Slc12a1
Domain
The RFXV motif mediates binding with OXSR1/OSR1 and STK39/SPAK.
Function
Renal sodium, potassium and chloride ion cotransporter that mediates the transepithelial NaCl reabsorption in the thick ascending limb and plays an essential role in the urinary concentration and volume regulation. Electrically silent transporter system.
Isoform A
High affinity, high capacity cotransporter for sodium, potassium and chloride ions, with a coupling ratio 1Na(+):1K(+):2Cl(-).
Isoform B
High affinity, low capacity cotransporter for sodium, potassium and chloride ions, with a coupling ratio 1Na(+):1K(+):2Cl(-).
Isoform F
Low affinity, low capacity cotransporter for sodium, potassium and chloride ions, with a coupling ratio 1Na(+):1K(+):2Cl(-).
Post-translational modifications
Phosphorylated at Ser-87, Thr-96 and Thr-101 by OXSR1/OSR1 and STK39/SPAK downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4), promoting its activity (PubMed:21321328). Short-term cyclosporine administration increases SLC12A1 phosphorylation in kidney thick ascending limb, possibly through the inhibition of PPP3CB/calcineurin A beta phosphatase (PubMed:25967121).
Sequence Similarities
Belongs to the SLC12A transporter family.
Tissue Specificity
Predominantly expressed in kidney (at protein level).
Isoform A
Kidney-specific; most highly expressed in the outer stripe of outer medulla (at protein level).
Isoform B
Kidney-specific; most highly expressed in the cortical thick ascending limb (at protein level).
Isoform F
Kidney-specific; most highly expressed in the inner stripe of outer medulla (at protein level).
Cellular localization
- Apical cell membrane
- Multi-pass membrane protein
Alternative names
Nkcc2, Slc12a1, Solute carrier family 12 member 1, Bumetanide-sensitive sodium-(potassium)-chloride cotransporter 1, Kidney-specific Na-K-Cl symporter, Na-K-2Cl cotransporter 2, BSC1, mNKCC2