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 7

Gene

SLC12A7

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

Enzyme regulationi

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 WNK3.1 Publication

GO - Molecular functioni

  • potassium:chloride symporter activity Source: ProtInc
  • protein kinase binding Source: ParkinsonsUK-UCL

GO - Biological processi

  • cell volume homeostasis Source: InterPro
  • ion transport Source: Reactome
  • potassium ion transport Source: UniProtKB-KW
  • transmembrane transport Source: Reactome
  • transport Source: ProtInc
Complete GO annotation...

Keywords - Biological processi

Ion transport, Potassium transport, Symport, Transport

Keywords - Ligandi

Potassium

Enzyme and pathway databases

ReactomeiREACT_19315. Cation-coupled Chloride cotransporters.

Protein family/group databases

TCDBi2.A.30.5.4. the cation-chloride cotransporter (ccc) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Solute carrier family 12 member 7
Alternative name(s):
Electroneutral potassium-chloride cotransporter 4
K-Cl cotransporter 4
Gene namesi
Name:SLC12A7
Synonyms:KCC4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:10915. SLC12A7.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 118118CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei119 – 13921HelicalSequence AnalysisAdd
BLAST
Transmembranei141 – 16121HelicalSequence AnalysisAdd
BLAST
Topological domaini162 – 21453CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei215 – 23521HelicalSequence AnalysisAdd
BLAST
Transmembranei253 – 27321HelicalSequence AnalysisAdd
BLAST
Topological domaini274 – 2752CytoplasmicSequence Analysis
Transmembranei276 – 29621HelicalSequence AnalysisAdd
BLAST
Transmembranei416 – 43621HelicalSequence AnalysisAdd
BLAST
Topological domaini437 – 45620CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei457 – 47721HelicalSequence AnalysisAdd
BLAST
Transmembranei494 – 51421HelicalSequence AnalysisAdd
BLAST
Topological domaini515 – 55339CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei554 – 57421HelicalSequence AnalysisAdd
BLAST
Transmembranei578 – 59821HelicalSequence AnalysisAdd
BLAST
Topological domaini599 – 62426CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei625 – 64521HelicalSequence AnalysisAdd
BLAST
Transmembranei845 – 86521HelicalSequence AnalysisAdd
BLAST
Topological domaini866 – 1083218CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA35809.

Chemistry

DrugBankiDB00761. Potassium Chloride.

Polymorphism and mutation databases

BioMutaiSLC12A7.
DMDMi166202480.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10831083Solute carrier family 12 member 7PRO_0000178039Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei30 – 301Phosphothreonine1 Publication
Modified residuei50 – 501Phosphoserine1 Publication
Modified residuei62 – 621Phosphoserine1 Publication
Glycosylationi312 – 3121N-linked (GlcNAc...)Sequence Analysis
Glycosylationi360 – 3601N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ9Y666.
PaxDbiQ9Y666.
PRIDEiQ9Y666.

PTM databases

PhosphoSiteiQ9Y666.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiQ9Y666.
CleanExiHS_SLC12A7.
ExpressionAtlasiQ9Y666. baseline and differential.
GenevisibleiQ9Y666. HS.

Organism-specific databases

HPAiHPA041652.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi115947. 7 interactions.
MINTiMINT-4658387.
STRINGi9606.ENSP00000264930.

Structurei

3D structure databases

ProteinModelPortaliQ9Y666.
SMRiQ9Y666. Positions 411-595.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the SLC12A transporter family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0531.
GeneTreeiENSGT00760000119053.
HOGENOMiHOG000092644.
HOVERGENiHBG052852.
InParanoidiQ9Y666.
KOiK13627.
OMAiLMAWPQS.
OrthoDBiEOG78M01J.
PhylomeDBiQ9Y666.
TreeFamiTF313657.

Family and domain databases

InterProiIPR004841. AA-permease/SLC12A_dom.
IPR030354. KCC4.
IPR000076. KCL_cotranspt.
IPR004842. Na/K/Cl_cotransptS.
[Graphical view]
PANTHERiPTHR11827:SF47. PTHR11827:SF47. 1 hit.
PfamiPF00324. AA_permease. 2 hits.
[Graphical view]
PRINTSiPR01081. KCLTRNSPORT.
TIGRFAMsiTIGR00930. 2a30. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q9Y666-1) [UniParc]FASTAAdd to basket

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
MPTNFTVVPV EAHADGGGDE TAERTEAPGT PEGPEPERPS PGDGNPRENS
60 70 80 90 100
PFLNNVEVEQ ESFFEGKNMA LFEEEMDSNP MVSSLLNKLA NYTNLSQGVV
110 120 130 140 150
EHEEDEESRR REAKAPRMGT FIGVYLPCLQ NILGVILFLR LTWIVGVAGV
160 170 180 190 200
LESFLIVAMC CTCTMLTAIS MSAIATNGVV PAGGSYYMIS RSLGPEFGGA
210 220 230 240 250
VGLCFYLGTT FAGAMYILGT IEIFLTYISP GAAIFQAEAA GGEAAAMLHN
260 270 280 290 300
MRVYGTCTLV LMALVVFVGV KYVNKLALVF LACVVLSILA IYAGVIKSAF
310 320 330 340 350
DPPDIPVCLL GNRTLSRRSF DACVKAYGIH NNSATSALWG LFCNGSQPSA
360 370 380 390 400
ACDEYFIQNN VTEIQGIPGA ASGVFLENLW STYAHAGAFV EKKGVPSVPV
410 420 430 440 450
AEESRASALP YVLTDIAASF TLLVGIYFPS VTGIMAGSNR SGDLKDAQKS
460 470 480 490 500
IPTGTILAIV TTSFIYLSCI VLFGACIEGV VLRDKFGEAL QGNLVIGMLA
510 520 530 540 550
WPSPWVIVIG SFFSTCGAGL QSLTGAPRLL QAIARDGIVP FLQVFGHGKA
560 570 580 590 600
NGEPTWALLL TVLICETGIL IASLDSVAPI LSMFFLMCYL FVNLACAVQT
610 620 630 640 650
LLRTPNWRPR FKFYHWTLSF LGMSLCLALM FICSWYYALS AMLIAGCIYK
660 670 680 690 700
YIEYRGAEKE WGDGIRGLSL NAARYALLRV EHGPPHTKNW RPQVLVMLNL
710 720 730 740 750
DAEQAVKHPR LLSFTSQLKA GKGLTIVGSV LEGTYLDKHM EAQRAEENIR
760 770 780 790 800
SLMSTEKTKG FCQLVVSSSL RDGMSHLIQS AGLGGLKHNT VLMAWPASWK
810 820 830 840 850
QEDNPFSWKN FVDTVRDTTA AHQALLVAKN VDSFPQNQER FGGGHIDVWW
860 870 880 890 900
IVHDGGMLML LPFLLRQHKV WRKCRMRIFT VAQVDDNSIQ MKKDLQMFLY
910 920 930 940 950
HLRISAEVEV VEMVENDISA FTYERTLMME QRSQMLKQMQ LSKNEQEREA
960 970 980 990 1000
QLIHDRNTAS HTAAAARTQA PPTPDKVQMT WTREKLIAEK YRSRDTSLSG
1010 1020 1030 1040 1050
FKDLFSMKPD QSNVRRMHTA VKLNGVVLNK SQDAQLVLLN MPGPPKNRQG
1060 1070 1080
DENYMEFLEV LTEGLNRVLL VRGGGREVIT IYS
Length:1,083
Mass (Da):119,106
Last modified:December 4, 2007 - v3
Checksum:iBF50134614BF6617
GO
Isoform 2 (identifier: Q9Y666-2) [UniParc]FASTAAdd to basket

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.
Show »
Length:266
Mass (Da):28,258
Checksum:iB70BD65627E6DB4C
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti522 – 5221S → T in AAD39741 (PubMed:10347194).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti408 – 4081A → T.1 Publication
Corresponds to variant rs4526148 [ dbSNP | Ensembl ].
VAR_028748

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei227 – 26640YISPG…MALVV → GTEDGVGSLGLGLAQGNRRQ THLSPSDAAQAAHGASYGSF in isoform 2. 1 PublicationVSP_006119Add
BLAST
Alternative sequencei267 – 1083817Missing in isoform 2. 1 PublicationVSP_006120Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS34129.1. [Q9Y666-1]
PIRiT17231.
RefSeqiNP_006589.2. NM_006598.2. [Q9Y666-1]
UniGeneiHs.172613.

Genome annotation databases

EnsembliENST00000264930; ENSP00000264930; ENSG00000113504.
GeneIDi10723.
KEGGihsa:10723.
UCSCiuc003jbu.3. human. [Q9Y666-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS34129.1. [Q9Y666-1]
PIRiT17231.
RefSeqiNP_006589.2. NM_006598.2. [Q9Y666-1]
UniGeneiHs.172613.

3D structure databases

ProteinModelPortaliQ9Y666.
SMRiQ9Y666. Positions 411-595.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115947. 7 interactions.
MINTiMINT-4658387.
STRINGi9606.ENSP00000264930.

Chemistry

DrugBankiDB00761. Potassium Chloride.
GuidetoPHARMACOLOGYi974.

Protein family/group databases

TCDBi2.A.30.5.4. the cation-chloride cotransporter (ccc) family.

PTM databases

PhosphoSiteiQ9Y666.

Polymorphism and mutation databases

BioMutaiSLC12A7.
DMDMi166202480.

Proteomic databases

MaxQBiQ9Y666.
PaxDbiQ9Y666.
PRIDEiQ9Y666.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264930; ENSP00000264930; ENSG00000113504.
GeneIDi10723.
KEGGihsa:10723.
UCSCiuc003jbu.3. human. [Q9Y666-1]

Organism-specific databases

CTDi10723.
GeneCardsiGC05M001050.
H-InvDBHIX0004714.
HGNCiHGNC:10915. SLC12A7.
HPAiHPA041652.
MIMi604879. gene.
neXtProtiNX_Q9Y666.
PharmGKBiPA35809.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0531.
GeneTreeiENSGT00760000119053.
HOGENOMiHOG000092644.
HOVERGENiHBG052852.
InParanoidiQ9Y666.
KOiK13627.
OMAiLMAWPQS.
OrthoDBiEOG78M01J.
PhylomeDBiQ9Y666.
TreeFamiTF313657.

Enzyme and pathway databases

ReactomeiREACT_19315. Cation-coupled Chloride cotransporters.

Miscellaneous databases

ChiTaRSiSLC12A7. human.
GeneWikiiSLC12A7.
GenomeRNAii10723.
NextBioi40705.
PROiQ9Y666.
SOURCEiSearch...

Gene expression databases

BgeeiQ9Y666.
CleanExiHS_SLC12A7.
ExpressionAtlasiQ9Y666. baseline and differential.
GenevisibleiQ9Y666. HS.

Family and domain databases

InterProiIPR004841. AA-permease/SLC12A_dom.
IPR030354. KCC4.
IPR000076. KCL_cotranspt.
IPR004842. Na/K/Cl_cotransptS.
[Graphical view]
PANTHERiPTHR11827:SF47. PTHR11827:SF47. 1 hit.
PfamiPF00324. AA_permease. 2 hits.
[Graphical view]
PRINTSiPR01081. KCLTRNSPORT.
TIGRFAMsiTIGR00930. 2a30. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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. 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. Cited for: ENZYME REGULATION.
  10. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-30, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiS12A7_HUMAN
AccessioniPrimary (citable) accession number: Q9Y666
Secondary accession number(s): A6NDS8
, Q4G0F3, Q96I81, Q9H7I3, Q9H7I7, Q9UFW2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 13, 2002
Last sequence update: December 4, 2007
Last modified: July 22, 2015
This is version 134 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.