SLC12A6
Domain
Isoform 2
N-terminal loop binds to the intracellular vestibule of the transporter, arresting the transporter in an inhibited state.
Function
Isoform 1
Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:10600773, PubMed:11551954, PubMed:16048901, PubMed:18566107, PubMed:19665974, PubMed:21628467, PubMed:27485015). May contribute to cell volume homeostasis in single cells (PubMed:16048901, PubMed:27485015).
Isoform 2
Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901, PubMed:33199848, PubMed:34031912). May contribute to cell volume homeostasis in single cells (Probable).
Isoform 3
Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901). May contribute to cell volume homeostasis in single cells (Probable).
Isoform 4
Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901). May contribute to cell volume homeostasis in single cells (Probable).
Isoform 5
Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901). May contribute to cell volume homeostasis in single cells (Probable).
Isoform 6
Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901). May contribute to cell volume homeostasis in single cells (Probable).
Involvement in disease
Agenesis of the corpus callosum, with peripheral neuropathy
ACCPN
A disease that is characterized by severe progressive sensorimotor neuropathy, intellectual disability, dysmorphic features and complete or partial agenesis of the corpus callosum.
None
The disease is caused by variants affecting the gene represented in this entry.
Charcot-Marie-Tooth disease, axonal, 2II
CMT2II
A dominant axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylated, phosphorylation regulates transporter activity (PubMed:19665974, PubMed:21613606, PubMed:34031912). Phosphorylated at Thr-991 and Thr-1048 by OXSR1/OSR1 and STK39/SPAK downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4), inhibiting the potassium-chloride cotransport activity (PubMed:19665974, PubMed:21613606).
N-glycosylated.
Sequence Similarities
Belongs to the SLC12A transporter family. K/Cl co-transporter subfamily.
Tissue Specificity
Expressed in brain (at protein level) (PubMed:21628467). Highly expressed in heart, brain and kidney. Detected at lower levels in skeletal muscle, placenta, lung and pancreas (PubMed:10600773). Detected in umbilical vein endothelial cells (PubMed:16048901).
Isoform 2
More abundant in kidney.
Isoform 5
Testis specific.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
- Basolateral cell membrane
- Multi-pass membrane protein
Alternative names
KCC3, SLC12A6, Solute carrier family 12 member 6, Electroneutral potassium-chloride cotransporter 3, K-Cl cotransporter 3