UniProt functional annotation for P51795



	UniProt functional annotation for P51795

UniProt code: P51795.

Organism: Homo sapiens (Human).

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

Function: Proton-coupled chloride transporter. Functions as antiport system and exchanges chloride ions against protons. Important for normal acidification of the endosome lumen. May play an important role in renal tubular function.

Subunit: Interacts with NEDD4 and NEDD4L. {ECO:0000269|PubMed:15489223}.

Subcellular location: Golgi apparatus membrane {ECO:0000269|PubMed:19019917}; Multi-pass membrane protein {ECO:0000269|PubMed:19019917}. Endosome membrane {ECO:0000269|PubMed:19019917}; Multi-pass membrane protein {ECO:0000269|PubMed:19019917}. Cell membrane {ECO:0000269|PubMed:19019917}; Multi-pass membrane protein {ECO:0000269|PubMed:19019917}.

Tissue specificity: Kidney. Moderately expressed in aortic vascular smooth muscle and endothelial cells, and at a slightly higher level in the coronary vascular smooth muscle. {ECO:0000269|PubMed:10198195}.

Ptm: Ubiquitinated by NEDD4L in the presence of albumin; which promotes endocytosis and proteasomal degradation. {ECO:0000269|PubMed:15489223}.

Disease: Hypophosphatemic rickets, X-linked recessive (XLRHR) [MIM:300554]: A renal disease belonging to the 'Dent disease complex', a group of disorders characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis, and renal insufficiency. The spectrum of phenotypic features is remarkably similar in the various disorders, except for differences in the severity of bone deformities and renal impairment. XLRH patients present with rickets or osteomalacia, hypophosphatemia due to decreased renal tubular phosphate reabsorption, hypercalciuria, and low molecular weight proteinuria. Patients develop nephrocalcinosis with progressive renal failure in adulthood. Female carriers may have asymptomatic hypercalciuria or hypophosphatemia only. {ECO:0000269|PubMed:21305656, ECO:0000269|PubMed:8559248}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Nephrolithiasis 2 (NPHL2) [MIM:300009]: An X-linked recessive renal disease belonging to the 'Dent disease complex', a group of disorders characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis, and renal insufficiency. The spectrum of phenotypic features is remarkably similar in the various disorders, except for differences in the severity of bone deformities and renal impairment. Nephrolithiasis type 2 patients manifest hypercalciuria, hypophosphatemia, aminoaciduria, nephrocalcinosis and nephrolithiasis, renal insufficiency leading to renal failure in adulthood, rickets (33% of patients) and osteomalacia. {ECO:0000269|PubMed:15086899, ECO:0000269|PubMed:16247550, ECO:0000269|PubMed:16416111, ECO:0000269|PubMed:16822791, ECO:0000269|PubMed:17262170, ECO:0000269|PubMed:18025833, ECO:0000269|PubMed:19019917, ECO:0000269|PubMed:19657328, ECO:0000269|PubMed:21305656, ECO:0000269|PubMed:8559248, ECO:0000269|PubMed:9187673, ECO:0000269|PubMed:9259268, ECO:0000269|PubMed:9602200, ECO:0000269|PubMed:9853249}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Nephrolithiasis 1 (NPHL1) [MIM:310468]: An X-linked recessive renal disease belonging to the 'Dent disease complex', a group of disorders characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis and renal insufficiency. The spectrum of phenotypic features is remarkably similar in the various disorders, except for differences in the severity of bone deformities and renal impairment. Nephrolithiasis type 1 presents with hypercalciuria, nephrocalcinosis, renal stones and renal insufficiency. Patients lack urinary acidification defects, rickets, and osteomalacia. {ECO:0000269|PubMed:8559248}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Low molecular weight proteinuria with hypercalciuria and nephrocalcinosis (LMWPHN) [MIM:308990]: An X-linked renal disease belonging to the 'Dent disease complex', a group of disorders characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis, and renal insufficiency. The spectrum of phenotypic features is remarkably similar in the various disorders, except for differences in the severity of bone deformities and renal impairment. LMWPHN is a slowly progressive disorder. Patients tend to have hypercalciuric nephrocalcinosis without rickets or renal failure. {ECO:0000269|PubMed:11136179, ECO:0000269|PubMed:19019917, ECO:0000269|PubMed:9062355}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons. The absence of conserved gating glutamate residues is typical for family members that function as channels.

Similarity: Belongs to the chloride channel (TC 2.A.49) family. ClC- 5/CLCN5 subfamily. {ECO:0000305}.

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:		Proton-coupled chloride transporter. Functions as antiport system and exchanges chloride ions against protons. Important for normal acidification of the endosome lumen. May play an important role in renal tubular function.


Subunit:		Interacts with NEDD4 and NEDD4L. {ECO:0000269\|PubMed:15489223}.
Subcellular location:		Golgi apparatus membrane {ECO:0000269\|PubMed:19019917}; Multi-pass membrane protein {ECO:0000269\|PubMed:19019917}. Endosome membrane {ECO:0000269\|PubMed:19019917}; Multi-pass membrane protein {ECO:0000269\|PubMed:19019917}. Cell membrane {ECO:0000269\|PubMed:19019917}; Multi-pass membrane protein {ECO:0000269\|PubMed:19019917}.
Tissue specificity:		Kidney. Moderately expressed in aortic vascular smooth muscle and endothelial cells, and at a slightly higher level in the coronary vascular smooth muscle. {ECO:0000269\|PubMed:10198195}.
Ptm:		Ubiquitinated by NEDD4L in the presence of albumin; which promotes endocytosis and proteasomal degradation. {ECO:0000269\|PubMed:15489223}.
Disease:		Hypophosphatemic rickets, X-linked recessive (XLRHR) [MIM:300554]: A renal disease belonging to the 'Dent disease complex', a group of disorders characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis, and renal insufficiency. The spectrum of phenotypic features is remarkably similar in the various disorders, except for differences in the severity of bone deformities and renal impairment. XLRH patients present with rickets or osteomalacia, hypophosphatemia due to decreased renal tubular phosphate reabsorption, hypercalciuria, and low molecular weight proteinuria. Patients develop nephrocalcinosis with progressive renal failure in adulthood. Female carriers may have asymptomatic hypercalciuria or hypophosphatemia only. {ECO:0000269\|PubMed:21305656, ECO:0000269\|PubMed:8559248}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Nephrolithiasis 2 (NPHL2) [MIM:300009]: An X-linked recessive renal disease belonging to the 'Dent disease complex', a group of disorders characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis, and renal insufficiency. The spectrum of phenotypic features is remarkably similar in the various disorders, except for differences in the severity of bone deformities and renal impairment. Nephrolithiasis type 2 patients manifest hypercalciuria, hypophosphatemia, aminoaciduria, nephrocalcinosis and nephrolithiasis, renal insufficiency leading to renal failure in adulthood, rickets (33% of patients) and osteomalacia. {ECO:0000269\|PubMed:15086899, ECO:0000269\|PubMed:16247550, ECO:0000269\|PubMed:16416111, ECO:0000269\|PubMed:16822791, ECO:0000269\|PubMed:17262170, ECO:0000269\|PubMed:18025833, ECO:0000269\|PubMed:19019917, ECO:0000269\|PubMed:19657328, ECO:0000269\|PubMed:21305656, ECO:0000269\|PubMed:8559248, ECO:0000269\|PubMed:9187673, ECO:0000269\|PubMed:9259268, ECO:0000269\|PubMed:9602200, ECO:0000269\|PubMed:9853249}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Nephrolithiasis 1 (NPHL1) [MIM:310468]: An X-linked recessive renal disease belonging to the 'Dent disease complex', a group of disorders characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis and renal insufficiency. The spectrum of phenotypic features is remarkably similar in the various disorders, except for differences in the severity of bone deformities and renal impairment. Nephrolithiasis type 1 presents with hypercalciuria, nephrocalcinosis, renal stones and renal insufficiency. Patients lack urinary acidification defects, rickets, and osteomalacia. {ECO:0000269\|PubMed:8559248}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Low molecular weight proteinuria with hypercalciuria and nephrocalcinosis (LMWPHN) [MIM:308990]: An X-linked renal disease belonging to the 'Dent disease complex', a group of disorders characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis, and renal insufficiency. The spectrum of phenotypic features is remarkably similar in the various disorders, except for differences in the severity of bone deformities and renal impairment. LMWPHN is a slowly progressive disorder. Patients tend to have hypercalciuric nephrocalcinosis without rickets or renal failure. {ECO:0000269\|PubMed:11136179, ECO:0000269\|PubMed:19019917, ECO:0000269\|PubMed:9062355}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons. The absence of conserved gating glutamate residues is typical for family members that function as channels.
Similarity:		Belongs to the chloride channel (TC 2.A.49) family. ClC- 5/CLCN5 subfamily. {ECO:0000305}.