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- 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: 298041cytosolGO0005829potassium(1+) [ChEBI:29103]potassium(1+)K+PotassiumReactomehttp://www.reactome.orgChEBI29103Reactome DB_ID: 3520221chloride [ChEBI:17996]chlorideChEBI17996Reactome DB_ID: 1889721extracellular regionGO0005576Reactome DB_ID: 741261PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 10045566plasma 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 PhysicalEntitySLC12A7 [plasma membrane]SLC12A4 [plasma membrane]SLC12A5 [plasma membrane]Bos taurusNCBI Taxonomy9913UniProtA0A3Q1NIV4UniProtE1BCI8UniProtA0A3S5ZPL9GO0015379GO molecular functionReactome Database ID Release 7510045567Database 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=10045567Reactome Database ID Release 7510045569Database 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=10045569ReactomeR-BTA-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-BTA-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.<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.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 271:16237-4412368912Pubmed2002The 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 32:384-9210347194Pubmed1999Cloning 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 274:16355-6212106695Pubmed2002Molecular, 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 103:91-10510600773Pubmed1999Molecular cloning and functional characterization of KCC3, a new K-Cl cotransporterRace, JEMakhlouf, FNLogue, PJWilson, FHDunham, PBHoltzman, EJAm J Physiol 277:C1210-9inferred by electronic annotationIEAGOIEA