K/Cl co-transporter 1 (IPR000622)

Short name: KCC1

Overlapping homologous superfamilies


Family relationships


The K-Cl co-transporter (KCC) mediates the coupled movement of K+ and Cl- ions across the plasma membrane of many animal cells. This transport is involved in the regulatory volume decrease in response to cell swelling in red blood cells, and has 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].

Four isoforms of KCC have been identified: KCC1, KCC2, KCC3, and KCC4. They are predicted to have 12 transmembrane (TM) regions in a central hydrophobic domain, together with hydrophilic N- and C-termini that are likely cytoplasmic. Comparison of their sequences with those of other ion-tranporting 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 and KCC3 are widely expressed in human tissues, while KCC2 is are 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, PMID: 10600773].

KCC1, also known as solute carrier family 12 member 4 (SLC12A4), is widely expressed in human tissues, and when heterologously expressed, possesses the functional characteristics of the well-studied red blood cell K-Cl co-transporter, including stimulation by both swelling and N-ethylmaleimide. Several splice variants have also been identified.

GO terms

Biological Process

GO:0006811 ion transport

Molecular Function

GO:0005215 transporter activity

Cellular Component

GO:0016020 membrane

Contributing signatures

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