SLC12A6
entrez
9990
canonical
uniprot
Q9UHW9
canonical
ensembl
ENSG00000140199
resolver
ensp
ENSP00000290209
resolver
ensp
ENSP00000346112
resolver
ensp
ENSP00000380814
resolver
ensp
ENSP00000380819
resolver
ensp
ENSP00000387725
resolver
ensp
ENSP00000452705
resolver
ensp
ENSP00000452776
resolver
ensp
ENSP00000454168
resolver
genesymbol
SLC12A6
resolver
genesymbol_syn
KCC3
resolver
hgnc
HGNC:10914
resolver
uniprot
A0AV76
resolver
uniprot
Q2VI00
resolver
uniprot
Q6NSI7
resolver
uniprot
Q7Z2E7
resolver
uniprot
Q7Z4G5
resolver
uniprot
Q8TDD4
resolver
uniprot
Q9UFR2
resolver
uniprot
Q9Y642
resolver
uniprot
Q9Y665
resolver
uniprot_entry
Q6NSI7_HUMAN
resolver
uniprot_entry
S12A6_HUMAN
resolver
uniprot_sec
A0AV76
resolver
uniprot_sec
Q2VI00
resolver
uniprot_sec
Q7Z2E7
resolver
uniprot_sec
Q7Z4G5
resolver
uniprot_sec
Q8TDD4
resolver
uniprot_sec
Q9UFR2
resolver
uniprot_sec
Q9Y642
resolver
uniprot_sec
Q9Y665
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited following phosphorylation by OXSR1/OSR1 and STK39/SPAK: phosphorylation takes place downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4) in response to hyperosmotic stress and subsequent cell shrinkage (PubMed:19665974, PubMed:21613606). Activated by N-ethylmaleimide (NEM) (PubMed:10600773). Inhibited by DIOA, bumetanide and furosemide (PubMed:10600773). {ECO:0000269|PubMed:10600773, ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:21613606}.
uniprot
proteins
amino_acid_sequence
MHPPETTTKMASVRFMVTPTKIDDIPGLSDTSPDLSSRSSSRVRFSSRESVPETSRSEPMSEMSGATTSLATVALDPPSDRTSHPQDVIEDLSQNSITGEHSQLLDDGHKKARNAYLNNSNYEEGDEYFDKNLALFEEEMDTRPKVSSLLNRMANYTNLTQGAKEHEEAENITEGKKKPTKTPQMGTFMGVYLPCLQNIFGVILFLRLTWVVGTAGVLQAFAIVLICCCCTMLTAISMSAIATNGVVPAGGSYFMISRALGPEFGGAVGLCFYLGTTFAAAMYILGAIEIFLVYIVPRAAIFHSDDALKESAAMLNNMRVYGTAFLVLMVLVVFIGVRYVNKFASLFLACVIVSILAIYAGAIKSSFAPPHFPVCMLGNRTLSSRHIDVCSKTKEINNMTVPSKLWGFFCNSSQFFNATCDEYFVHNNVTSIQGIPGLASGIITENLWSNYLPKGEIIEKPSAKSSDVLGSLNHEYVLVDITTSFTLLVGIFFPSVTGIMAGSNRSGDLKDAQKSIPIGTILAILTTSFVYLSNVVLFGACIEGVVLRDKFGDAVKGNLVVGTLSWPSPWVIVIGSFFSTCGAGLQSLTGAPRLLQAIAKDNIIPFLRVFGHSKANGEPTWALLLTAAIAELGILIASLDLVAPILSMFFLMCYLFVNLACALQTLLRTPNWRPRFRYYHWALSFMGMSICLALMFISSWYYAIVAMVIAGMIYKYIEYQGAEKEWGDGIRGLSLSAARFALLRLEEGPPHTKNWRPQLLVLLKLDEDLHVKHPRLLTFASQLKAGKGLTIVGSVIVGNFLENYGEALAAEQTIKHLMEAEKVKGFCQLVVAAKLREGISHLIQSCGLGGMKHNTVVMGWPNGWRQSEDARAWKTFIGTVRVTTAAHLALLVAKNISFFPSNVEQFSEGNIDVWWIVHDGGMLMLLPFLLKQHKVWRKCSIRIFTVAQLEDNSIQMKKDLATFLYHLRIEAEVEVVEMHDSDISAYTYERTLMMEQRSQMLRHMRLSKTERDREAQLVKDRNSMLRLTSIGSDEDEETETYQEKVHMTWTKDKYMASRGQKAKSMEGFQDLLNMRPDQSNVRRMHTAVKLNEVIVNKSHEAKLVLLNMPGPPRNPEGDENYMEFLEVLTEGLERVLLVRGGGSEVITIYS
uniprot
proteins
disease_involvement
DISEASE: Agenesis of the corpus callosum, with peripheral neuropathy (ACCPN) [MIM:218000]: A disease that is characterized by severe progressive sensorimotor neuropathy, intellectual disability, dysmorphic features and complete or partial agenesis of the corpus callosum. {ECO:0000269|PubMed:12368912, ECO:0000269|PubMed:16606917, ECO:0000269|PubMed:17893295, ECO:0000269|PubMed:18566107, ECO:0000269|PubMed:21628467}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Charcot-Marie-Tooth disease, axonal, type 2II (CMT2II) [MIM:620068]: 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. {ECO:0000269|PubMed:27485015, ECO:0000269|PubMed:31439721, ECO:0000269|PubMed:35733399}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
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). {ECO:0000269|PubMed:10600773, ECO:0000269|PubMed:11551954, ECO:0000269|PubMed:16048901, ECO:0000269|PubMed:18566107, ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:21628467, ECO:0000269|PubMed:27485015, ECO:0000305|PubMed:16048901}.; FUNCTION: [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). {ECO:0000269|PubMed:16048901, ECO:0000269|PubMed:33199848, ECO:0000269|PubMed:34031912, ECO:0000305|PubMed:16048901}.; FUNCTION: [Isoform 3]: Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901). May contribute to cell volume homeostasis in single cells (Probable). {ECO:0000269|PubMed:16048901, ECO:0000305|PubMed:16048901}.; FUNCTION: [Isoform 4]: Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901). May contribute to cell volume homeostasis in single cells (Probable). {ECO:0000269|PubMed:16048901, ECO:0000305|PubMed:16048901}.; FUNCTION: [Isoform 5]: Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901). May contribute to cell volume homeostasis in single cells (Probable). {ECO:0000269|PubMed:16048901, ECO:0000305|PubMed:16048901}.; FUNCTION: [Isoform 6]: Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901). May contribute to cell volume homeostasis in single cells (Probable). {ECO:0000269|PubMed:16048901, ECO:0000305|PubMed:16048901}.
uniprot
proteins
mass_dalton
127617
uniprot
proteins
mutagenesis
MUTAGEN 96; /note="S->A: Increases Rb(+) uptake; when associated with D-991 and D-991."; /evidence="ECO:0000269|PubMed:34031912"; MUTAGEN 96; /note="S->D: Decreases Rb(+) uptake; when associated with D-991 and D-1048."; /evidence="ECO:0000269|PubMed:34031912"; MUTAGEN 505; /note="R->A: Decrease in Cl(-) efflux."; /evidence="ECO:0000269|PubMed:35759661"; MUTAGEN 586; /note="Q->A: Decrease in Cl(-) efflux."; /evidence="ECO:0000269|PubMed:35759661"; MUTAGEN 668; /note="R->G: Increases transporter activity."; /evidence="ECO:0000269|PubMed:33199848"; MUTAGEN 715; /note="K->R: No effect on transporter activity."; /evidence="ECO:0000269|PubMed:33199848"; MUTAGEN 746; /note="E->A: Slightly reduces transporter activity."; /evidence="ECO:0000269|PubMed:33199848"; MUTAGEN 991; /note="T->A: Decreased phosphorylation by WNK kinases, leading to increased potassium-chloride cotransport activity. Increases Rb(+) uptake; when associated with D-96 and D-1048."; /evidence="ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:34031912"; MUTAGEN 991; /note="T->D: Decreases Rb(+) uptake; when associated with D-96 and D-1048."; /evidence="ECO:0000269|PubMed:34031912"; MUTAGEN 1032; /note="S->A: Does not affect potassium-chloride cotransport activity."; /evidence="ECO:0000269|PubMed:19665974"; MUTAGEN 1048; /note="T->A: Decreased phosphorylation by WNK kinases, leading to increased potassium-chloride cotransport activity. Increases Rb(+) uptake; when associated with D-96 and D-991."; /evidence="ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:34031912"; MUTAGEN 1048; /note="T->D: Decreases Rb(+) uptake; when associated with D-96 and D-991."; /evidence="ECO:0000269|PubMed:34031912
uniprot
proteins
post_translational_modification
PTM: 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). {ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:21613606, ECO:0000269|PubMed:34031912}.; PTM: N-glycosylated. {ECO:0000269|PubMed:10187864, ECO:0000269|PubMed:12368912}.
uniprot
proteins
protein_family
K/Cl co-transporter subfamily
uniprot
proteins
protein_family
SLC12A transporter family
uniprot
proteins
pubmed
10187864
uniprot
proteins
pubmed
10347194
uniprot
proteins
pubmed
10600773
uniprot
proteins
pubmed
11551954
uniprot
proteins
pubmed
12368912
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16048901
uniprot
proteins
pubmed
16572171
uniprot
proteins
pubmed
16606917
uniprot
proteins
pubmed
17893295
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18566107
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19665974
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21613606
uniprot
proteins
pubmed
21628467
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
27485015
uniprot
proteins
pubmed
31439721
uniprot
proteins
pubmed
33199848
uniprot
proteins
pubmed
33310850
uniprot
proteins
pubmed
34031912
uniprot
proteins
pubmed
34267353
uniprot
proteins
pubmed
35733399
uniprot
proteins
pubmed
35759661
uniprot
proteins
sequence_length
1150
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12368912, ECO:0000269|PubMed:17893295, ECO:0000269|PubMed:18566107, ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:21628467}; Multi-pass membrane protein {ECO:0000255}. Basolateral cell membrane {ECO:0000250|UniProtKB:Q924N4}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q924N4}.
uniprot
proteins
transmembrane_region
TRANSMEM 136..158; /note="Discontinuously helical; Name=1"; /evidence="ECO:0000269|PubMed:33199848, ECO:0007744|PDB:6M1Y"; TRANSMEM 166..188; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:33199848, ECO:0007744|PDB:6M1Y"; TRANSMEM 212..245; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:33199848, ECO:0007744|PDB:6M1Y"; TRANSMEM 264..287; /note="Helical; Name=4"; /evidence="ECO:0000269|PubMed:33199848, ECO:0007744|PDB:6M1Y"; TRANSMEM 288..316; /note="Helical; Name=5"; /evidence="ECO:0000269|PubMed:33199848, ECO:0007744|PDB:6M1Y"; TRANSMEM 434..454; /note="Helical; Name=6"; /evidence="ECO:0000269|PubMed:33199848, ECO:0007744|PDB:6M1Y"; TRANSMEM 465..487; /note="Helical; Name=7"; /evidence="ECO:0000269|PubMed:33199848, ECO:0007744|PDB:6M1Y"; TRANSMEM 519..545; /note="Helical; Name=8"; /evidence="ECO:0000269|PubMed:33199848, ECO:0007744|PDB:6M1Y"; TRANSMEM 569..589; /note="Helical; Name=9"; /evidence="ECO:0000269|PubMed:33199848, ECO:0007744|PDB:6M1Y"; TRANSMEM 590..612; /note="Helical; Name=10"; /evidence="ECO:0000269|PubMed:33199848, ECO:0007744|PDB:6M1Y"; TRANSMEM 630..649; /note="Helical; Name=11"; /evidence="ECO:0000269|PubMed:33199848, ECO:0007744|PDB:6M1Y"; TRANSMEM 650..665; /note="Helical; Name=12"; /evidence="ECO:0007744|PDB:6M1Y
uniprot
proteins