO:0000269|PubMed:27729211}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Glomerulocystic 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. {ECO:0000269|PubMed:14570709, ECO:0000269|PubMed:17010121}. Note=The disease is caused by variants affecting the gene represented in this entry.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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 that may play a role in the water barrier permeability (Probable). May serve as a receptor for binding and endocytosis of cytokines (IL-1, IL-2) and TNF (PubMed:3498215). Facilitates neutrophil migration across renal epithelia (PubMed:20798515). {ECO:0000269\|PubMed:20798515, ECO:0000269\|PubMed:3498215, ECO:0000305}.



Function:		[Uromodulin, secreted form]: In the urine, may contribute to colloid osmotic pressure, retards passage of positively charged electrolytes, prevents urinary tract infection and inhibits formation of liquid containing supersaturated salts and subsequent formation of salt crystals. {ECO:0000250\|UniProtKB:Q91X17, ECO:0000305}.


Subunit:		[Uromodulin, secreted form]: Homodimer that then polymerizes into long filaments (PubMed:19005207, PubMed:26673890, PubMed:26811476, PubMed:32815518, PubMed:33196145). The filaments can additionally assemble laterally to form a sheet (PubMed:33196145). {ECO:0000269\|PubMed:19005207, ECO:0000269\|PubMed:26673890, ECO:0000269\|PubMed:26811476, ECO:0000269\|PubMed:32815518, ECO:0000269\|PubMed:33196145}.
Subcellular location:		Apical cell membrane {ECO:0000269\|PubMed:22776760, ECO:0000269\|PubMed:23988501, ECO:0000269\|PubMed:26673890, ECO:0000269\|PubMed:7028707}; Lipid-anchor, GPI-anchor {ECO:0000269\|PubMed:2249987}. Basolateral cell membrane {ECO:0000269\|PubMed:7028707}; Lipid-anchor, GPI-anchor {ECO:0000269\|PubMed:2249987}. Cell projection, cilium membrane {ECO:0000269\|PubMed:20172860}. Note=Only a small fraction sorts to the basolateral pole of tubular epithelial cells compared to apical localization (PubMed:22776760). Secreted into urine after cleavage (PubMed:18375198, PubMed:26811476). Colocalizes with NPHP1 and KIF3A (PubMed:20172860). {ECO:0000269\|PubMed:18375198, ECO:0000269\|PubMed:20172860, ECO:0000269\|PubMed:26811476, ECO:0000269\|PubMed:3453112, ECO:0000269\|PubMed:7028707}.
Subcellular location:		[Uromodulin, secreted form]: Secreted {ECO:0000269\|PubMed:18375198, ECO:0000269\|PubMed:19005207, ECO:0000269\|PubMed:26673890, ECO:0000269\|PubMed:26811476, ECO:0000269\|PubMed:3453112, ECO:0000269\|PubMed:7028707}. Note=Detected in urine. {ECO:0000269\|PubMed:18375198, ECO:0000269\|PubMed:26811476, ECO:0000269\|PubMed:3453112, ECO:0000269\|PubMed:7028707}.
Tissue specificity:		Expressed in the tubular cells of the kidney. Most abundant protein in normal urine (at protein level). 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. {ECO:0000269\|PubMed:18375198, ECO:0000269\|PubMed:22776760, ECO:0000269\|PubMed:23988501, ECO:0000269\|PubMed:3453112, ECO:0000269\|PubMed:7028707}.
Domain:		The ZP domain mediates polymerization, leading to the formation of long filaments. The core of the filament consists of stacked ZP domains which assemble into a helical structure. Each ZP domain consists of an N-terminal (ZP-N) and C-terminal (ZP-C) region connected by a flexible linker; the linker allows the ZP domain to wrap around the ZP-C subdomain of the preceding subunit. The heavily glycosylated N-terminal part of the protein (containing several EGF-like domains) forms branches which protrude from the core and may be involved in pathogen capture. {ECO:0000269\|PubMed:26811476, ECO:0000269\|PubMed:32815518, ECO:0000269\|PubMed:33196145}.
Ptm:		N-glycosylated (PubMed:19005207, PubMed:26673890, PubMed:26811476, PubMed:32815518, PubMed:33196145). 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) (PubMed:22171320). {ECO:0000269\|PubMed:19005207, ECO:0000269\|PubMed:22171320, ECO:0000269\|PubMed:26673890, ECO:0000269\|PubMed:26811476, ECO:0000269\|PubMed:32815518, ECO:0000269\|PubMed:33196145}.
Ptm:		Proteolytically cleaved at a conserved C-terminal proteolytic cleavage site to generate the secreted form found in urine (PubMed:18375198, PubMed:19005207). This cleavage is catalyzed by HPN (PubMed:26673890). {ECO:0000269\|PubMed:18375198, ECO:0000269\|PubMed:19005207, ECO:0000269\|PubMed:26673890}.
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. {ECO:0000269\|PubMed:12471200, ECO:0000269\|PubMed:12629136, ECO:0000269\|PubMed:12900848, ECO:0000269\|PubMed:14569098, ECO:0000269\|PubMed:14570709, ECO:0000269\|PubMed:15086896, ECO:0000269\|PubMed:15575003, ECO:0000269\|PubMed:15983957, ECO:0000269\|PubMed:17010121, ECO:0000269\|PubMed:21060763, ECO:0000269\|PubMed:22776760, ECO:0000269\|PubMed:23197950, ECO:0000269\|PubMed:23988501, ECO:0000269\|PubMed:25436415}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Medullary 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. {ECO:0000269\|PubMed:12471200, ECO:0000269\|PubMed:14531790, ECO:0000269\|PubMed:14570709, ECO:0000269\|PubMed:17010121, ECO:0000269\|PubMed:25436415, ECO:0000269\|PubMed:27729211}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Glomerulocystic 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. {ECO:0000269\|PubMed:14570709, ECO:0000269\|PubMed:17010121}. Note=The disease is caused by variants affecting the gene represented in this entry.