K/Cl co-transporter 2 (IPR030358)

Short name: KCC2

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. 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].

KCC2, also known as solute carrier family 12 member 5 (SLC12A5), mediates electroneutral potassium-chloride cotransport in mature neurons. It is required for maintaining low intracellular Cl-, which is essential for fast inhibitory synaptic transmission, mediated by certain neurotransmitters, such as gamma-aminobutyric acid (GABA) and glycine [PMID: 19323993, PMID: 22723714, PMID: 9930699]. KCC2 is regulated in a Ca2+-dependent manner by physiological levels of neuronal activity, playing a key role in the balance between inhibition and excitation [PMID: 12948447]. Aberrant KCC2 regulation results in increased neuronal Cl- and contributes toward the pathology of numerous neurological disorders, including epilepsy and autism [PMID: 18769373].

GO terms

Biological Process

GO:0007268 chemical synaptic transmission
GO:1902476 chloride transmembrane transport
GO:0006811 ion transport

Molecular Function

GO:0015379 potassium:chloride symporter activity

Cellular Component

GO:0005887 integral component of plasma membrane

Contributing signatures

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