Skip Header

Contribute Send feedback
Read comments (?) or add your own

Q924N4 (S12A6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Solute carrier family 12 member 6
Alternative name(s):
Electroneutral potassium-chloride cotransporter 3
K-Cl cotransporter 3
Gene names
Name:Slc12a6
Synonyms:Kcc3
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length1150 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Mediates electroneutral potassium-chloride cotransport. May be activated by cell swelling. May contribute to cell volume homeostasis in single cells. Ref.5

Enzyme regulation

Inhibited by WNK3 By similarity.

Subunit structure

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

Subcellular location

Basolateral cell membrane; Multi-pass membrane protein Ref.7.

Tissue specificity

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. Ref.7

Post-translational modification

N-glycosylated. Ref.1

Involvement in disease

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. Ref.6

Sequence similarities

Belongs to the SLC12A transporter family.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Stk39Q9Z1W94EBI-620992,EBI-444764

Alternative products

This entry describes 2 isoforms produced by alternative promoter usage. [Align] [Select]
Isoform 1 (identifier: Q924N4-1)

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.
Isoform 2 (identifier: Q924N4-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11501150Solute carrier family 12 member 6
PRO_0000178038

Regions

Topological domain1 – 185185Cytoplasmic Potential
Transmembrane186 – 20621Helical; Potential
Transmembrane208 – 22821Helical; Potential
Topological domain229 – 2357Cytoplasmic Potential
Transmembrane236 – 25621Helical; Potential
Transmembrane277 – 29721Helical; Potential
Topological domain298 – 31922Cytoplasmic Potential
Transmembrane320 – 34021Helical; Potential
Transmembrane343 – 36321Helical; Potential
Topological domain364 – 480117Cytoplasmic Potential
Transmembrane481 – 50121Helical; Potential
Transmembrane518 – 53821Helical; Potential
Topological domain539 – 55820Cytoplasmic Potential
Transmembrane559 – 57921Helical; Potential
Transmembrane632 – 65221Helical; Potential
Topological domain653 – 68937Cytoplasmic Potential
Transmembrane690 – 71021Helical; Potential
Transmembrane789 – 80921Helical; Potential
Topological domain810 – 1150341Cytoplasmic Potential
Compositional bias227 – 2304Poly-Cys

Amino acid modifications

Modified residue321Phosphoserine By similarity
Modified residue10071Phosphoserine Ref.9
Modified residue10321Phosphoserine Ref.8 Ref.9
Glycosylation5041N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 5151Missing in isoform 2.
VSP_006117
Alternative sequence52 – 9039PETSR…QDVTE → MPHFTVTKVEDPEEGAAGPL SPEPSSAEVKARIQDPQEP in isoform 2.
VSP_006118

Experimental info

Sequence conflict9141W → R in AAK81895. Ref.1
Sequence conflict9141W → R in AAK81896. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (KCC3a) [UniParc].

Last modified June 28, 2011. Version 2.
Checksum: 74287FECDBC473BC

FASTA1,150127,527
        10         20         30         40         50         60 
MHPPEATTKM SSVRFMVTPT KIDDIPGLSD TSPDLSSRSS SRVRFSSRES VPETSRSEPM 

        70         80         90        100        110        120 
SELSGATTSL ATVALDPSSD RTSNPQDVTE DPSQNSITGE HSQLLDDGHK KARNAYLNNS 

       130        140        150        160        170        180 
NYEEGDEYFD KNLALFEEEM DTRPKVSSLL NRMANYTNLT QGAKEHEEAE NITEGKKKPT 

       190        200        210        220        230        240 
KSPQMGTFMG VYLPCLQNIF GVILFLRLTW VVGTAGILQA FAIVLICCCC TMLTAISMSA 

       250        260        270        280        290        300 
IATNGVVPAG GSYFMISRAL GPEFGGAVGL CFYLGTTFAA AMYILGAIEI FLVYIVPRAA 

       310        320        330        340        350        360 
IFRSDDALKE SAAMLNNMRV YGTAFLVLMV LVVFIGVRYV NKFASLFLAC VIVSILAIYA 

       370        380        390        400        410        420 
GAIKSSFAPP HFPVCMLGNR TLSSRHLDIC SKTKEVDNMT VPSKLWGFFC NSSQFFNATC 

       430        440        450        460        470        480 
DEYFVHNNVI SIQGIPGLAS GIITENLWSN YLPKGEIIEK PSAKSSDVLG NLNHEYVLAD 

       490        500        510        520        530        540 
ITTSFTLLVG IFFPSVTGIM AGSNRSGDLK DAQKSIPIGT ILAILTTSFV YLSNVVLFGA 

       550        560        570        580        590        600 
CIEGVVLRDK FGDAVKGNLV VGTLSWPSPW VIVIGSFFST CGAGLQSLTG APRLLQAIAK 

       610        620        630        640        650        660 
DNIIPFLRVF GHSKANGEPT WALLLTAAIA ELGILIASLD LVAPILSMFF LMCYLFVNLA 

       670        680        690        700        710        720 
CALQTLLRTP NWRPRFRYYH WALSFMGMSI CLALMFISSW YYAIVAMVIA GMIYKYIEYQ 

       730        740        750        760        770        780 
GAEKEWGDGI RGLSLSAARF ALLRLEEGPP HTKNWRPQLL VLLKLDEDLH VKHPRLLTFA 

       790        800        810        820        830        840 
SQLKAGKGLT IVGSVIVGNF LENYGDALAA EQTIKHLMEA EKVKGFCQLV VAAKLKEGIS 

       850        860        870        880        890        900 
HLIQSCGLGG MKHNTVVMGW PNGWRQSEDA RAWKTFIGTV RVTTAAHLAL LVAKNVSFFP 

       910        920        930        940        950        960 
SNVEQFSEGN IDVWWIVHDG GMLMLLPFLL KQHKVWRKCS IRIFTVAQLE DNSIQMKKDL 

       970        980        990       1000       1010       1020 
ATFLYHLRIE AEVEVVEMHD SDISAYTYER TLMMEQRSQM LRHMRLSKTE RDREAQLVKD 

      1030       1040       1050       1060       1070       1080 
RNSMLRLTSI GSDEDEETET YQEKVHMTWT KDKYMASRGQ KVKSMEGFQD LLNMRPDQSN 

      1090       1100       1110       1120       1130       1140 
VRRMHTAVKL NEVIVNKSHE AKLVLLNMPG PPRNPEGDEN YMEFLEVLTE GLERVLLVRG 

      1150 
GGSEVITIYS

« Hide

Isoform 2 (KCC3b) [UniParc].

Checksum: 8CEA6F2DC4103DB2
Show »

FASTA1,099122,040

References

« Hide 'large scale' references
[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]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
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, 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]"The K-Cl cotransporter KCC3 is mutant in a severe peripheral neuropathy associated with agenesis of the corpus callosum."
Howard H.C., Mount D.B., Rochefort D., Byun N., Dupre N., Lu J., Fan X., Song L., Riviere J.-B., Prevost C., Horst J., Simonati A., Lemcke B., Welch R., England R., Zhan F.Q., Mercado A., Siesser W.B. expand/collapse author list , George A.L. Jr., McDonald M.P., Bouchard J.-P., Mathieu J., Delpire E., Rouleau G.A.
Nat. Genet. 32:384-392(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: DISEASE.
[7]"NH2-terminal heterogeneity in the KCC3 K+-Cl- cotransporter."
Mercado A., Vazquez N., Song L., Cortes R., Enck A.H., Welch R., Delpire E., Gamba G., Mount D.B.
Am. J. Physiol. 289:F1246-1261(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE PROMOTER USAGE, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[8]"Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse synaptosomal preparations."
Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B., Panse C., Schlapbach R., Mansuy I.M.
Mol. Cell. Proteomics 6:283-293(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1032, MASS SPECTROMETRY.
Tissue: Brain cortex.
[9]"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1007 AND SER-1032, MASS SPECTROMETRY.
Tissue: Macrophage.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AF211854 mRNA. Translation: AAK81895.1.
AF211855 mRNA. Translation: AAK81896.1.
AL683897, AL713853 Genomic DNA. Translation: CAM17489.1.
CH466519 Genomic DNA. Translation: EDL27838.1.
IPIIPI00125829.
IPI00857354.
RefSeqNP_598410.2. NM_133649.2.
UniGeneMm.46449.

3D structure databases

ProteinModelPortalQ924N4.
SMRQ924N4. Positions 476-660.
ModBaseSearch...

Protein-protein interaction databases

IntActQ924N4. 2 interactions.

PTM databases

PhosphoSiteQ924N4.

Proteomic databases

PaxDbQ924N4.
PRIDEQ924N4.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000028549; ENSMUSP00000028549; ENSMUSG00000027130.
ENSMUST00000053666; ENSMUSP00000051490; ENSMUSG00000027130.
GeneID107723.
KEGGmmu:107723.

Organism-specific databases

CTD9990.
MGIMGI:2135960. Slc12a6.

Phylogenomic databases

eggNOGCOG0531.
GeneTreeENSGT00560000076892.
HOGENOMHOG000092644.
HOVERGENHBG052852.
InParanoidA2AGK1.
KOK14427.
OMAWTLSFMG.
OrthoDBEOG476JZG.

Gene expression databases

ArrayExpressQ924N4.
BgeeQ924N4.
CleanExMM_SLC12A6.
GenevestigatorQ924N4.
GermOnlineENSMUSG00000027130. Mus musculus.

Family and domain databases

InterProIPR004841. AA-permease_dom.
IPR018491. K/Cl_cotranspt_1/3.
IPR000076. KCL_cotranspt.
IPR004842. Na/K/Cl_cotransptS.
[Graphical view]
PfamPF00324. AA_permease. 2 hits.
PF03522. KCl_Cotrans_1. 1 hit.
[Graphical view]
PRINTSPR01081. KCLTRNSPORT.
TIGRFAMsTIGR00930. 2a30. 1 hit.
ProtoNetSearch...

Other

NextBio359318.
SOURCESearch...

Entry information

Entry nameS12A6_MOUSE
AccessionPrimary (citable) accession number: Q924N4
Secondary accession number(s): A2AGK1, Q924N3
Entry history
Integrated into UniProtKB/Swiss-Prot: December 13, 2002
Last sequence update: June 28, 2011
Last modified: May 1, 2013
This is version 101 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents