Full text data of SLC12A7
SLC12A7
(KCC4)
[Confidence: high (present in two of the MS resources)]
Solute carrier family 12 member 7 (Electroneutral potassium-chloride cotransporter 4; K-Cl cotransporter 4)
Solute carrier family 12 member 7 (Electroneutral potassium-chloride cotransporter 4; K-Cl cotransporter 4)
hRBCD
IPI00008616
IPI00008616 Splice isoform 1 of Q9Y666 Solute carrier family 12 member 7 Splice isoform 1 of Q9Y666 Solute carrier family 12 member 7 membrane n/a n/a n/a n/a n/a n/a 2 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a integral membrane protein DGIVPFLQVFGHGK, DGMSHLIQSAGLGGLK, DLQMFLYHLR found at its expected molecular weight found at molecular weight
IPI00008616 Splice isoform 1 of Q9Y666 Solute carrier family 12 member 7 Splice isoform 1 of Q9Y666 Solute carrier family 12 member 7 membrane n/a n/a n/a n/a n/a n/a 2 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a integral membrane protein DGIVPFLQVFGHGK, DGMSHLIQSAGLGGLK, DLQMFLYHLR found at its expected molecular weight found at molecular weight
UniProt
Q9Y666
ID S12A7_HUMAN Reviewed; 1083 AA.
AC Q9Y666; A6NDS8; Q4G0F3; Q96I81; Q9H7I3; Q9H7I7; Q9UFW2;
DT 13-DEC-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 04-DEC-2007, sequence version 3.
DT 22-JAN-2014, entry version 120.
DE RecName: Full=Solute carrier family 12 member 7;
DE AltName: Full=Electroneutral potassium-chloride cotransporter 4;
DE AltName: Full=K-Cl cotransporter 4;
GN Name=SLC12A7; Synonyms=KCC4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT THR-408.
RX PubMed=10347194; DOI=10.1074/jbc.274.23.16355;
RA Mount D.B., Mercado A., Song L., Xu J., George A.L. Jr., Delpire E.,
RA Gamba G.;
RT "Cloning and characterization of KCC3 and KCC4, new members of the
RT cation-chloride cotransporter gene family.";
RL J. Biol. Chem. 274:16355-16362(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T.,
RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
RA Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 304-1083 (ISOFORM 1).
RC TISSUE=Spleen;
RX PubMed=11214971; DOI=10.1093/dnares/7.6.357;
RA Hattori A., Okumura K., Nagase T., Kikuno R., Hirosawa M., Ohara O.;
RT "Characterization of long cDNA clones from human adult spleen.";
RL DNA Res. 7:357-366(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 898-1083 (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP FUNCTION.
RX PubMed=10913127; DOI=10.1074/jbc.M003112200;
RA Mercado A., Song L., Vazquez N., Mount D.B., Gamba G.;
RT "Functional comparison of the K+-Cl- cotransporters KCC1 and KCC4.";
RL J. Biol. Chem. 275:30326-30334(2000).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-50 AND SER-62, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [9]
RP ENZYME REGULATION.
RX PubMed=21613606; DOI=10.1152/ajpcell.00070.2011;
RA Cruz-Rangel S., Melo Z., Vazquez N., Meade P., Bobadilla N.A.,
RA Pasantes-Morales H., Gamba G., Mercado A.;
RT "Similar Effects of all WNK3 Variants upon SLC12 Cotransporters.";
RL Am. J. Physiol. 301:C601-C608(2011).
CC -!- FUNCTION: Mediates electroneutral potassium-chloride cotransport
CC when activated by cell swelling. May mediate K(+) uptake into
CC Deiters' cells in the cochlea and contribute to K(+) recycling in
CC the inner ear. Important for the survival of cochlear outer and
CC inner hair cells and the maintenance of the organ of Corti. May be
CC required for basolateral Cl(-) extrusion in the kidney and
CC contribute to renal acidification (By similarity).
CC -!- ENZYME REGULATION: Activated by N-ethylmaleimide (NEM). Inhibited
CC by furosemide, DIDS and bumetanide. The inhibition is much
CC stronger in the presence of 50 mM K(+) in the uptake medium.
CC Inhibited by DIOA. Inhibited by WNK3.
CC -!- SUBUNIT: Homomultimer and heteromultimer with other K-Cl
CC cotransporters (By similarity).
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y666-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y666-2; Sequence=VSP_006119, VSP_006120;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Detected in muscle, brain, lung, heart and
CC kidney.
CC -!- SIMILARITY: Belongs to the SLC12A transporter family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF105365; AAD39741.1; -; mRNA.
DR EMBL; AC116351; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC007760; AAH07760.1; -; mRNA.
DR EMBL; BC098390; AAH98390.1; -; mRNA.
DR EMBL; AK024493; BAB15783.1; -; mRNA.
DR EMBL; AK024497; BAB15787.1; -; mRNA.
DR EMBL; AL117433; CAB55921.1; -; mRNA.
DR PIR; T17231; T17231.
DR RefSeq; NP_006589.2; NM_006598.2.
DR UniGene; Hs.172613; -.
DR ProteinModelPortal; Q9Y666; -.
DR SMR; Q9Y666; 411-595.
DR MINT; MINT-4658387; -.
DR STRING; 9606.ENSP00000264930; -.
DR DrugBank; DB00761; Potassium Chloride.
DR GuidetoPHARMACOLOGY; 974; -.
DR TCDB; 2.A.30.5.4; the cation-chloride cotransporter (ccc) family.
DR PhosphoSite; Q9Y666; -.
DR DMDM; 166202480; -.
DR PaxDb; Q9Y666; -.
DR PRIDE; Q9Y666; -.
DR Ensembl; ENST00000264930; ENSP00000264930; ENSG00000113504.
DR GeneID; 10723; -.
DR KEGG; hsa:10723; -.
DR UCSC; uc003jbu.3; human.
DR CTD; 10723; -.
DR GeneCards; GC05M001050; -.
DR H-InvDB; HIX0004714; -.
DR HGNC; HGNC:10915; SLC12A7.
DR HPA; HPA041652; -.
DR MIM; 604879; gene.
DR neXtProt; NX_Q9Y666; -.
DR PharmGKB; PA35809; -.
DR eggNOG; COG0531; -.
DR HOGENOM; HOG000092644; -.
DR HOVERGEN; HBG052852; -.
DR InParanoid; Q9Y666; -.
DR KO; K13627; -.
DR OMA; MLNLDAE; -.
DR OrthoDB; EOG78M01J; -.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR ChiTaRS; SLC12A7; human.
DR GeneWiki; SLC12A7; -.
DR GenomeRNAi; 10723; -.
DR NextBio; 40705; -.
DR PRO; PR:Q9Y666; -.
DR Bgee; Q9Y666; -.
DR CleanEx; HS_SLC12A7; -.
DR Genevestigator; Q9Y666; -.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR GO; GO:0015379; F:potassium:chloride symporter activity; TAS:ProtInc.
DR GO; GO:0006884; P:cell volume homeostasis; IEA:Ensembl.
DR GO; GO:0006813; P:potassium ion transport; IEA:UniProtKB-KW.
DR InterPro; IPR004841; AA-permease/SLC12A_dom.
DR InterPro; IPR000076; KCL_cotranspt.
DR InterPro; IPR004842; Na/K/Cl_cotransptS.
DR Pfam; PF00324; AA_permease; 2.
DR PRINTS; PR01081; KCLTRNSPORT.
DR TIGRFAMs; TIGR00930; 2a30; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Complete proteome; Glycoprotein;
KW Ion transport; Membrane; Phosphoprotein; Polymorphism; Potassium;
KW Potassium transport; Reference proteome; Symport; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1 1083 Solute carrier family 12 member 7.
FT /FTId=PRO_0000178039.
FT TOPO_DOM 1 118 Cytoplasmic (Potential).
FT TRANSMEM 119 139 Helical; (Potential).
FT TRANSMEM 141 161 Helical; (Potential).
FT TOPO_DOM 162 214 Cytoplasmic (Potential).
FT TRANSMEM 215 235 Helical; (Potential).
FT TRANSMEM 253 273 Helical; (Potential).
FT TOPO_DOM 274 275 Cytoplasmic (Potential).
FT TRANSMEM 276 296 Helical; (Potential).
FT TRANSMEM 416 436 Helical; (Potential).
FT TOPO_DOM 437 456 Cytoplasmic (Potential).
FT TRANSMEM 457 477 Helical; (Potential).
FT TRANSMEM 494 514 Helical; (Potential).
FT TOPO_DOM 515 553 Cytoplasmic (Potential).
FT TRANSMEM 554 574 Helical; (Potential).
FT TRANSMEM 578 598 Helical; (Potential).
FT TOPO_DOM 599 624 Cytoplasmic (Potential).
FT TRANSMEM 625 645 Helical; (Potential).
FT TRANSMEM 845 865 Helical; (Potential).
FT TOPO_DOM 866 1083 Cytoplasmic (Potential).
FT MOD_RES 50 50 Phosphoserine.
FT MOD_RES 62 62 Phosphoserine.
FT CARBOHYD 312 312 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 360 360 N-linked (GlcNAc...) (Potential).
FT VAR_SEQ 227 266 YISPGAAIFQAEAAGGEAAAMLHNMRVYGTCTLVLMALVV
FT -> GTEDGVGSLGLGLAQGNRRQTHLSPSDAAQAAHGASYG
FT SF (in isoform 2).
FT /FTId=VSP_006119.
FT VAR_SEQ 267 1083 Missing (in isoform 2).
FT /FTId=VSP_006120.
FT VARIANT 408 408 A -> T (in dbSNP:rs4526148).
FT /FTId=VAR_028748.
FT CONFLICT 522 522 S -> T (in Ref. 1; AAD39741).
SQ SEQUENCE 1083 AA; 119106 MW; BF50134614BF6617 CRC64;
MPTNFTVVPV EAHADGGGDE TAERTEAPGT PEGPEPERPS PGDGNPRENS PFLNNVEVEQ
ESFFEGKNMA LFEEEMDSNP MVSSLLNKLA NYTNLSQGVV EHEEDEESRR REAKAPRMGT
FIGVYLPCLQ NILGVILFLR LTWIVGVAGV LESFLIVAMC CTCTMLTAIS MSAIATNGVV
PAGGSYYMIS RSLGPEFGGA VGLCFYLGTT FAGAMYILGT IEIFLTYISP GAAIFQAEAA
GGEAAAMLHN MRVYGTCTLV LMALVVFVGV KYVNKLALVF LACVVLSILA IYAGVIKSAF
DPPDIPVCLL GNRTLSRRSF DACVKAYGIH NNSATSALWG LFCNGSQPSA ACDEYFIQNN
VTEIQGIPGA ASGVFLENLW STYAHAGAFV EKKGVPSVPV AEESRASALP YVLTDIAASF
TLLVGIYFPS VTGIMAGSNR SGDLKDAQKS IPTGTILAIV TTSFIYLSCI VLFGACIEGV
VLRDKFGEAL QGNLVIGMLA WPSPWVIVIG SFFSTCGAGL QSLTGAPRLL QAIARDGIVP
FLQVFGHGKA NGEPTWALLL TVLICETGIL IASLDSVAPI LSMFFLMCYL FVNLACAVQT
LLRTPNWRPR FKFYHWTLSF LGMSLCLALM FICSWYYALS AMLIAGCIYK YIEYRGAEKE
WGDGIRGLSL NAARYALLRV EHGPPHTKNW RPQVLVMLNL DAEQAVKHPR LLSFTSQLKA
GKGLTIVGSV LEGTYLDKHM EAQRAEENIR SLMSTEKTKG FCQLVVSSSL RDGMSHLIQS
AGLGGLKHNT VLMAWPASWK QEDNPFSWKN FVDTVRDTTA AHQALLVAKN VDSFPQNQER
FGGGHIDVWW IVHDGGMLML LPFLLRQHKV WRKCRMRIFT VAQVDDNSIQ MKKDLQMFLY
HLRISAEVEV VEMVENDISA FTYERTLMME QRSQMLKQMQ LSKNEQEREA QLIHDRNTAS
HTAAAARTQA PPTPDKVQMT WTREKLIAEK YRSRDTSLSG FKDLFSMKPD QSNVRRMHTA
VKLNGVVLNK SQDAQLVLLN MPGPPKNRQG DENYMEFLEV LTEGLNRVLL VRGGGREVIT
IYS
//
ID S12A7_HUMAN Reviewed; 1083 AA.
AC Q9Y666; A6NDS8; Q4G0F3; Q96I81; Q9H7I3; Q9H7I7; Q9UFW2;
DT 13-DEC-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 04-DEC-2007, sequence version 3.
DT 22-JAN-2014, entry version 120.
DE RecName: Full=Solute carrier family 12 member 7;
DE AltName: Full=Electroneutral potassium-chloride cotransporter 4;
DE AltName: Full=K-Cl cotransporter 4;
GN Name=SLC12A7; Synonyms=KCC4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT THR-408.
RX PubMed=10347194; DOI=10.1074/jbc.274.23.16355;
RA Mount D.B., Mercado A., Song L., Xu J., George A.L. Jr., Delpire E.,
RA Gamba G.;
RT "Cloning and characterization of KCC3 and KCC4, new members of the
RT cation-chloride cotransporter gene family.";
RL J. Biol. Chem. 274:16355-16362(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T.,
RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
RA Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 304-1083 (ISOFORM 1).
RC TISSUE=Spleen;
RX PubMed=11214971; DOI=10.1093/dnares/7.6.357;
RA Hattori A., Okumura K., Nagase T., Kikuno R., Hirosawa M., Ohara O.;
RT "Characterization of long cDNA clones from human adult spleen.";
RL DNA Res. 7:357-366(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 898-1083 (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP FUNCTION.
RX PubMed=10913127; DOI=10.1074/jbc.M003112200;
RA Mercado A., Song L., Vazquez N., Mount D.B., Gamba G.;
RT "Functional comparison of the K+-Cl- cotransporters KCC1 and KCC4.";
RL J. Biol. Chem. 275:30326-30334(2000).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-50 AND SER-62, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [9]
RP ENZYME REGULATION.
RX PubMed=21613606; DOI=10.1152/ajpcell.00070.2011;
RA Cruz-Rangel S., Melo Z., Vazquez N., Meade P., Bobadilla N.A.,
RA Pasantes-Morales H., Gamba G., Mercado A.;
RT "Similar Effects of all WNK3 Variants upon SLC12 Cotransporters.";
RL Am. J. Physiol. 301:C601-C608(2011).
CC -!- FUNCTION: Mediates electroneutral potassium-chloride cotransport
CC when activated by cell swelling. May mediate K(+) uptake into
CC Deiters' cells in the cochlea and contribute to K(+) recycling in
CC the inner ear. Important for the survival of cochlear outer and
CC inner hair cells and the maintenance of the organ of Corti. May be
CC required for basolateral Cl(-) extrusion in the kidney and
CC contribute to renal acidification (By similarity).
CC -!- ENZYME REGULATION: Activated by N-ethylmaleimide (NEM). Inhibited
CC by furosemide, DIDS and bumetanide. The inhibition is much
CC stronger in the presence of 50 mM K(+) in the uptake medium.
CC Inhibited by DIOA. Inhibited by WNK3.
CC -!- SUBUNIT: Homomultimer and heteromultimer with other K-Cl
CC cotransporters (By similarity).
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y666-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y666-2; Sequence=VSP_006119, VSP_006120;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Detected in muscle, brain, lung, heart and
CC kidney.
CC -!- SIMILARITY: Belongs to the SLC12A transporter family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF105365; AAD39741.1; -; mRNA.
DR EMBL; AC116351; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC007760; AAH07760.1; -; mRNA.
DR EMBL; BC098390; AAH98390.1; -; mRNA.
DR EMBL; AK024493; BAB15783.1; -; mRNA.
DR EMBL; AK024497; BAB15787.1; -; mRNA.
DR EMBL; AL117433; CAB55921.1; -; mRNA.
DR PIR; T17231; T17231.
DR RefSeq; NP_006589.2; NM_006598.2.
DR UniGene; Hs.172613; -.
DR ProteinModelPortal; Q9Y666; -.
DR SMR; Q9Y666; 411-595.
DR MINT; MINT-4658387; -.
DR STRING; 9606.ENSP00000264930; -.
DR DrugBank; DB00761; Potassium Chloride.
DR GuidetoPHARMACOLOGY; 974; -.
DR TCDB; 2.A.30.5.4; the cation-chloride cotransporter (ccc) family.
DR PhosphoSite; Q9Y666; -.
DR DMDM; 166202480; -.
DR PaxDb; Q9Y666; -.
DR PRIDE; Q9Y666; -.
DR Ensembl; ENST00000264930; ENSP00000264930; ENSG00000113504.
DR GeneID; 10723; -.
DR KEGG; hsa:10723; -.
DR UCSC; uc003jbu.3; human.
DR CTD; 10723; -.
DR GeneCards; GC05M001050; -.
DR H-InvDB; HIX0004714; -.
DR HGNC; HGNC:10915; SLC12A7.
DR HPA; HPA041652; -.
DR MIM; 604879; gene.
DR neXtProt; NX_Q9Y666; -.
DR PharmGKB; PA35809; -.
DR eggNOG; COG0531; -.
DR HOGENOM; HOG000092644; -.
DR HOVERGEN; HBG052852; -.
DR InParanoid; Q9Y666; -.
DR KO; K13627; -.
DR OMA; MLNLDAE; -.
DR OrthoDB; EOG78M01J; -.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR ChiTaRS; SLC12A7; human.
DR GeneWiki; SLC12A7; -.
DR GenomeRNAi; 10723; -.
DR NextBio; 40705; -.
DR PRO; PR:Q9Y666; -.
DR Bgee; Q9Y666; -.
DR CleanEx; HS_SLC12A7; -.
DR Genevestigator; Q9Y666; -.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR GO; GO:0015379; F:potassium:chloride symporter activity; TAS:ProtInc.
DR GO; GO:0006884; P:cell volume homeostasis; IEA:Ensembl.
DR GO; GO:0006813; P:potassium ion transport; IEA:UniProtKB-KW.
DR InterPro; IPR004841; AA-permease/SLC12A_dom.
DR InterPro; IPR000076; KCL_cotranspt.
DR InterPro; IPR004842; Na/K/Cl_cotransptS.
DR Pfam; PF00324; AA_permease; 2.
DR PRINTS; PR01081; KCLTRNSPORT.
DR TIGRFAMs; TIGR00930; 2a30; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Complete proteome; Glycoprotein;
KW Ion transport; Membrane; Phosphoprotein; Polymorphism; Potassium;
KW Potassium transport; Reference proteome; Symport; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1 1083 Solute carrier family 12 member 7.
FT /FTId=PRO_0000178039.
FT TOPO_DOM 1 118 Cytoplasmic (Potential).
FT TRANSMEM 119 139 Helical; (Potential).
FT TRANSMEM 141 161 Helical; (Potential).
FT TOPO_DOM 162 214 Cytoplasmic (Potential).
FT TRANSMEM 215 235 Helical; (Potential).
FT TRANSMEM 253 273 Helical; (Potential).
FT TOPO_DOM 274 275 Cytoplasmic (Potential).
FT TRANSMEM 276 296 Helical; (Potential).
FT TRANSMEM 416 436 Helical; (Potential).
FT TOPO_DOM 437 456 Cytoplasmic (Potential).
FT TRANSMEM 457 477 Helical; (Potential).
FT TRANSMEM 494 514 Helical; (Potential).
FT TOPO_DOM 515 553 Cytoplasmic (Potential).
FT TRANSMEM 554 574 Helical; (Potential).
FT TRANSMEM 578 598 Helical; (Potential).
FT TOPO_DOM 599 624 Cytoplasmic (Potential).
FT TRANSMEM 625 645 Helical; (Potential).
FT TRANSMEM 845 865 Helical; (Potential).
FT TOPO_DOM 866 1083 Cytoplasmic (Potential).
FT MOD_RES 50 50 Phosphoserine.
FT MOD_RES 62 62 Phosphoserine.
FT CARBOHYD 312 312 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 360 360 N-linked (GlcNAc...) (Potential).
FT VAR_SEQ 227 266 YISPGAAIFQAEAAGGEAAAMLHNMRVYGTCTLVLMALVV
FT -> GTEDGVGSLGLGLAQGNRRQTHLSPSDAAQAAHGASYG
FT SF (in isoform 2).
FT /FTId=VSP_006119.
FT VAR_SEQ 267 1083 Missing (in isoform 2).
FT /FTId=VSP_006120.
FT VARIANT 408 408 A -> T (in dbSNP:rs4526148).
FT /FTId=VAR_028748.
FT CONFLICT 522 522 S -> T (in Ref. 1; AAD39741).
SQ SEQUENCE 1083 AA; 119106 MW; BF50134614BF6617 CRC64;
MPTNFTVVPV EAHADGGGDE TAERTEAPGT PEGPEPERPS PGDGNPRENS PFLNNVEVEQ
ESFFEGKNMA LFEEEMDSNP MVSSLLNKLA NYTNLSQGVV EHEEDEESRR REAKAPRMGT
FIGVYLPCLQ NILGVILFLR LTWIVGVAGV LESFLIVAMC CTCTMLTAIS MSAIATNGVV
PAGGSYYMIS RSLGPEFGGA VGLCFYLGTT FAGAMYILGT IEIFLTYISP GAAIFQAEAA
GGEAAAMLHN MRVYGTCTLV LMALVVFVGV KYVNKLALVF LACVVLSILA IYAGVIKSAF
DPPDIPVCLL GNRTLSRRSF DACVKAYGIH NNSATSALWG LFCNGSQPSA ACDEYFIQNN
VTEIQGIPGA ASGVFLENLW STYAHAGAFV EKKGVPSVPV AEESRASALP YVLTDIAASF
TLLVGIYFPS VTGIMAGSNR SGDLKDAQKS IPTGTILAIV TTSFIYLSCI VLFGACIEGV
VLRDKFGEAL QGNLVIGMLA WPSPWVIVIG SFFSTCGAGL QSLTGAPRLL QAIARDGIVP
FLQVFGHGKA NGEPTWALLL TVLICETGIL IASLDSVAPI LSMFFLMCYL FVNLACAVQT
LLRTPNWRPR FKFYHWTLSF LGMSLCLALM FICSWYYALS AMLIAGCIYK YIEYRGAEKE
WGDGIRGLSL NAARYALLRV EHGPPHTKNW RPQVLVMLNL DAEQAVKHPR LLSFTSQLKA
GKGLTIVGSV LEGTYLDKHM EAQRAEENIR SLMSTEKTKG FCQLVVSSSL RDGMSHLIQS
AGLGGLKHNT VLMAWPASWK QEDNPFSWKN FVDTVRDTTA AHQALLVAKN VDSFPQNQER
FGGGHIDVWW IVHDGGMLML LPFLLRQHKV WRKCRMRIFT VAQVDDNSIQ MKKDLQMFLY
HLRISAEVEV VEMVENDISA FTYERTLMME QRSQMLKQMQ LSKNEQEREA QLIHDRNTAS
HTAAAARTQA PPTPDKVQMT WTREKLIAEK YRSRDTSLSG FKDLFSMKPD QSNVRRMHTA
VKLNGVVLNK SQDAQLVLLN MPGPPKNRQG DENYMEFLEV LTEGLNRVLL VRGGGREVIT
IYS
//
MIM
604879
*RECORD*
*FIELD* NO
604879
*FIELD* TI
*604879 SOLUTE CARRIER FAMILY 12 (POTASSIUM/CHLORIDE TRANSPORTER), MEMBER
7; SLC12A7
read more;;POTASSIUM-CHLORIDE COTRANSPORTER 4; KCC4
*FIELD* TX
Cation chloride cotransporters, including the potassium-chloride
cotransporters (KCCs), are involved in the electroneutral movement of
ions across the plasma membrane. Under most physiologic conditions, KCCs
function as efflux pathways (Mount et al., 1999).
CLONING
By searching EST databases, Mount et al. (1999) identified a cDNA
encoding SLC12A7, which they initially termed KCC3 but later renamed
KCC4. The deduced 1,083-amino acid SLC12A7 protein contains 12
membrane-spanning segments, 8 phosphorylation sites, 7 of which are in
the C terminus, and 4 potential N-glycosylation sites. SLC12A7 shares
65% amino acid identity with SLC12A4 (604119) and 66% identity with
SLC12A6 (604878). Northern blot analysis detected a 5.3-kb SLC12A7
transcript in most tissues tested, with highest expression in heart and
kidney and little or no expression in adult brain. Functional analysis
confirmed that SLC12A7 is a KCC.
MAPPING
By radiation hybrid and somatic cell hybrid analyses, Mount et al.
(1999) mapped the SLC12A7 gene, which contains marker D5S110, to 5p15.3.
ANIMAL MODEL
Boettger et al. (2002) generated mice constitutively lacking KCC4, which
is predominantly expressed in kidney, heart, lung, and liver. Kcc4 -/-
mice were born at the expected mendelian ratio. They were viable and
fertile; however, their body weight was roughly 90% that of their
littermates. Mice had normal hearing loss at postnatal day 14, indicated
by normal auditory brainstem responses. Hearing deteriorated quickly
during the following week, after which mice were nearly deaf, with a
hearing loss of 70 to 80 decibels. Histologic analysis revealed that the
inner ear developed normally and could not be distinguished from those
of wildtype animals at postnatal day 14. At postnatal day 21, however,
outer hair cells of basal turns of the cochlea were almost totally
absent, whereas inner hair cells were still present. The degeneration
proceeded from basal to apical turns. In adult knockout mice, the organ
of Corti was lost completely in basal turns. In apical turns, some hair
cells survived, accounting for the residual hearing ability in adult
mice. Even in adult mice, there was no collapse of the Reissner
membrane, which separates the scala media from the scala vestibuli,
suggesting that Kcc4 is not essential for endolymph production. Outer
hair cells of Kcc4 -/- mice degenerated before Deiters cells were lost,
although Deiters cells and not outer hair cells normally express Kcc4 at
this stage. This is consistent with a disturbance of extracellular
homeostasis due to impaired salt uptake by Deiters cells, and may lead
to death of outer hair cells by osmotic stress or membrane
depolarization. Deafness in Kcc4 -/- mice was associated with renal
tubular acidosis. The urine of knockout mice was more alkaline than that
of wildtype littermates, whereas concentrations of sodium, potassium,
and chloride were not changed. Blood gas analysis indicated a
compensated metabolic acidosis with significantly decreased base excess.
Immunofluorescence revealed that Kcc4 is expressed in basolateral
membranes of several nephron segments. Intracellular chloride
concentration was increased in proximal tubules and particularly in
alpha-intercalated cells of knockout mice. Considering the prominent
chloride/bicarbonate exchange activity in alpha-intercalated cells, the
rise in intracellular chloride predicts a more alkaline intracellular pH
in the knockout mice. This will decrease apical proton secretion by
increasing the electrochemical gradient against which pumping has to
occur. Thus, KCC4 joins the hydrogen ATPase (192132) and AE1 anion
exchanger (109270) as the third transport protein of alpha-intercalated
cells whose mutation entails renal tubular acidosis. Boettger et al.
(2002) concluded that KCC4 is important for potassium recycling by
siphoning potassium ions after their exit from outer hair cells into
supporting Deiters cells, where potassium enters the gap junction
pathway.
*FIELD* RF
1. Boettger, T.; Hubner, C. A.; Maler, H.; Rust, M. B.; Beck, F. X.;
Jentsch, T. J.: Deafness and renal tubular acidosis in mice lacking
the K-CI co-transporter Kcc4. Nature 416: 874-878, 2002.
2. Mount, D. B.; Mercado, A.; Song, L.; Xu, J.; George, A. L., Jr.;
Delpire, E.; Gamba, G.: Cloning and characterization of KCC3 and
KCC4, new members of the cation-chloride cotransporter gene family. J.
Biol. Chem. 274: 16355-16362, 1999.
*FIELD* CN
Ada Hamosh - updated: 5/8/2002
*FIELD* CD
Paul J. Converse: 4/26/2000
*FIELD* ED
wwang: 08/02/2007
cwells: 11/12/2003
alopez: 5/9/2002
terry: 5/8/2002
mgross: 4/26/2000
*RECORD*
*FIELD* NO
604879
*FIELD* TI
*604879 SOLUTE CARRIER FAMILY 12 (POTASSIUM/CHLORIDE TRANSPORTER), MEMBER
7; SLC12A7
read more;;POTASSIUM-CHLORIDE COTRANSPORTER 4; KCC4
*FIELD* TX
Cation chloride cotransporters, including the potassium-chloride
cotransporters (KCCs), are involved in the electroneutral movement of
ions across the plasma membrane. Under most physiologic conditions, KCCs
function as efflux pathways (Mount et al., 1999).
CLONING
By searching EST databases, Mount et al. (1999) identified a cDNA
encoding SLC12A7, which they initially termed KCC3 but later renamed
KCC4. The deduced 1,083-amino acid SLC12A7 protein contains 12
membrane-spanning segments, 8 phosphorylation sites, 7 of which are in
the C terminus, and 4 potential N-glycosylation sites. SLC12A7 shares
65% amino acid identity with SLC12A4 (604119) and 66% identity with
SLC12A6 (604878). Northern blot analysis detected a 5.3-kb SLC12A7
transcript in most tissues tested, with highest expression in heart and
kidney and little or no expression in adult brain. Functional analysis
confirmed that SLC12A7 is a KCC.
MAPPING
By radiation hybrid and somatic cell hybrid analyses, Mount et al.
(1999) mapped the SLC12A7 gene, which contains marker D5S110, to 5p15.3.
ANIMAL MODEL
Boettger et al. (2002) generated mice constitutively lacking KCC4, which
is predominantly expressed in kidney, heart, lung, and liver. Kcc4 -/-
mice were born at the expected mendelian ratio. They were viable and
fertile; however, their body weight was roughly 90% that of their
littermates. Mice had normal hearing loss at postnatal day 14, indicated
by normal auditory brainstem responses. Hearing deteriorated quickly
during the following week, after which mice were nearly deaf, with a
hearing loss of 70 to 80 decibels. Histologic analysis revealed that the
inner ear developed normally and could not be distinguished from those
of wildtype animals at postnatal day 14. At postnatal day 21, however,
outer hair cells of basal turns of the cochlea were almost totally
absent, whereas inner hair cells were still present. The degeneration
proceeded from basal to apical turns. In adult knockout mice, the organ
of Corti was lost completely in basal turns. In apical turns, some hair
cells survived, accounting for the residual hearing ability in adult
mice. Even in adult mice, there was no collapse of the Reissner
membrane, which separates the scala media from the scala vestibuli,
suggesting that Kcc4 is not essential for endolymph production. Outer
hair cells of Kcc4 -/- mice degenerated before Deiters cells were lost,
although Deiters cells and not outer hair cells normally express Kcc4 at
this stage. This is consistent with a disturbance of extracellular
homeostasis due to impaired salt uptake by Deiters cells, and may lead
to death of outer hair cells by osmotic stress or membrane
depolarization. Deafness in Kcc4 -/- mice was associated with renal
tubular acidosis. The urine of knockout mice was more alkaline than that
of wildtype littermates, whereas concentrations of sodium, potassium,
and chloride were not changed. Blood gas analysis indicated a
compensated metabolic acidosis with significantly decreased base excess.
Immunofluorescence revealed that Kcc4 is expressed in basolateral
membranes of several nephron segments. Intracellular chloride
concentration was increased in proximal tubules and particularly in
alpha-intercalated cells of knockout mice. Considering the prominent
chloride/bicarbonate exchange activity in alpha-intercalated cells, the
rise in intracellular chloride predicts a more alkaline intracellular pH
in the knockout mice. This will decrease apical proton secretion by
increasing the electrochemical gradient against which pumping has to
occur. Thus, KCC4 joins the hydrogen ATPase (192132) and AE1 anion
exchanger (109270) as the third transport protein of alpha-intercalated
cells whose mutation entails renal tubular acidosis. Boettger et al.
(2002) concluded that KCC4 is important for potassium recycling by
siphoning potassium ions after their exit from outer hair cells into
supporting Deiters cells, where potassium enters the gap junction
pathway.
*FIELD* RF
1. Boettger, T.; Hubner, C. A.; Maler, H.; Rust, M. B.; Beck, F. X.;
Jentsch, T. J.: Deafness and renal tubular acidosis in mice lacking
the K-CI co-transporter Kcc4. Nature 416: 874-878, 2002.
2. Mount, D. B.; Mercado, A.; Song, L.; Xu, J.; George, A. L., Jr.;
Delpire, E.; Gamba, G.: Cloning and characterization of KCC3 and
KCC4, new members of the cation-chloride cotransporter gene family. J.
Biol. Chem. 274: 16355-16362, 1999.
*FIELD* CN
Ada Hamosh - updated: 5/8/2002
*FIELD* CD
Paul J. Converse: 4/26/2000
*FIELD* ED
wwang: 08/02/2007
cwells: 11/12/2003
alopez: 5/9/2002
terry: 5/8/2002
mgross: 4/26/2000