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Identification
HMDB Protein ID HMDBP03070
Secondary Accession Numbers
  • 8604
Name Solute carrier family 12 member 6
Synonyms
  1. Electroneutral potassium-chloride cotransporter 3
  2. K-Cl cotransporter 3
Gene Name SLC12A6
Protein Type Transporter
Biological Properties
General Function Involved in transport
Specific Function Mediates electroneutral potassium-chloride cotransport. May be activated by cell swelling. May contribute to cell volume homeostasis in single cells
Pathways
  • Amiloride Action Pathway
  • Bendroflumethiazide Action Pathway
  • Blue diaper syndrome
  • Bumetanide Action Pathway
  • Chlorothiazide Action Pathway
  • Chlorthalidone Action Pathway
  • Cyclothiazide Action Pathway
  • Cystinuria
  • Eplerenone Action Pathway
  • Ethacrynic Acid Action Pathway
  • Furosemide Action Pathway
  • Glucose Transporter Defect (SGLT2)
  • Glucose Transporter Defect (SGLT2)
  • Hartnup Disorder
  • Hydrochlorothiazide Action Pathway
  • Hydroflumethiazide Action Pathway
  • Iminoglycinuria
  • Indapamide Action Pathway
  • Kidney Function
  • Lysinuric Protein Intolerance
  • Lysinuric protein intolerance (LPI)
  • Methyclothiazide Action Pathway
  • Metolazone Action Pathway
  • Polythiazide Action Pathway
  • Quinethazone Action Pathway
  • Spironolactone Action Pathway
  • Torsemide Action Pathway
  • Triamterene Action Pathway
  • Trichlormethiazide Action Pathway
Reactions Not Available
GO Classification
Component
membrane
cell part
membrane part
intrinsic to membrane
integral to membrane
Function
transmembrane transporter activity
substrate-specific transmembrane transporter activity
ion transmembrane transporter activity
transporter activity
anion transmembrane transporter activity
anion:cation symporter activity
cation:chloride symporter activity
Process
sodium ion transport
establishment of localization
transport
chloride transport
transmembrane transport
anion transport
inorganic anion transport
monovalent inorganic cation transport
ion transport
cation transport
Cellular Location
  1. Membrane
  2. Multi-pass membrane protein
Gene Properties
Chromosome Location Chromosome:1
Locus 15q13
SNPs SLC12A6
Gene Sequence
>3453 bp
ATGCATCCTCCAGAAACCACCACCAAGATGGCTTCAGTTCGGTTCATGGTGACACCGACA
AAGATCGATGACATTCCAGGTTTGTCAGACACCAGTCCGGACCTCAGCTCTCGATCTAGT
TCCCGAGTAAGATTTAGCTCCCGGGAAAGCGTGCCTGAAACAAGCCGGAGTGAGCCTATG
AGTGAGATGTCTGGGGCCACCACTTCGCTGGCAACTGTTGCACTGGATCCACCCAGTGAC
CGGACTTCTCACCCCCAGGATGTCATCGAGGACCTGAGTCAGAACTCCATCACAGGGGAA
CACAGCCAACTGTTAGACGACGGACATAAGAAAGCTCGAAATGCTTATCTCAATAATTCC
AATTATGAAGAAGGAGATGAATATTTTGATAAAAATTTGGCACTCTTTGAGGAAGAAATG
GACACCAGACCGAAGGTGTCTTCCCTCCTCAACCGCATGGCCAATTACACTAATCTGACT
CAAGGAGCAAAGGAACATGAAGAGGCAGAAAACATCACTGAAGGGAAAAAGAAGCCCACC
AAGACCCCCCAAATGGGTACCTTCATGGGTGTCTACCTCCCATGTCTACAAAATATTTTT
GGAGTGATCCTTTTTTTACGCCTTACATGGGTGGTGGGCACAGCTGGAGTTCTTCAGGCT
TTTGCAATTGTCCTTATCTGCTGCTGCTGTACAATGTTGACTGCTATCTCCATGAGTGCC
ATTGCCACTAATGGAGTGGTGCCAGCTGGGGGCTCATACTTTATGATTTCCCGGGCACTG
GGCCCAGAGTTTGGTGGGGCTGTTGGCCTCTGCTTTTATCTTGGTACCACATTTGCAGCA
GCCATGTACATCCTTGGTGCCATTGAAATCTTTCTGGTCTATATCGTCCCCCGAGCTGCC
ATCTTTCACAGTGATGACGCACTCAAGGAATCAGCAGCCATGCTAAATAACATGCGTGTC
TACGGCACAGCTTTCTTGGTCCTTATGGTATTAGTGGTATTTATCGGCGTACGCTATGTG
AACAAGTTTGCCTCACTTTTCCTGGCCTGTGTCATTGTGTCCATCTTGGCCATCTATGCT
GGAGCCATCAAGTCTTCTTTTGCTCCTCCACACTTCCCGGTCTGCATGCTGGGTAACCGC
ACTCTTTCATCAAGACACATTGACGTTTGCTCTAAGACCAAGGAAATTAACAACATGACA
GTCCCATCAAAGTTATGGGGATTCTTCTGTAACTCGAGTCAATTTTTCAATGCCACCTGT
GATGAATACTTTGTTCACAATAACGTCACTTCAATCCAGGGCATTCCTGGATTGGCTAGT
GGTATAATTACAGAGAATCTTTGGAGTAATTACCTACCCAAGGGAGAGATCATCGAAAAG
CCTTCAGCCAAATCTTCTGATGTCTTAGGCAGCTTAAACCATGAATATGTTCTTGTTGAC
ATCACCACCTCCTTCACGCTTCTGGTGGGAATCTTCTTTCCCTCTGTTACAGGTATCATG
GCTGGATCAAACAGATCTGGAGATCTGAAAGATGCTCAGAAGTCTATTCCGATTGGTACT
ATCCTTGCCATCCTGACCACCTCCTTTGTTTATTTAAGCAATGTTGTCCTTTTTGGTGCA
TGTATTGAAGGGGTTGTTCTCAGAGACAAGTTCGGTGATGCTGTGAAAGGTAATTTGGTG
GTAGGCACCTTATCTTGGCCATCCCCATGGGTGATTGTTATTGGCTCCTTCTTTTCAACA
TGTGGGGCTGGACTTCAGAGCCTCACAGGTGCACCGAGGCTGCTACAAGCTATTGCCAAG
GATAACATCATACCGTTTCTGAGGGTTTTTGGCCACAGCAAAGCCAATGGGGAACCTACC
TGGGCTTTACTTCTAACTGCTGCCATTGCAGAGCTTGGAATACTCATTGCCTCCCTGGAT
CTTGTGGCCCCAATTCTTTCCATGTTTTTTCTCATGTGTTACCTCTTTGTAAACTTGGCA
TGTGCCTTGCAAACATTACTTCGAACACCCAACTGGAGACCCCGATTCCGCTACTACCAT
TGGGCCCTTTCTTTCATGGGAATGAGTATCTGTCTGGCTCTGATGTTCATTTCTTCCTGG
TATTATGCCATTGTAGCCATGGTAATAGCTGGTATGATCTACAAGTACATTGAATACCAA
GGAGCTGAGAAAGAATGGGGTGATGGTATCCGTGGGCTGTCCCTCAGTGCAGCCCGGTTT
GCTTTGCTTCGATTGGAGGAAGGACCTCCACACACTAAAAACTGGAGGCCTCAGTTGCTT
GTATTACTGAAACTAGATGAAGACTTACATGTCAAGCATCCTCGCCTCCTCACCTTTGCC
TCACAGCTCAAAGCAGGAAAAGGTCTCACTATTGTGGGCTCTGTCATCGTGGGGAACTTC
CTAGAGAACTACGGTGAAGCTTTAGCTGCTGAGCAGACCATAAAGCACCTAATGGAGGCA
GAGAAGGTAAAAGGATTCTGCCAGCTGGTGGTGGCCGCCAAGCTGAGAGAGGGCATTTCC
CACCTCATCCAGTCATGTGGCCTTGGGGGCATGAAGCACAACACGGTGGTGATGGGCTGG
CCTAATGGCTGGCGTCAAAGCGAAGATGCCCGCGCTTGGAAGACTTTTATTGGCACAGTT
CGAGTGACAACTGCTGCCCATCTTGCACTGCTGGTGGCTAAAAACATCTCCTTCTTTCCC
AGCAATGTGGAGCAATTTTCTGAGGGCAACATTGATGTGTGGTGGATTGTGCATGATGGG
GGGATGCTTATGCTACTACCATTCCTACTGAAACAGCACAAGGTGTGGCGAAAGTGCAGC
ATACGGATCTTCACAGTAGCCCAATTAGAAGACAACAGTATCCAAATGAAGAAGGACCTA
GCCACCTTCCTATATCACTTACGCATTGAGGCGGAGGTAGAAGTGGTGGAGATGCATGAC
AGTGATATATCAGCATATACTTACGAGCGCACTTTGATGATGGAACAAAGGTCCCAGATG
CTTCGGCACATGCGGCTATCCAAAACAGAGCGAGACAGAGAGGCACAATTGGTGAAAGAC
CGAAACTCAATGCTACGATTGACCAGCATTGGCTCTGATGAGGACGAAGAGACAGAAACC
TATCAGGAGAAGGTGCACATGACTTGGACAAAAGACAAGTACATGGCATCCCGGGGACAA
AAAGCGAAGTCAATGGAAGGATTCCAGGACCTGCTTAACATGCGTCCGGACCAGTCCAAT
GTGAGGCGGATGCATACAGCAGTGAAACTCAACGAGGTTATAGTTAACAAGTCCCATGAA
GCAAAGCTGGTTTTATTGAATATGCCAGGGCCACCCCGAAACCCTGAGGGTGATGAAAAC
TACATGGAGTTCCTAGAGGTGCTTACCGAGGGACTAGAGCGAGTCCTACTTGTCCGGGGT
GGTGGCAGTGAAGTGATCACCATTTATTCATAA
Protein Properties
Number of Residues 1150
Molecular Weight 127615.7
Theoretical pI 7.08
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • 186-206
  • 208-228
  • 236-256
  • 277-297
  • 320-340
  • 343-363
  • 481-501
  • 518-538
  • 559-579
  • 632-652
  • 690-710
  • 910-930
Protein Sequence
>Solute carrier family 12 member 6
MHPPETTTKMASVRFMVTPTKIDDIPGLSDTSPDLSSRSSSRVRFSSRESVPETSRSEPM
SEMSGATTSLATVALDPPSDRTSHPQDVIEDLSQNSITGEHSQLLDDGHKKARNAYLNNS
NYEEGDEYFDKNLALFEEEMDTRPKVSSLLNRMANYTNLTQGAKEHEEAENITEGKKKPT
KTPQMGTFMGVYLPCLQNIFGVILFLRLTWVVGTAGVLQAFAIVLICCCCTMLTAISMSA
IATNGVVPAGGSYFMISRALGPEFGGAVGLCFYLGTTFAAAMYILGAIEIFLVYIVPRAA
IFHSDDALKESAAMLNNMRVYGTAFLVLMVLVVFIGVRYVNKFASLFLACVIVSILAIYA
GAIKSSFAPPHFPVCMLGNRTLSSRHIDVCSKTKEINNMTVPSKLWGFFCNSSQFFNATC
DEYFVHNNVTSIQGIPGLASGIITENLWSNYLPKGEIIEKPSAKSSDVLGSLNHEYVLVD
ITTSFTLLVGIFFPSVTGIMAGSNRSGDLKDAQKSIPIGTILAILTTSFVYLSNVVLFGA
CIEGVVLRDKFGDAVKGNLVVGTLSWPSPWVIVIGSFFSTCGAGLQSLTGAPRLLQAIAK
DNIIPFLRVFGHSKANGEPTWALLLTAAIAELGILIASLDLVAPILSMFFLMCYLFVNLA
CALQTLLRTPNWRPRFRYYHWALSFMGMSICLALMFISSWYYAIVAMVIAGMIYKYIEYQ
GAEKEWGDGIRGLSLSAARFALLRLEEGPPHTKNWRPQLLVLLKLDEDLHVKHPRLLTFA
SQLKAGKGLTIVGSVIVGNFLENYGEALAAEQTIKHLMEAEKVKGFCQLVVAAKLREGIS
HLIQSCGLGGMKHNTVVMGWPNGWRQSEDARAWKTFIGTVRVTTAAHLALLVAKNISFFP
SNVEQFSEGNIDVWWIVHDGGMLMLLPFLLKQHKVWRKCSIRIFTVAQLEDNSIQMKKDL
ATFLYHLRIEAEVEVVEMHDSDISAYTYERTLMMEQRSQMLRHMRLSKTERDREAQLVKD
RNSMLRLTSIGSDEDEETETYQEKVHMTWTKDKYMASRGQKAKSMEGFQDLLNMRPDQSN
VRRMHTAVKLNEVIVNKSHEAKLVLLNMPGPPRNPEGDENYMEFLEVLTEGLERVLLVRG
GGSEVITIYS
GenBank ID Protein 5106523
UniProtKB/Swiss-Prot ID Q9UHW9
UniProtKB/Swiss-Prot Entry Name S12A6_HUMAN
PDB IDs Not Available
GenBank Gene ID AF105366
GeneCard ID SLC12A6
GenAtlas ID SLC12A6
HGNC ID HGNC:10914
References
General References
  1. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  2. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332 ]
  3. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [PubMed:17974005 ]
  4. Casula S, Shmukler BE, Wilhelm S, Stuart-Tilley AK, Su W, Chernova MN, Brugnara C, Alper SL: A dominant negative mutant of the KCC1 K-Cl cotransporter: both N- and C-terminal cytoplasmic domains are required for K-Cl cotransport activity. J Biol Chem. 2001 Nov 9;276(45):41870-8. Epub 2001 Sep 10. [PubMed:11551954 ]
  5. Race JE, Makhlouf FN, Logue PJ, Wilson FH, Dunham PB, Holtzman EJ: Molecular cloning and functional characterization of KCC3, a new K-Cl cotransporter. Am J Physiol. 1999 Dec;277(6 Pt 1):C1210-9. [PubMed:10600773 ]
  6. Hiki K, D'Andrea RJ, Furze J, Crawford J, Woollatt E, Sutherland GR, Vadas MA, Gamble JR: Cloning, characterization, and chromosomal location of a novel human K+-Cl- cotransporter. J Biol Chem. 1999 Apr 9;274(15):10661-7. [PubMed:10187864 ]
  7. Mount DB, Mercado A, Song L, Xu J, George AL Jr, Delpire E, Gamba G: Cloning and characterization of KCC3 and KCC4, new members of the cation-chloride cotransporter gene family. J Biol Chem. 1999 Jun 4;274(23):16355-62. [PubMed:10347194 ]
  8. Howard HC, Mount DB, Rochefort D, Byun N, Dupre N, Lu J, Fan X, Song L, Riviere JB, Prevost C, Horst J, Simonati A, Lemcke B, Welch R, England R, Zhan FQ, Mercado A, Siesser WB, George AL Jr, McDonald MP, Bouchard JP, Mathieu J, Delpire E, Rouleau GA: The K-Cl cotransporter KCC3 is mutant in a severe peripheral neuropathy associated with agenesis of the corpus callosum. Nat Genet. 2002 Nov;32(3):384-92. Epub 2002 Oct 7. [PubMed:12368912 ]