Function
The Solute carrier family 12 consists of 9 members which encode electroneutral cation-coupled chloride cotransporters. NKCCs play a vial role in the regulation of ionic balance. NKCCs utilize the existing Na+ and K+ gradients to move Cl- into or out of cells[1].
- Solute carrier family 12 member 1 (NKCC 1) is a Na+/K+/Cl- cotransporter playing a major role in concentrating urine and in most of the NaCl resorption.
- Solute carrier family 12 member 2 (NKCC 2) is a Na+/K+/Cl- cotransporter across membranes, involved in chloride transport, metal ion transport and positive regulation of cell volume.
- Solute carrier family 12 member 3 (NKCC 3) is a Na+/Cl- cotransporter playing a major role in most of the NaCl resorption in the tubule of kidneys[2].
- Solute carrier family 12 member 4 (NKCC 4 ) mediates the coupled movement of K+ and Cl- ions across the plasma membrane.
- Solute carrier family 12 member 5 (NKCC 5) is a K+/Cl- cotransporter maintaining Cl homeostasis in neutrons[3].
- Solute carrier family 12 member 6 (NKCC 6) is a K+/Cl- cotransporter activated by swelling of the cell.
Disease
Mutations in NKCC 2 cause neurodevelopmental disorder non-syndromic hearing loss[4]. Mutations in NKCC 3 play pathogenic effects in Gitelman syndrome[5]. Polymorphism in NKCC 3 contribute to genetic susceptibility to diabetic nephropathy and essential hypertension[6]. Mutations in NKCC 6 are associated with severe sensorimotor neuropathy (ACCPN)[7].
Structural highlights
NKCC 2 cotransports Na+, K+, Cl- in the molar ration of 1:1:2. The 3D structure of NKCC 2 complex with these ions show only K+ and one Cl- ion. [8].
3D structures of solute carrier family 12
Solute carrier family 12 3D structures
