Q9WVL3 (S12A7_MOUSE) 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

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

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 By similarity. 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. Ref.5
Enzyme regulation	Inhibited by WNK3 By similarity.
Subunit structure	Homomultimer and heteromultimer with other K-Cl cotransporters Probable. Ref.4
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Detected in proximal tubules in the kidney, in particular in basolateral membranes of intercalated cells in the cortical collecting duct.
Developmental stage	In 8 day old mice, before the onset of hearing, detected in membranes of the stria vascularis and in most cells of the organ of Corti. At P14, when the organ of Corti has matured, expression is no longer detected in hair cells and the stria, but is restricted to Deiters' cells that are supporting outer hair cells and to phalangeal cells enveloping the inner hair cells.
Involvement in disease	Defects in Slc12a7 are a cause of deafness due to the progressive degeneration of outer and inner hair cells in the cochlea and of neurons in the cochlear ganglion, leading to the loss of the organ of Corti. Ref.5
Sequence similarities	Belongs to the SLC12A transporter family.
Sequence caution	The sequence BAD21379.1 differs from that shown. Reason: Erroneous initiation. The sequence BAE42491.1 differs from that shown. Reason: Frameshift at position 32.

Ontologies

Keywords
Biological process	Ion transport Potassium transport Symport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Disease	Deafness
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 membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	potassium:chloride symporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9WVL3-1)

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: Q9WVL3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1010-1080: DQSNVRRMHT...VRGGGREVIT → LLHFMLFENR...GLTGATETHL

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_0000178040
Regions
	Topological domain	1 – 118	118	Cytoplasmic Potential
	Transmembrane	119 – 139	21	Helical; Potential
	Transmembrane	141 – 161	21	Helical; Potential
	Topological domain	162 – 200	39	Cytoplasmic Potential
	Transmembrane	201 – 221	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	37	1	Phosphothreonine Ref.6
	Modified residue	50	1	Phosphoserine Ref.6
	Modified residue	62	1	Phosphoserine By similarity
	Modified residue	926	1	Phosphothreonine Ref.6
	Modified residue	980	1	Phosphothreonine Ref.6
	Glycosylation	312	1	N-linked (GlcNAc...) Potential
	Glycosylation	331	1	N-linked (GlcNAc...) Ref.7 Ref.8
	Glycosylation	344	1	N-linked (GlcNAc...) Potential
	Glycosylation	360	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1010 – 1080	71	DQSNV…REVIT → LLHFMLFENRCWTKHTVIVP FPWSEFRVPVMKGLTGATET HL in isoform 2.		VSP_027770
Experimental info
	Sequence conflict	40	1	T → M in BAE41477. Ref.3
	Sequence conflict	355	1	Y → F in BAE41477. Ref.3
	Sequence conflict	951	1	Q → P in BAE29061. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: E339D43F7D3B6BD7	FASTA	1,083	119,481
	10 20 30 40 50 60 MPTNFTVVPV EARADGAGDE AAERTEEPES PESVDQTSPT PGDGNPRENS PFINNVEVER 70 80 90 100 110 120 ESYFEGKNMA LFEEEMDSNP MVSSLLNKLA NYTNLSQGVV EHEEDEDSRR REVKAPRMGT 130 140 150 160 170 180 FIGVYLPCLQ NILGVILFLR LTWIVGAAGV MESFLIVAMC CTCTMLTAIS MSAIATNGVV 190 200 210 220 230 240 PAGGSYYMIS RSLGPEFGGA VGLCFYLGTT FAGAMYILGT IEIFLTYISP SAAIFQAETA 250 260 270 280 290 300 DGEAAALLNN MRVYGSCALA LMAVVVFVGV KYVNKLALVF LACVVLSILA IYAGVIKTAF 310 320 330 340 350 360 APPDIPVCLL GNRTLANRNF DTCAKMQVVS NGTVTTALWR LFCNGSSLGA TCDEYFAQNN 370 380 390 400 410 420 VTEIQGIPGV ASGVFLDNLW STYSDKGAFV EKKGVSSVPV SEESRPGGLP YVLTDIMTYF 430 440 450 460 470 480 TMLVGIYFPS VTGIMAGSNR SGDLKDAQKS IPTGTILAIV TTSFIYLSCI VLFGACIEGV 490 500 510 520 530 540 VLRDKFGEAL QGNLVIGMLA WPSPWVIVIG SFFSTCGAGL QSLTGAPRLL QAIARDGIIP 550 560 570 580 590 600 FLQVFGHGKA NGEPTWALLL TALICETGIL IASLDSVAPI LSMFFLMCYM FVNLACAVQT 610 620 630 640 650 660 LLRTPNWRPR FKFYHWTLSF LGMSLCLALM FICSWYYALF AMLIAGCIYK YIEYRGAEKE 670 680 690 700 710 720 WGDGIRGLSL NAARYALLRV EHGPPHTKNW RPQVLVMLNL DSEQCVKHPR LLSFTSQLKA 730 740 750 760 770 780 GKGLTIVGSV LEGTYLDKHV EAQRAEENIR SLMSAEKTKG FCQLVVSSNL RDGASHLIQS 790 800 810 820 830 840 AGLGGMKHNT VLMAWPEAWK EADNPFSWKN FVDTVRDTTA AHQALLVAKN IDLFPQNQER 850 860 870 880 890 900 FSDGNIDVWW IVHDGGMLML LPFLLRQHKV WRKCRMRIFT VAQVDDNSIQ MKKDLQMFLY 910 920 930 940 950 960 HLRISAEVEV VEMVENDISA FTYEKTLMME QRSQMLKQMQ LSKNEREREA QLIHDRNTAS 970 980 990 1000 1010 1020 HTTATARTQA PPTPDKVQMT WTKEKLIAEK HRNKDTGPSG FKDLFSLKPD QSNVRRMHTA 1030 1040 1050 1060 1070 1080 VKLNGVVLNK SQDAQLVLLN MPGPPKSRQG DENYMEFLEV LTEGLNRVLL VRGGGREVIT IYS
	Isoform 2 [UniParc]. Checksum: 1F3DDB7BC541B893	FASTA	1,054	116,549
	10 20 30 40 50 60 MPTNFTVVPV EARADGAGDE AAERTEEPES PESVDQTSPT PGDGNPRENS PFINNVEVER 70 80 90 100 110 120 ESYFEGKNMA LFEEEMDSNP MVSSLLNKLA NYTNLSQGVV EHEEDEDSRR REVKAPRMGT 130 140 150 160 170 180 FIGVYLPCLQ NILGVILFLR LTWIVGAAGV MESFLIVAMC CTCTMLTAIS MSAIATNGVV 190 200 210 220 230 240 PAGGSYYMIS RSLGPEFGGA VGLCFYLGTT FAGAMYILGT IEIFLTYISP SAAIFQAETA 250 260 270 280 290 300 DGEAAALLNN MRVYGSCALA LMAVVVFVGV KYVNKLALVF LACVVLSILA IYAGVIKTAF 310 320 330 340 350 360 APPDIPVCLL GNRTLANRNF DTCAKMQVVS NGTVTTALWR LFCNGSSLGA TCDEYFAQNN 370 380 390 400 410 420 VTEIQGIPGV ASGVFLDNLW STYSDKGAFV EKKGVSSVPV SEESRPGGLP YVLTDIMTYF 430 440 450 460 470 480 TMLVGIYFPS VTGIMAGSNR SGDLKDAQKS IPTGTILAIV TTSFIYLSCI VLFGACIEGV 490 500 510 520 530 540 VLRDKFGEAL QGNLVIGMLA WPSPWVIVIG SFFSTCGAGL QSLTGAPRLL QAIARDGIIP 550 560 570 580 590 600 FLQVFGHGKA NGEPTWALLL TALICETGIL IASLDSVAPI LSMFFLMCYM FVNLACAVQT 610 620 630 640 650 660 LLRTPNWRPR FKFYHWTLSF LGMSLCLALM FICSWYYALF AMLIAGCIYK YIEYRGAEKE 670 680 690 700 710 720 WGDGIRGLSL NAARYALLRV EHGPPHTKNW RPQVLVMLNL DSEQCVKHPR LLSFTSQLKA 730 740 750 760 770 780 GKGLTIVGSV LEGTYLDKHV EAQRAEENIR SLMSAEKTKG FCQLVVSSNL RDGASHLIQS 790 800 810 820 830 840 AGLGGMKHNT VLMAWPEAWK EADNPFSWKN FVDTVRDTTA AHQALLVAKN IDLFPQNQER 850 860 870 880 890 900 FSDGNIDVWW IVHDGGMLML LPFLLRQHKV WRKCRMRIFT VAQVDDNSIQ MKKDLQMFLY 910 920 930 940 950 960 HLRISAEVEV VEMVENDISA FTYEKTLMME QRSQMLKQMQ LSKNEREREA QLIHDRNTAS 970 980 990 1000 1010 1020 HTTATARTQA PPTPDKVQMT WTKEKLIAEK HRNKDTGPSG FKDLFSLKPL LHFMLFENRC 1030 1040 1050 WTKHTVIVPF PWSEFRVPVM KGLTGATETH LIYS

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).
[2]	"Prediction of the coding sequences of mouse homologues of FLJ genes: the complete nucleotide sequences of 110 mouse FLJ-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries." Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Kitamura H., Nakagawa T., Nagase T., Ohara O., Koga H. DNA Res. 11:127-135(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Embryonic tail.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1079 (ISOFORM 1). Strain: C57BL/6J and NOD. Tissue: Bone marrow and Dendritic cell.
[4]	"A dominant negative mutant of the KCC1 K-Cl cotransporter: both N- and C-terminal cytoplasmic domains are required for K-Cl cotransport activity." Casula S., Shmukler B.E., Wilhelm S., Stuart-Tilley A.K., Su W., Chernova M.N., Brugnara C., Alper S.L. J. Biol. Chem. 276:41870-41878(2001) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT.
[5]	"Deafness and renal tubular acidosis in mice lacking the K-Cl co-transporter Kcc4." Boettger T., Huebner C.A., Maier H., Rust M.B., Beck F.X., Jentsch T.J. Nature 416:874-878(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISEASE.
[6]	"The phagosomal proteome in interferon-gamma-activated macrophages." Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P. Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-37; SER-50; THR-926 AND THR-980, MASS SPECTROMETRY. Tissue: Macrophage.
[7]	"The mouse C2C12 myoblast cell surface N-linked glycoproteome: identification, glycosite occupancy, and membrane orientation." Gundry R.L., Raginski K., Tarasova Y., Tchernyshyov I., Bausch-Fluck D., Elliott S.T., Boheler K.R., Van Eyk J.E., Wollscheid B. Mol. Cell. Proteomics 8:2555-2569(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-331, MASS SPECTROMETRY. Tissue: Myoblast.
[8]	"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins." Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D. Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-331, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF087436 mRNA. Translation: AAD38328.1. AK131129 mRNA. Translation: BAD21379.1. Different initiation. AK149750 mRNA. Translation: BAE29061.1. AK169950 mRNA. Translation: BAE41477.1. AK171498 mRNA. Translation: BAE42491.1. Frameshift.
IPI	IPI00331175. IPI00856645.
RefSeq	NP_035520.1. NM_011390.2.
UniGene	Mm.275800.
3D structure databases
ProteinModelPortal	Q9WVL3.
SMR	Q9WVL3. Positions 425-595.
ModBase	Search...
PTM databases
PhosphoSite	Q9WVL3.
Proteomic databases
PaxDb	Q9WVL3.
PRIDE	Q9WVL3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000017900; ENSMUSP00000017900; ENSMUSG00000017756.
GeneID	20499.
KEGG	mmu:20499.
UCSC	uc007reb.1. mouse.
Organism-specific databases
CTD	10723.
MGI	MGI:1342283. Slc12a7.
Phylogenomic databases
eggNOG	COG0531.
GeneTree	ENSGT00560000076892.
HOGENOM	HOG000092644.
HOVERGEN	HBG052852.
InParanoid	Q9WVL3.
KO	K13627.
OMA	EDNPFSW.
OrthoDB	EOG4THVS8.
Gene expression databases
ArrayExpress	Q9WVL3.
Bgee	Q9WVL3.
CleanEx	MM_SLC12A7.
Genevestigator	Q9WVL3.
GermOnline	ENSMUSG00000017756. Mus musculus.
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
NextBio	298663.
SOURCE	Search...

Entry information

Entry name

S12A7_MOUSE

Accession

Primary (citable) accession number: Q9WVL3
Secondary accession number(s): Q3TB23 , Q3TDX1, Q3UE50, Q6KAS8

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 13, 2002
Last sequence update:	November 1, 1999
Last modified:	May 1, 2013
This is version 92 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program