BioPAX pathway converted from "Cation-coupled Chloride cotransporters" in the Reactome database.

Cation-coupled Chloride cotransporters

This event has been computationally inferred from an event that has been demonstrated in another species.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.<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 cytosol

Na+/Cl- cotransportThis event has been computationally inferred from an event that has been demonstrated in another species.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.<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: 74113

extracellular regionGO0005576

sodium(1+) [ChEBI:29101]

sodium(1+)

Reactomehttp://www.reactome.orgChEBI29101

Reactome DB_ID: 188972

chloride [ChEBI:17996]

chloride

ChEBI17996

Reactome DB_ID: 83910

cytosolGO0005829

Reactome DB_ID: 352022

PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Reactome DB_ID: 10120730

plasma membraneGO0005886

UniProt:A0A287BHP2SLC12A3

Sus scrofa

NCBI Taxonomy9823UniProtA0A287BHP2

Chain Coordinates

EQUAL

1021

EQUAL

GO0015378

GO molecular function

Reactome Database ID Release 7510120731Database 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=10120731Reactome Database ID Release 7510120733Database 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=10120733ReactomeR-SSC-426130

Reactome 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-SSC-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 annotationIEAGOIEA

SLC12A1,2 cotransports Na+, K+, 2Cl- from extracellular region to cytosol

Na+, K+/2Cl- cotransportThis event has been computationally inferred from an event that has been demonstrated in another species.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.<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: 74126

potassium(1+) [ChEBI:29103]

potassium(1+)

K+Potassium

ChEBI29103

Reactome DB_ID: 74113

Reactome DB_ID: 188972

Reactome DB_ID: 83910

Reactome DB_ID: 352022

Reactome DB_ID: 29804

PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Converted from EntitySet in Reactome

Reactome DB_ID: 10120723

SLC12A1,2 [plasma membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntitySLC12A2 [plasma membrane]SLC12A1 [plasma membrane]

UniProtA0A287AEN4UniProtA0A287B828GO0008511

GO molecular function

Reactome Database ID Release 7510120724Database 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=10120724Reactome Database ID Release 7510120726Database 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=10120726ReactomeR-SSC-426086

Reactome 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-SSC-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 annotationIEAGOIEA

SLC12A4,5,6,7 cotransport K+, Cl- from cytosol to extracellular region

K+/Cl- cotransportThis event has been computationally inferred from an event that has been demonstrated in another species.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.<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: 352022

Reactome DB_ID: 29804

Reactome DB_ID: 74126

Reactome DB_ID: 188972

PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Converted from EntitySet in Reactome

Reactome DB_ID: 10120751

SLC12A4,5,6,7 [plasma membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntitySLC12A5 [plasma membrane]SLC12A4 [plasma membrane]SLC12A6 [plasma membrane]SLC12A7 [plasma membrane]

UniProtA0A287BS17UniProtO18887UniProtF2Z5K1UniProtA0A287B5R1GO0015379

GO molecular function

Reactome Database ID Release 7510120752Database 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=10120752Reactome Database ID Release 7510120754Database 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=10120754ReactomeR-SSC-426155

Reactome 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-SSC-426155.1K+/Cl- cotransport is implicated not only in regulatory volume decrease, but also in transepithelial salt absorption, renal K+ secretion, myocardial K+ loss during ischemia and regulation of neuronal Cl- concentration. Four genes (SLC12A4-7) encode the K+/Cl- cotransporters KCC1-4 respectively. Cotransport of K+ and Cl- is electroneutral with a 1:1 stoichiometry. These cotransporters function as homomultimers or heteromultimers with other K+/Cl- cotransporters. SLC12A4 encodes KCC1 (Gillen CM et al, 1996). KCC1 is ubiquitously expressed, suggesting a housekeeping role in the regulation of cell volume. SLC12A5 encodes KCC2 (Song L et al, 2002). KCC2's expression is restricted to neurons in the CNS and retina. It is thought KCC2 is important for Cl- homeostasis in neurons. SLC12A6 encodes KCC3 (Race JE et al, 1999; Mount DB et al, 1999). KCC3 is highly expressed in heart, brain, spinal cord, kidney, muscle, pancreas and placenta. Defects in SLC12A6 are a cause of agenesis of the corpus callosum with peripheral neuropathy (ACCPN) (Howard HC et al, 2002). SLC12A7 encodes KCC4 (Mount DB et al, 1999) which is widely expressed, especially in the kidney. It is thought to play a role in transepithelial transport of Cl- by the proximal tubule.

8663127Pubmed1996Molecular cloning and functional expression of the K-Cl cotransporter from rabbit, rat, and human. A new member of the cation-chloride cotransporter familyGillen, CMBrill, SPayne, JAForbush B, 3rdJ Biol Chem 271:16237-4410347194Pubmed1999Cloning and characterization of KCC3 and KCC4, new members of the cation-chloride cotransporter gene familyMount, DBMercado, ASong, LXu, JGeorge AL, JrDelpire, EGamba, GJ Biol Chem 274:16355-6210600773Pubmed1999Molecular cloning and functional characterization of KCC3, a new K-Cl cotransporterRace, JEMakhlouf, FNLogue, PJWilson, FHDunham, PBHoltzman, EJAm J Physiol 277:C1210-912106695Pubmed2002Molecular, functional, and genomic characterization of human KCC2, the neuronal K-Cl cotransporterSong, LMercado, AVázquez, NXie, QDesai, RGeorge AL, JrGamba, GMount, DBBrain Res Mol Brain Res 103:91-10512368912Pubmed2002The K-Cl cotransporter KCC3 is mutant in a severe peripheral neuropathy associated with agenesis of the corpus callosumHoward, HCMount, DBRochefort, DByun, NDupré, NLu, JFan, XSong, LRivière, JBPrévost, CHorst, JSimonati, ALemcke, BWelch, REngland, RZhan, FQMercado, ASiesser, WBGeorge AL, JrMcDonald, MPBouchard, JPMathieu, JDelpire, ERouleau, Guy ANat Genet 32:384-92inferred by electronic annotationIEAGOIEA

Reactome Database ID Release 7510186303Database 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=10186303ReactomeR-SSC-426117

Reactome 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-SSC-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. 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. 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