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

Stable Identifier
Reaction [transition]
Homo sapiens
K+/Cl- cotransport
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K+/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.

Literature References
PubMed ID Title Journal Year
10347194 Cloning and characterization of KCC3 and KCC4, new members of the cation-chloride cotransporter gene family

Mount, DB, Mercado, A, Song, L, Xu, J, George AL, Jr, Delpire, E, Gamba, G

J Biol Chem 1999
8663127 Molecular cloning and functional expression of the K-Cl cotransporter from rabbit, rat, and human. A new member of the cation-chloride cotransporter family

Gillen, CM, Brill, S, Payne, JA, Forbush B, 3rd

J Biol Chem 1996
12106695 Molecular, functional, and genomic characterization of human KCC2, the neuronal K-Cl cotransporter

Song, L, Mercado, A, Vázquez, N, Xie, Q, Desai, R, George AL, Jr, Gamba, G, Mount, DB

Brain Res Mol Brain Res 2002
10600773 Molecular cloning and functional characterization of KCC3, a new K-Cl cotransporter

Race, JE, Makhlouf, FN, Logue, PJ, Wilson, FH, Dunham, PB, Holtzman, EJ

Am J Physiol 1999
12368912 The K-Cl cotransporter KCC3 is mutant in a severe peripheral neuropathy associated with agenesis of the corpus callosum

Howard, HC, Mount, DB, Rochefort, D, Byun, N, Dupré, N, Lu, J, Fan, X, Song, L, Rivière, JB, Prévost, C, Horst, J, Simonati, A, Lemcke, B, Welch, R, England, R, Zhan, FQ, Mercado, A, Siesser, WB, George AL, Jr, McDonald, MP, Bouchard, JP, Mathieu, J, Delpire, E, Rouleau, GA

Nat Genet 2002
Participant Of
Catalyst Activity
Catalyst Activity
potassium:chloride symporter activity of SLC12A4,5,6,7 [plasma membrane]
Physical Entity
Orthologous Events
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