BioPAX pathway converted from "Cation-coupled Chloride cotransporters" in the Reactome database.Cation-coupled Chloride cotransportersCation-coupled Chloride cotransportersThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>SLC12A3 cotransports Cl-, Na+ from extracellular region to cytosolSLC12A3 cotransports Cl-, Na+ from extracellular region to cytosolNa+/Cl- cotransportThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 741131extracellular regionGO0005576sodium(1+) [ChEBI:29101]sodium(1+)Reactomehttp://www.reactome.orgChEBI29101Reactome DB_ID: 1889721chloride [ChEBI:17996]chlorideChEBI17996Reactome DB_ID: 839101cytosolGO0005829Reactome DB_ID: 3520221PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 10513452plasma membraneGO0005886Homologues of SLC12A3 [plasma membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityNcc69 [plasma membrane]NKCC [plasma membrane]Drosophila melanogasterNCBI Taxonomy7227UniProtM9PI37UniProtQ9VNC7GO0015378GO molecular functionReactome Database ID Release 7510513453Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10513453Reactome Database ID Release 7510513455Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10513455ReactomeR-DME-4261301Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-426130.1The SLC12A3 gene encodes for the Thiazide-sensitive sodium-chloride cotransporter (TSC). TSC mediates sodium and chloride removal from the distal convoluted tubule of the kidney (Mastroianni N et al, 1996). Defects in SLC12A3 are the cause of Gitelman syndrome (GS). GS is an autosomal recessive disorder that allows the kidneys to pass sodium, magnesium, chloride, and potassium into the urine, rather than being reabsorbed into the bloodstream (Simon et al. 1996). This cotransporter is the major target for thiazide-type diuretics, used in the treatment of hypertension, extracellular fluid overload and renal stone disease.8812482Pubmed1996Molecular cloning, expression pattern, and chromosomal localization of the human Na-Cl thiazide-sensitive cotransporter (SLC12A3)Mastroianni, NDe Fusco, MZollo, MArrigo, GZuffardi, OBettinelli, ABallabio, ACasari, GGenomics 35:486-938528245Pubmed1996Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporterSimon, DBNelson-Williams, CBia, MJEllison, DKaret, FEMolina, AMVaara, IIwata, FCushner, HMKoolen, MGainza, FJGitleman, HJLifton, RPNat Genet 12:24-30inferred by electronic annotationIEAGOIEASLC12A1,2 cotransports Na+, K+, 2Cl- from extracellular region to cytosolSLC12A1,2 cotransports Na+, K+, 2Cl- from extracellular region to cytosolNa+, K+/2Cl- cotransportThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 741261potassium(1+) [ChEBI:29103]potassium(1+)K+PotassiumChEBI29103Reactome DB_ID: 741131Reactome DB_ID: 1889722Reactome DB_ID: 839101Reactome DB_ID: 3520222Reactome DB_ID: 298041PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 10513443SLC12A1,2 [plasma membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityNcc69 [plasma membrane]Ncc69 [plasma membrane]NKCC [plasma membrane]GO0008511GO molecular functionReactome Database ID Release 7510513444Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10513444Reactome Database ID Release 7510513446Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10513446ReactomeR-DME-4260861Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-426086.1Two genes (SLC12A1 and SLC12A2) encode Na+,K+/2Cl- cotransporters (NKCC2 and NKCC1 respectively). SLC12A1 (Simon DB et al, 1996) is kidney-specific whilst SLC12A2 (Payne JA et al, 1995) is ubiquitously expressed. Two Cl- ions are electroneutrally transported into cells with a Na+ ion and a K+ ion.7629105Pubmed1995Primary structure, functional expression, and chromosomal localization of the bumetanide-sensitive Na-K-Cl cotransporter in human colonPayne, JAXu, JCHaas, MLytle, CYWard, DForbush B, 3rdJ Biol Chem 270:17977-858640224Pubmed1996Bartter's syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na-K-2Cl cotransporter NKCC2Simon, DBKaret, FEHamdan, JMDiPietro, ASanjad, SALifton, RPNat Genet 13:183-8inferred by electronic annotationIEAGOIEAReactome Database ID Release 7510568649Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10568649ReactomeR-DME-4261171Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DME-426117.1The cation-chloride cotransporter family (SLC12 gene family) are membrane proteins that cotranslocate chloride (Cl-) with either Na+, K+, or both cations electroneutrally. The general topology of these proteins feature 12 transmembrane domains flanked by hydrophilic NH2 and COOH-terminal domains. They are secondary transporters and movement of these cations is determined by gradients established by primary transporters such as Na+-K+-ATPase. Cotransporters that use Na+ as the driving force move Cl- into the cell because Na+ concentration is higher in the extracellular region. Conversely, cotransporters that use K+ as the driving force move Cl- out of the cell because K+ concentration is higher inside the cell.<br><br>The SLC12 gene family contains nine members, of which seven are clearly characterized genes and two are orphans. They encode cotransporter proteins which are 1) involved in Cl- homeostasis, 2) regulate cell volume, 3) involved in transepithelial ion movement (salt reabsorption in the kidney) and 4) involved in response to neurotransmitters such as GABA. <br><br>Three different cotransporter subtypes are expressed by the seven characterized genes; one thiazide-sensitive Na+/Cl- cotransporter, two loop diuretic-sensitive Na+, K+/2Cl- cotransporters and four K+/Cl- cotransporters (Gamba G, 2005; Hebert SC et al, 2004).15788703Pubmed2005Molecular physiology and pathophysiology of electroneutral cation-chloride cotransportersGamba, GPhysiol Rev 85:423-9312739168Pubmed2004Molecular physiology of cation-coupled Cl- cotransport: the SLC12 familyHebert, SCMount, DBGamba, GPflugers Arch 447:580-93inferred by electronic annotationIEAGOIEA