K/Cl co-transporter (IPR000076)

Short name: KCL_cotranspt

Overlapping homologous superfamilies


Family relationships


K+Cl- cotransporters (KCCs) belong to the SLC12 family and act as electroneutral symporters of K+ and Cl- ions across the plasma membrane [PMID: 6929518, PMID: 11125215]. They are major determinants of osmotic homeostasis. They are involved in the regulatory volume decrease in response to cell swelling in red blood cells, and have been proposed to play a role in the vectorial movement of Cl- across kidney epithelia. The transport process involves one for one electroneutral movement of K+ together with Cl-, and, in all known mammalian cells, the net movement is outward [PMID: 8663127].

In neurones, it appears to play a unique role in maintaining low intracellular Cl-concentration, which is required for the functioning of Cl- dependent fast synaptic inhibition, mediated by certain neurotransmitters, such as gamma-aminobutyric acid (GABA) and glycine.

Four isoforms of KCC have been identified: KCC1, KCC2, KCC3, and KCC4. The four KCC isoforms share a common protein structure with a central core of twelve hydrophobic transmembrane domains [PMID: 10347194]. Comparison of their sequences with those of other ion-transporting membrane proteins reveals that they are part of a new superfamily of cation-chloride co-transporters, which includes the Na-Cl and Na-K-2Cl co-transporters. KCC1 is widely expressed in human tissues, while KCC2 is expressed only in brain neurones, making it likely that this is the isoform responsible for maintaining low Cl- concentration in neurones [PMID: 8663311, PMID: 9930699].

GO terms

Biological Process

GO:0006811 ion transport

Molecular Function

GO:0015379 potassium:chloride symporter activity

Cellular Component

GO:0016021 integral component of membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.