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Protein

Solute carrier family 12 member 6

Gene

Slc12a6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Mediates electroneutral potassium-chloride cotransport. May be activated by cell swelling. May contribute to cell volume homeostasis in single cells.1 Publication

Enzyme regulationi

Inhibited by WNK3.By similarity

GO - Molecular functioni

  1. potassium:chloride symporter activity Source: UniProtKB

GO - Biological processi

  1. cellular hypotonic salinity response Source: UniProtKB
  2. chloride transmembrane transport Source: GOC
  3. chloride transport Source: GOC
  4. potassium ion transport Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Ion transport, Potassium transport, Symport, Transport

Keywords - Ligandi

Potassium

Enzyme and pathway databases

ReactomeiREACT_247880. Cation-coupled Chloride cotransporters.

Names & Taxonomyi

Protein namesi
Recommended name:
Solute carrier family 12 member 6
Alternative name(s):
Electroneutral potassium-chloride cotransporter 3
K-Cl cotransporter 3
Gene namesi
Name:Slc12a6
Synonyms:Kcc3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 2

Organism-specific databases

MGIiMGI:2135960. Slc12a6.

Subcellular locationi

Basolateral cell membrane 1 Publication; Multi-pass membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 185185CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei186 – 20621HelicalSequence AnalysisAdd
BLAST
Transmembranei208 – 22821HelicalSequence AnalysisAdd
BLAST
Topological domaini229 – 2357CytoplasmicSequence Analysis
Transmembranei236 – 25621HelicalSequence AnalysisAdd
BLAST
Transmembranei277 – 29721HelicalSequence AnalysisAdd
BLAST
Topological domaini298 – 31922CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei320 – 34021HelicalSequence AnalysisAdd
BLAST
Transmembranei343 – 36321HelicalSequence AnalysisAdd
BLAST
Topological domaini364 – 480117CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei481 – 50121HelicalSequence AnalysisAdd
BLAST
Transmembranei518 – 53821HelicalSequence AnalysisAdd
BLAST
Topological domaini539 – 55820CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei559 – 57921HelicalSequence AnalysisAdd
BLAST
Transmembranei632 – 65221HelicalSequence AnalysisAdd
BLAST
Topological domaini653 – 68937CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei690 – 71021HelicalSequence AnalysisAdd
BLAST
Transmembranei789 – 80921HelicalSequence AnalysisAdd
BLAST
Topological domaini810 – 1150341CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. basolateral plasma membrane Source: UniProtKB
  2. integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Defects in Slc12a6 are a cause of locomotor abnormalities beginning at 2 weeks of age. Slc12a6 deficient mice show hypomyelination, decompaction of myelin, demyelination, axonal swelling and fiber degeneration.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11501150Solute carrier family 12 member 6PRO_0000178038Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei32 – 321PhosphoserineBy similarity
Glycosylationi504 – 5041N-linked (GlcNAc...)Sequence Analysis
Modified residuei1032 – 10321PhosphoserineBy similarity

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ924N4.
PaxDbiQ924N4.
PRIDEiQ924N4.

PTM databases

PhosphoSiteiQ924N4.

Expressioni

Tissue specificityi

Isoform 1 is highly expressed throughout the brain and detected at lower levels in kidney. Highly expressed in highly myelinated white matter of the brain, but not in gray matter. Detected in the corpus callosum, in packed cell layers of the hippocampus and in Purkinje neurons within the cerebellum. Highly expressed in white matter in the spinal cord, but not in dorsal root ganglia or sciatic nerve. Colocalizes with the oligodendrocyte marker CNP. Isoform 2 is highly expressed in kidney, but not detected in brain.1 Publication

Gene expression databases

BgeeiQ924N4.
CleanExiMM_SLC12A6.
ExpressionAtlasiQ924N4. baseline and differential.
GenevestigatoriQ924N4.

Interactioni

Subunit structurei

Homomultimer and heteromultimer with other K-Cl cotransporters.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Stk39Q9Z1W94EBI-620992,EBI-444764

Protein-protein interaction databases

IntActiQ924N4. 2 interactions.

Structurei

3D structure databases

ProteinModelPortaliQ924N4.
SMRiQ924N4. Positions 476-660.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi227 – 2304Poly-Cys

Sequence similaritiesi

Belongs to the SLC12A transporter family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0531.
GeneTreeiENSGT00760000119053.
HOGENOMiHOG000092644.
HOVERGENiHBG052852.
InParanoidiQ924N4.
KOiK14427.
OMAiNPQDVTE.
TreeFamiTF313657.

Family and domain databases

InterProiIPR004841. AA-permease/SLC12A_dom.
IPR018491. K/Cl_cotranspt_1/3.
IPR030364. KCC3.
IPR000076. KCL_cotranspt.
IPR004842. Na/K/Cl_cotransptS.
[Graphical view]
PANTHERiPTHR11827:SF51. PTHR11827:SF51. 1 hit.
PfamiPF00324. AA_permease. 2 hits.
PF03522. KCl_Cotrans_1. 1 hit.
[Graphical view]
PRINTSiPR01081. KCLTRNSPORT.
TIGRFAMsiTIGR00930. 2a30. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative promoter usage. Align

Isoform 1 (identifier: Q924N4-1) [UniParc]FASTAAdd to Basket

Also known as: KCC3a

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MHPPEATTKM SSVRFMVTPT KIDDIPGLSD TSPDLSSRSS SRVRFSSRES
60 70 80 90 100
VPETSRSEPM SELSGATTSL ATVALDPSSD RTSNPQDVTE DPSQNSITGE
110 120 130 140 150
HSQLLDDGHK KARNAYLNNS NYEEGDEYFD KNLALFEEEM DTRPKVSSLL
160 170 180 190 200
NRMANYTNLT QGAKEHEEAE NITEGKKKPT KSPQMGTFMG VYLPCLQNIF
210 220 230 240 250
GVILFLRLTW VVGTAGILQA FAIVLICCCC TMLTAISMSA IATNGVVPAG
260 270 280 290 300
GSYFMISRAL GPEFGGAVGL CFYLGTTFAA AMYILGAIEI FLVYIVPRAA
310 320 330 340 350
IFRSDDALKE SAAMLNNMRV YGTAFLVLMV LVVFIGVRYV NKFASLFLAC
360 370 380 390 400
VIVSILAIYA GAIKSSFAPP HFPVCMLGNR TLSSRHLDIC SKTKEVDNMT
410 420 430 440 450
VPSKLWGFFC NSSQFFNATC DEYFVHNNVI SIQGIPGLAS GIITENLWSN
460 470 480 490 500
YLPKGEIIEK PSAKSSDVLG NLNHEYVLAD ITTSFTLLVG IFFPSVTGIM
510 520 530 540 550
AGSNRSGDLK DAQKSIPIGT ILAILTTSFV YLSNVVLFGA CIEGVVLRDK
560 570 580 590 600
FGDAVKGNLV VGTLSWPSPW VIVIGSFFST CGAGLQSLTG APRLLQAIAK
610 620 630 640 650
DNIIPFLRVF GHSKANGEPT WALLLTAAIA ELGILIASLD LVAPILSMFF
660 670 680 690 700
LMCYLFVNLA CALQTLLRTP NWRPRFRYYH WALSFMGMSI CLALMFISSW
710 720 730 740 750
YYAIVAMVIA GMIYKYIEYQ GAEKEWGDGI RGLSLSAARF ALLRLEEGPP
760 770 780 790 800
HTKNWRPQLL VLLKLDEDLH VKHPRLLTFA SQLKAGKGLT IVGSVIVGNF
810 820 830 840 850
LENYGDALAA EQTIKHLMEA EKVKGFCQLV VAAKLKEGIS HLIQSCGLGG
860 870 880 890 900
MKHNTVVMGW PNGWRQSEDA RAWKTFIGTV RVTTAAHLAL LVAKNVSFFP
910 920 930 940 950
SNVEQFSEGN IDVWWIVHDG GMLMLLPFLL KQHKVWRKCS IRIFTVAQLE
960 970 980 990 1000
DNSIQMKKDL ATFLYHLRIE AEVEVVEMHD SDISAYTYER TLMMEQRSQM
1010 1020 1030 1040 1050
LRHMRLSKTE RDREAQLVKD RNSMLRLTSI GSDEDEETET YQEKVHMTWT
1060 1070 1080 1090 1100
KDKYMASRGQ KVKSMEGFQD LLNMRPDQSN VRRMHTAVKL NEVIVNKSHE
1110 1120 1130 1140 1150
AKLVLLNMPG PPRNPEGDEN YMEFLEVLTE GLERVLLVRG GGSEVITIYS
Length:1,150
Mass (Da):127,527
Last modified:June 28, 2011 - v2
Checksum:i74287FECDBC473BC
GO
Isoform 2 (identifier: Q924N4-2) [UniParc]FASTAAdd to Basket

Also known as: KCC3b

The sequence of this isoform differs from the canonical sequence as follows:
     1-51: Missing.
     52-90: PETSRSEPMS...RTSNPQDVTE → MPHFTVTKVE...KARIQDPQEP

Note: Produced by alternative promoter usage.

Show »
Length:1,099
Mass (Da):122,040
Checksum:i8CEA6F2DC4103DB2
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti914 – 9141W → R in AAK81895. (PubMed:11246162)Curated
Sequence conflicti914 – 9141W → R in AAK81896. (PubMed:11246162)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 5151Missing in isoform 2. 1 PublicationVSP_006117Add
BLAST
Alternative sequencei52 – 9039PETSR…QDVTE → MPHFTVTKVEDPEEGAAGPL SPEPSSAEVKARIQDPQEP in isoform 2. 1 PublicationVSP_006118Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF211854 mRNA. Translation: AAK81895.1.
AF211855 mRNA. Translation: AAK81896.1.
AL683897, AL713853 Genomic DNA. Translation: CAM17489.1.
CH466519 Genomic DNA. Translation: EDL27838.1.
CCDSiCCDS16551.1. [Q924N4-1]
CCDS16552.1. [Q924N4-2]
RefSeqiNP_598410.2. NM_133649.2. [Q924N4-1]
UniGeneiMm.491155.

Genome annotation databases

EnsembliENSMUST00000028549; ENSMUSP00000028549; ENSMUSG00000027130. [Q924N4-1]
ENSMUST00000053666; ENSMUSP00000051490; ENSMUSG00000027130. [Q924N4-2]
GeneIDi107723.
KEGGimmu:107723.
UCSCiuc008lou.2. mouse. [Q924N4-1]

Keywords - Coding sequence diversityi

Alternative promoter usage

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF211854 mRNA. Translation: AAK81895.1.
AF211855 mRNA. Translation: AAK81896.1.
AL683897, AL713853 Genomic DNA. Translation: CAM17489.1.
CH466519 Genomic DNA. Translation: EDL27838.1.
CCDSiCCDS16551.1. [Q924N4-1]
CCDS16552.1. [Q924N4-2]
RefSeqiNP_598410.2. NM_133649.2. [Q924N4-1]
UniGeneiMm.491155.

3D structure databases

ProteinModelPortaliQ924N4.
SMRiQ924N4. Positions 476-660.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ924N4. 2 interactions.

PTM databases

PhosphoSiteiQ924N4.

Proteomic databases

MaxQBiQ924N4.
PaxDbiQ924N4.
PRIDEiQ924N4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000028549; ENSMUSP00000028549; ENSMUSG00000027130. [Q924N4-1]
ENSMUST00000053666; ENSMUSP00000051490; ENSMUSG00000027130. [Q924N4-2]
GeneIDi107723.
KEGGimmu:107723.
UCSCiuc008lou.2. mouse. [Q924N4-1]

Organism-specific databases

CTDi9990.
MGIiMGI:2135960. Slc12a6.

Phylogenomic databases

eggNOGiCOG0531.
GeneTreeiENSGT00760000119053.
HOGENOMiHOG000092644.
HOVERGENiHBG052852.
InParanoidiQ924N4.
KOiK14427.
OMAiNPQDVTE.
TreeFamiTF313657.

Enzyme and pathway databases

ReactomeiREACT_247880. Cation-coupled Chloride cotransporters.

Miscellaneous databases

ChiTaRSiSlc12a6. mouse.
NextBioi359318.
PROiQ924N4.
SOURCEiSearch...

Gene expression databases

BgeeiQ924N4.
CleanExiMM_SLC12A6.
ExpressionAtlasiQ924N4. baseline and differential.
GenevestigatoriQ924N4.

Family and domain databases

InterProiIPR004841. AA-permease/SLC12A_dom.
IPR018491. K/Cl_cotranspt_1/3.
IPR030364. KCC3.
IPR000076. KCL_cotranspt.
IPR004842. Na/K/Cl_cotransptS.
[Graphical view]
PANTHERiPTHR11827:SF51. PTHR11827:SF51. 1 hit.
PfamiPF00324. AA_permease. 2 hits.
PF03522. KCl_Cotrans_1. 1 hit.
[Graphical view]
PRINTSiPR01081. KCLTRNSPORT.
TIGRFAMsiTIGR00930. 2a30. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Localization of the K(+)-Cl(-) cotransporter, KCC3, in the central and peripheral nervous systems: expression in the choroid plexus, large neurons and white matter tracts."
    Pearson M.M., Lu J., Mount D.B., Delpire E.
    Neuroscience 103:481-491(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), GLYCOSYLATION.
    Strain: C57BL/6J.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  3. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. Lubec G., Kang S.U.
    Submitted (APR-2007) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 601-608; 1054-1061 AND 1103-1113, IDENTIFICATION BY MASS SPECTROMETRY.
    Strain: C57BL/6.
    Tissue: Brain.
  5. "Cloning and characterization of KCC3 and KCC4, new members of the cation-chloride cotransporter gene family."
    Mount D.B., Mercado A., Song L., Xu J., George A.L. Jr., Delpire E., Gamba G.
    J. Biol. Chem. 274:16355-16362(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. Cited for: DISEASE.
  7. Cited for: ALTERNATIVE PROMOTER USAGE, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
  8. "The phagosomal proteome in interferon-gamma-activated macrophages."
    Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
    Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiS12A6_MOUSE
AccessioniPrimary (citable) accession number: Q924N4
Secondary accession number(s): A2AGK1, Q924N3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 13, 2002
Last sequence update: June 28, 2011
Last modified: January 7, 2015
This is version 117 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.