Q9Y666 (S12A7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1083 AA.
Sequence status	Complete.
Protein existence	Evidence 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	Membrane; Multi-pass membrane protein.
Tissue specificity	Detected in muscle, brain, lung, heart and kidney.
Sequence similarities	Belongs to the SLC12A transporter family.

Ontologies

Keywords
Biological process	Ion transport Potassium transport Symport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Potassium
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell volume homeostasis Inferred from electronic annotation. Source: Compara potassium ion transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	potassium:chloride symporter activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1083	1083	Solute carrier family 12 member 7		PRO_0000178039
Regions
	Topological domain	1 – 118	118	Cytoplasmic Potential
	Transmembrane	119 – 139	21	Helical; Potential
	Transmembrane	141 – 161	21	Helical; Potential
	Topological domain	162 – 214	53	Cytoplasmic Potential
	Transmembrane	215 – 235	21	Helical; Potential
	Transmembrane	253 – 273	21	Helical; Potential
	Topological domain	274 – 275	2	Cytoplasmic Potential
	Transmembrane	276 – 296	21	Helical; Potential
	Transmembrane	416 – 436	21	Helical; Potential
	Topological domain	437 – 456	20	Cytoplasmic Potential
	Transmembrane	457 – 477	21	Helical; Potential
	Transmembrane	494 – 514	21	Helical; Potential
	Topological domain	515 – 553	39	Cytoplasmic Potential
	Transmembrane	554 – 574	21	Helical; Potential
	Transmembrane	578 – 598	21	Helical; Potential
	Topological domain	599 – 624	26	Cytoplasmic Potential
	Transmembrane	625 – 645	21	Helical; Potential
	Transmembrane	845 – 865	21	Helical; Potential
	Topological domain	866 – 1083	218	Cytoplasmic Potential
Amino acid modifications
	Modified residue	50	1	Phosphoserine Ref.8
	Modified residue	62	1	Phosphoserine Ref.8
	Modified residue	926	1	Phosphothreonine By similarity
	Modified residue	980	1	Phosphothreonine By similarity
	Glycosylation	312	1	N-linked (GlcNAc...) Potential
	Glycosylation	331	1	N-linked (GlcNAc...) Potential
	Glycosylation	344	1	N-linked (GlcNAc...) Potential
	Glycosylation	360	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	227 – 266	40	YISPG…MALVV → GTEDGVGSLGLGLAQGNRRQ THLSPSDAAQAAHGASYGSF in isoform 2.		VSP_006119
	Alternative sequence	267 – 1083	817	Missing in isoform 2.		VSP_006120
	Natural variant	408	1	A → T. Ref.1 Corresponds to variant rs4526148 [ dbSNP | Ensembl ].		VAR_028748
Experimental info
	Sequence conflict	522	1	S → T in AAD39741. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 4, 2007. Version 3. Checksum: BF50134614BF6617	FASTA	1,083	119,106
	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
	Isoform 2 [UniParc]. Checksum: B70BD65627E6DB4C	FASTA	266	28,258
	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 IEIFLTGTED GVGSLGLGLA 250 260 QGNRRQTHLS PSDAAQAAHG ASYGSF

References

	« Hide 'large scale' referencesShow '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. , 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, MASS SPECTROMETRY. 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.
IPI	IPI00008616. IPI00218550.
PIR	T17231.
RefSeq	NP_006589.2. NM_006598.2.
UniGene	Hs.172613.
3D structure databases
ProteinModelPortal	Q9Y666.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000264930.
PTM databases
PhosphoSite	Q9Y666.
Polymorphism databases
DMDM	166202480.
Proteomic databases
PaxDb	Q9Y666.
PRIDE	Q9Y666.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000264930; ENSP00000264930; ENSG00000113504.
GeneID	10723.
KEGG	hsa:10723.
UCSC	uc003jbu.3. human.
Organism-specific databases
CTD	10723.
GeneCards	GC05M001050.
H-InvDB	HIX0004714.
HGNC	HGNC:10915. SLC12A7.
HPA	HPA041652.
MIM	604879. gene.
neXtProt	NX_Q9Y666.
PharmGKB	PA35809.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0531.
HOGENOM	HOG000092644.
HOVERGEN	HBG052852.
InParanoid	Q9Y666.
KO	K13627.
OMA	EDNPFSW.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
Bgee	Q9Y666.
CleanEx	HS_SLC12A7.
Genevestigator	Q9Y666.
GermOnline	ENSG00000113504. Homo sapiens.
Family and domain databases
InterPro	IPR004841. AA-permease_dom. IPR000076. KCL_cotranspt. IPR004842. Na/K/Cl_cotransptS. [Graphical view]
Pfam	PF00324. AA_permease. 2 hits. [Graphical view]
PRINTS	PR01081. KCLTRNSPORT.
TIGRFAMs	TIGR00930. 2a30. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	SLC12A7. human.
DrugBank	DB00761. Potassium Chloride.
GenomeRNAi	10723.
NextBio	40705.
SOURCE	Search...

Entry information

Entry name

S12A7_HUMAN

Accession

Primary (citable) accession number: Q9Y666
Secondary accession number(s): A6NDS8 , Q4G0F3, Q96I81, Q9H7I3, Q9H7I7, Q9UFW2

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 13, 2002
Last sequence update:	December 4, 2007
Last modified:	April 3, 2013
This is version 112 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.