Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
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

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Ion transport, Potassium transport, Symport, Transport

Keywords - Ligandi

Potassium

Enzyme and pathway databases

ReactomeiR-MMU-426117. 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
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:2135960. Slc12a6.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 185CytoplasmicSequence analysisAdd BLAST185
Transmembranei186 – 206HelicalSequence analysisAdd BLAST21
Transmembranei208 – 228HelicalSequence analysisAdd BLAST21
Topological domaini229 – 235CytoplasmicSequence analysis7
Transmembranei236 – 256HelicalSequence analysisAdd BLAST21
Transmembranei277 – 297HelicalSequence analysisAdd BLAST21
Topological domaini298 – 319CytoplasmicSequence analysisAdd BLAST22
Transmembranei320 – 340HelicalSequence analysisAdd BLAST21
Transmembranei343 – 363HelicalSequence analysisAdd BLAST21
Topological domaini364 – 480CytoplasmicSequence analysisAdd BLAST117
Transmembranei481 – 501HelicalSequence analysisAdd BLAST21
Transmembranei518 – 538HelicalSequence analysisAdd BLAST21
Topological domaini539 – 558CytoplasmicSequence analysisAdd BLAST20
Transmembranei559 – 579HelicalSequence analysisAdd BLAST21
Transmembranei632 – 652HelicalSequence analysisAdd BLAST21
Topological domaini653 – 689CytoplasmicSequence analysisAdd BLAST37
Transmembranei690 – 710HelicalSequence analysisAdd BLAST21
Transmembranei789 – 809HelicalSequence analysisAdd BLAST21
Topological domaini810 – 1150CytoplasmicSequence analysisAdd BLAST341

GO - Cellular componenti

  • axon Source: MGI
  • basolateral plasma membrane Source: UniProtKB
  • integral component of plasma membrane Source: InterPro
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)DescriptionActionsGraphical viewLength
ChainiPRO_00001780381 – 1150Solute carrier family 12 member 6Add BLAST1150

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei32PhosphoserineBy similarity1
Modified residuei120PhosphoserineBy similarity1
Modified residuei148PhosphoserineBy similarity1
Glycosylationi504N-linked (GlcNAc...)Sequence analysis1
Modified residuei1032PhosphoserineBy similarity1

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ924N4.
PeptideAtlasiQ924N4.
PRIDEiQ924N4.

PTM databases

iPTMnetiQ924N4.
PhosphoSitePlusiQ924N4.

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

BgeeiENSMUSG00000027130.
CleanExiMM_SLC12A6.
ExpressionAtlasiQ924N4. baseline and differential.
GenevisibleiQ924N4. MM.

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. 4 interactors.
STRINGi10090.ENSMUSP00000028549.

Structurei

3D structure databases

ProteinModelPortaliQ924N4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi227 – 230Poly-Cys4

Sequence similaritiesi

Belongs to the SLC12A transporter family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2082. Eukaryota.
COG0531. LUCA.
GeneTreeiENSGT00760000119053.
HOGENOMiHOG000092644.
HOVERGENiHBG052852.
InParanoidiQ924N4.
KOiK14427.
OMAiDRTSHPQ.
OrthoDBiEOG091G0WB4.
TreeFamiTF313657.

Family and domain databases

InterProiIPR004841. AA-permease/SLC12A_dom.
IPR030364. KCC3.
IPR000076. KCL_cotranspt.
IPR018491. SLC12_C.
IPR004842. SLC12A_fam.
[Graphical view]
PANTHERiPTHR11827:SF66. PTHR11827:SF66. 4 hits.
PfamiPF00324. AA_permease. 2 hits.
PF03522. SLC12. 2 hits.
[Graphical view]
PRINTSiPR01081. KCLTRNSPORT.
TIGRFAMsiTIGR00930. 2a30. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative promoter usage. AlignAdd to basket

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)DescriptionActionsGraphical viewLength
Sequence conflicti914W → R in AAK81895 (PubMed:11246162).Curated1
Sequence conflicti914W → R in AAK81896 (PubMed:11246162).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0061171 – 51Missing in isoform 2. 1 PublicationAdd BLAST51
Alternative sequenceiVSP_00611852 – 90PETSR…QDVTE → MPHFTVTKVEDPEEGAAGPL SPEPSSAEVKARIQDPQEP in isoform 2. 1 PublicationAdd BLAST39

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]
uc008low.2. mouse. [Q924N4-2]

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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ924N4. 4 interactors.
STRINGi10090.ENSMUSP00000028549.

PTM databases

iPTMnetiQ924N4.
PhosphoSitePlusiQ924N4.

Proteomic databases

PaxDbiQ924N4.
PeptideAtlasiQ924N4.
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]
uc008low.2. mouse. [Q924N4-2]

Organism-specific databases

CTDi9990.
MGIiMGI:2135960. Slc12a6.

Phylogenomic databases

eggNOGiKOG2082. Eukaryota.
COG0531. LUCA.
GeneTreeiENSGT00760000119053.
HOGENOMiHOG000092644.
HOVERGENiHBG052852.
InParanoidiQ924N4.
KOiK14427.
OMAiDRTSHPQ.
OrthoDBiEOG091G0WB4.
TreeFamiTF313657.

Enzyme and pathway databases

ReactomeiR-MMU-426117. Cation-coupled Chloride cotransporters.

Miscellaneous databases

ChiTaRSiSlc12a6. mouse.
PROiQ924N4.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000027130.
CleanExiMM_SLC12A6.
ExpressionAtlasiQ924N4. baseline and differential.
GenevisibleiQ924N4. MM.

Family and domain databases

InterProiIPR004841. AA-permease/SLC12A_dom.
IPR030364. KCC3.
IPR000076. KCL_cotranspt.
IPR018491. SLC12_C.
IPR004842. SLC12A_fam.
[Graphical view]
PANTHERiPTHR11827:SF66. PTHR11827:SF66. 4 hits.
PfamiPF00324. AA_permease. 2 hits.
PF03522. SLC12. 2 hits.
[Graphical view]
PRINTSiPR01081. KCLTRNSPORT.
TIGRFAMsiTIGR00930. 2a30. 1 hit.
ProtoNetiSearch...

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: November 2, 2016
This is version 133 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

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 one 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.