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Q9Y666 (S12A7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Solute carrier family 12 member 7
Alternative name(s):
Electroneutral potassium-chloride cotransporter 4
K-Cl cotransporter 4
Gene names
Name:SLC12A7
Synonyms:KCC4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1083 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Mediates electroneutral potassium-chloride cotransport when activated by cell swelling. May mediate K+ uptake into Deiters' cells in the cochlea and contribute to K+ recycling in the inner ear. Important for the survival of cochlear outer and inner hair cells and the maintenance of the organ of Corti. May be required for basolateral Cl- extrusion in the kidney and contribute to renal acidification By similarity. Ref.6

Enzyme regulation

Activated by N-ethylmaleimide (NEM). Inhibited by furosemide, DIDS and bumetanide. The inhibition is much stronger in the presence of 50 mM K+ in the uptake medium. Inhibited by DIOA. Inhibited by WNK3. Ref.9

Subunit structure

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

Subcellular location

Cell membrane; Multi-pass membrane protein.

Tissue specificity

Detected in muscle, brain, lung, heart and kidney.

Sequence similarities

Belongs to the SLC12A transporter family.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9Y666-1)

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: Q9Y666-2)

The sequence of this isoform differs from the canonical sequence as follows:
     227-266: YISPGAAIFQ...CTLVLMALVV → GTEDGVGSLG...AAHGASYGSF
     267-1083: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10831083Solute carrier family 12 member 7
PRO_0000178039

Regions

Topological domain1 – 118118Cytoplasmic Potential
Transmembrane119 – 13921Helical; Potential
Transmembrane141 – 16121Helical; Potential
Topological domain162 – 21453Cytoplasmic Potential
Transmembrane215 – 23521Helical; Potential
Transmembrane253 – 27321Helical; Potential
Topological domain274 – 2752Cytoplasmic Potential
Transmembrane276 – 29621Helical; Potential
Transmembrane416 – 43621Helical; Potential
Topological domain437 – 45620Cytoplasmic Potential
Transmembrane457 – 47721Helical; Potential
Transmembrane494 – 51421Helical; Potential
Topological domain515 – 55339Cytoplasmic Potential
Transmembrane554 – 57421Helical; Potential
Transmembrane578 – 59821Helical; Potential
Topological domain599 – 62426Cytoplasmic Potential
Transmembrane625 – 64521Helical; Potential
Transmembrane845 – 86521Helical; Potential
Topological domain866 – 1083218Cytoplasmic Potential

Amino acid modifications

Modified residue501Phosphoserine Ref.8
Modified residue621Phosphoserine Ref.8
Glycosylation3121N-linked (GlcNAc...) Potential
Glycosylation3601N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence227 – 26640YISPG…MALVV → GTEDGVGSLGLGLAQGNRRQ THLSPSDAAQAAHGASYGSF in isoform 2.
VSP_006119
Alternative sequence267 – 1083817Missing in isoform 2.
VSP_006120
Natural variant4081A → T. Ref.1
Corresponds to variant rs4526148 [ dbSNP | Ensembl ].
VAR_028748

Experimental info

Sequence conflict5221S → T in AAD39741. Ref.1

Sequences

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

Last modified December 4, 2007. Version 3.
Checksum: BF50134614BF6617

FASTA1,083119,106
        10         20         30         40         50         60 
MPTNFTVVPV EAHADGGGDE TAERTEAPGT PEGPEPERPS PGDGNPRENS PFLNNVEVEQ 

        70         80         90        100        110        120 
ESFFEGKNMA LFEEEMDSNP MVSSLLNKLA NYTNLSQGVV EHEEDEESRR REAKAPRMGT 

       130        140        150        160        170        180 
FIGVYLPCLQ NILGVILFLR LTWIVGVAGV LESFLIVAMC CTCTMLTAIS MSAIATNGVV 

       190        200        210        220        230        240 
PAGGSYYMIS RSLGPEFGGA VGLCFYLGTT FAGAMYILGT IEIFLTYISP GAAIFQAEAA 

       250        260        270        280        290        300 
GGEAAAMLHN MRVYGTCTLV LMALVVFVGV KYVNKLALVF LACVVLSILA IYAGVIKSAF 

       310        320        330        340        350        360 
DPPDIPVCLL GNRTLSRRSF DACVKAYGIH NNSATSALWG LFCNGSQPSA ACDEYFIQNN 

       370        380        390        400        410        420 
VTEIQGIPGA ASGVFLENLW STYAHAGAFV EKKGVPSVPV AEESRASALP YVLTDIAASF 

       430        440        450        460        470        480 
TLLVGIYFPS VTGIMAGSNR SGDLKDAQKS IPTGTILAIV TTSFIYLSCI VLFGACIEGV 

       490        500        510        520        530        540 
VLRDKFGEAL QGNLVIGMLA WPSPWVIVIG SFFSTCGAGL QSLTGAPRLL QAIARDGIVP 

       550        560        570        580        590        600 
FLQVFGHGKA NGEPTWALLL TVLICETGIL IASLDSVAPI LSMFFLMCYL FVNLACAVQT 

       610        620        630        640        650        660 
LLRTPNWRPR FKFYHWTLSF LGMSLCLALM FICSWYYALS AMLIAGCIYK YIEYRGAEKE 

       670        680        690        700        710        720 
WGDGIRGLSL NAARYALLRV EHGPPHTKNW RPQVLVMLNL DAEQAVKHPR LLSFTSQLKA 

       730        740        750        760        770        780 
GKGLTIVGSV LEGTYLDKHM EAQRAEENIR SLMSTEKTKG FCQLVVSSSL RDGMSHLIQS 

       790        800        810        820        830        840 
AGLGGLKHNT VLMAWPASWK QEDNPFSWKN FVDTVRDTTA AHQALLVAKN VDSFPQNQER 

       850        860        870        880        890        900 
FGGGHIDVWW IVHDGGMLML LPFLLRQHKV WRKCRMRIFT VAQVDDNSIQ MKKDLQMFLY 

       910        920        930        940        950        960 
HLRISAEVEV VEMVENDISA FTYERTLMME QRSQMLKQMQ LSKNEQEREA QLIHDRNTAS 

       970        980        990       1000       1010       1020 
HTAAAARTQA PPTPDKVQMT WTREKLIAEK YRSRDTSLSG FKDLFSMKPD QSNVRRMHTA 

      1030       1040       1050       1060       1070       1080 
VKLNGVVLNK SQDAQLVLLN MPGPPKNRQG DENYMEFLEV LTEGLNRVLL VRGGGREVIT 


IYS 

« Hide

Isoform 2 [UniParc].

Checksum: B70BD65627E6DB4C
Show »

FASTA26628,258

References

« Hide 'large scale' references
[1]"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: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT THR-408.
[2]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Brain and Testis.
[4]"Characterization of long cDNA clones from human adult spleen."
Hattori A., Okumura K., Nagase T., Kikuno R., Hirosawa M., Ohara O.
DNA Res. 7:357-366(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 304-1083 (ISOFORM 1).
Tissue: Spleen.
[5]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 898-1083 (ISOFORM 1).
Tissue: Testis.
[6]"Functional comparison of the K+-Cl- cotransporters KCC1 and KCC4."
Mercado A., Song L., Vazquez N., Mount D.B., Gamba G.
J. Biol. Chem. 275:30326-30334(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-50 AND SER-62, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[9]"Similar Effects of all WNK3 Variants upon SLC12 Cotransporters."
Cruz-Rangel S., Melo Z., Vazquez N., Meade P., Bobadilla N.A., Pasantes-Morales H., Gamba G., Mercado A.
Am. J. Physiol. 301:C601-C608(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF105365 mRNA. Translation: AAD39741.1.
AC116351 Genomic DNA. No translation available.
BC007760 mRNA. Translation: AAH07760.1.
BC098390 mRNA. Translation: AAH98390.1.
AK024493 mRNA. Translation: BAB15783.1.
AK024497 mRNA. Translation: BAB15787.1.
AL117433 mRNA. Translation: CAB55921.1.
CCDSCCDS34129.1. [Q9Y666-1]
PIRT17231.
RefSeqNP_006589.2. NM_006598.2. [Q9Y666-1]
UniGeneHs.172613.

3D structure databases

ProteinModelPortalQ9Y666.
SMRQ9Y666. Positions 411-595.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115947. 1 interaction.
MINTMINT-4658387.
STRING9606.ENSP00000264930.

Chemistry

DrugBankDB00761. Potassium Chloride.
GuidetoPHARMACOLOGY974.

Protein family/group databases

TCDB2.A.30.5.4. the cation-chloride cotransporter (ccc) family.

PTM databases

PhosphoSiteQ9Y666.

Polymorphism databases

DMDM166202480.

Proteomic databases

MaxQBQ9Y666.
PaxDbQ9Y666.
PRIDEQ9Y666.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264930; ENSP00000264930; ENSG00000113504. [Q9Y666-1]
GeneID10723.
KEGGhsa:10723.
UCSCuc003jbu.3. human. [Q9Y666-1]

Organism-specific databases

CTD10723.
GeneCardsGC05M001050.
H-InvDBHIX0004714.
HGNCHGNC:10915. SLC12A7.
HPAHPA041652.
MIM604879. gene.
neXtProtNX_Q9Y666.
PharmGKBPA35809.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0531.
HOGENOMHOG000092644.
HOVERGENHBG052852.
InParanoidQ9Y666.
KOK13627.
OMALIVAMCC.
OrthoDBEOG78M01J.
PhylomeDBQ9Y666.
TreeFamTF313657.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

BgeeQ9Y666.
CleanExHS_SLC12A7.
GenevestigatorQ9Y666.

Family and domain databases

InterProIPR004841. AA-permease/SLC12A_dom.
IPR000076. KCL_cotranspt.
IPR004842. Na/K/Cl_cotransptS.
[Graphical view]
PfamPF00324. AA_permease. 2 hits.
[Graphical view]
PRINTSPR01081. KCLTRNSPORT.
TIGRFAMsTIGR00930. 2a30. 1 hit.
ProtoNetSearch...

Other

ChiTaRSSLC12A7. human.
GeneWikiSLC12A7.
GenomeRNAi10723.
NextBio40705.
PROQ9Y666.
SOURCESearch...

Entry information

Entry nameS12A7_HUMAN
AccessionPrimary (citable) accession number: Q9Y666
Secondary accession number(s): A6NDS8 expand/collapse secondary AC list , Q4G0F3, Q96I81, Q9H7I3, Q9H7I7, Q9UFW2
Entry history
Integrated into UniProtKB/Swiss-Prot: December 13, 2002
Last sequence update: December 4, 2007
Last modified: July 9, 2014
This is version 125 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM