ID:S12A3_HUMAN DESCRIPTION: RecName: Full=Solute carrier family 12 member 3; AltName: Full=Na-Cl cotransporter; Short=NCC; AltName: Full=Na-Cl symporter; AltName: Full=Thiazide-sensitive sodium-chloride cotransporter; FUNCTION: Key mediator of sodium and chloride reabsorption in this nephron segment, accounting for a significant fraction of renal sodium reabsorption. ENZYME REGULATION: Activated by WNK3. SUBUNIT: Interacts with KLHL3. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. TISSUE SPECIFICITY: Predominant in kidney. PTM: Ubiquitinated; ubiquitination is essential for regulation of endocytosis (By similarity). May be ubiquitinated by the BCR(KLHL3) complex. DISEASE: Defects in SLC12A3 are the cause of Gitelman syndrome (GS) [MIM:263800]. GS is an autosomal recessive disorder characterized by hypokalemic alkalosis in combination with hypomagnesemia, low urinary calcium, and increased renin activity associated with normal blood pressure. Patients are often asymptomatic or present transient periods of muscular weakness and tetany, usually accompanied by abdominal pain, vomiting and fever. The phenotype is highly heterogeneous in terms of age at onset and severity. Cardinal features such as hypocalciuria and hypomagnesemia might also change during the life cycle of a given patient. GS has overlapping features with Bartter syndrome. MISCELLANEOUS: Target of thiazide diuretics used in the treatment of high blood pressure (PubMed:8528245). SIMILARITY: Belongs to the SLC12A transporter family. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/SLC12A3";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P55017
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006811 ion transport GO:0006814 sodium ion transport GO:0035725 sodium ion transmembrane transport GO:0055085 transmembrane transport GO:1902476 chloride transmembrane transport
AK315298 - Homo sapiens cDNA, FLJ96318. AK223133 - Homo sapiens mRNA, solute carrier family 12 (sodium/chloride transporters), member 3 variant, clone: KDN02262. X91220 - H.sapiens mRNA for Na-Cl electroneutral thiazide-sensitive cotransporter. U44128 - Human thiazide-sensitive Na-Cl cotransporter (hTSC) mRNA, complete cds. AB463268 - Synthetic construct DNA, clone: pF1KB7293, Homo sapiens SLC12A3 gene for solute carrier family 12 (sodium/chloride transporters), member 3, without stop codon, in Flexi system. BC111850 - Synthetic construct Homo sapiens clone IMAGE:40080836, MGC:133390 SLC12A3 protein (SLC12A3) mRNA, encodes complete protein.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein P55017 (Reactome details) participates in the following event(s):
R-HSA-426130 SLC12A3 cotransports Cl-, Na+ from extracellular region to cytosol R-HSA-426117 Cation-coupled Chloride cotransporters R-HSA-425393 Metabolism of nitrogenous molecules R-HSA-425407 SLC-mediated transmembrane transport R-HSA-382551 Transport of small molecules
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
