BioPAX pathway converted from "SLC12A4,5,6,7 cotransport K+, Cl- from cytosol to extracellular region" in the Reactome database.SLC12A4,5,6,7 cotransport K+, Cl- from cytosol to extracellular regionSLC12A4,5,6,7 cotransport K+, Cl- from cytosol to extracellular regionK+/Cl- cotransportK+/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.<br>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.Authored: Jassal, Bijay, 2009-06-12Reviewed: He, L, 2009-08-24Edited: Jassal, Bijay, 2009-06-12Reactome DB_ID: 3520221cytosolGO0005829chloride [ChEBI:17996]chlorideReactomehttp://www.reactome.orgChEBI17996Reactome DB_ID: 298041potassium(1+) [ChEBI:29103]potassium(1+)K+PotassiumChEBI29103Reactome DB_ID: 741261extracellular regionGO0005576Reactome DB_ID: 1889721PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 426109plasma membraneGO0005886SLC12A4,5,6,7 [plasma membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntitySLC12A4 [plasma membrane]SLC12A5 [plasma membrane]SLC12A6 [plasma membrane]SLC12A7 [plasma membrane]Homo sapiensNCBI Taxonomy9606UniProtQ9UP95UniProtQ9H2X9UniProtQ9UHW9UniProtQ9Y666GO0015379GO molecular functionReactome Database ID Release 75426138Database 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=426138Reactome Database ID Release 75426155Database 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=426155ReactomeR-HSA-4261551Reactome 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-HSA-426155.18663127Pubmed1996Molecular 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 32:384-92