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Q9WVL3 (S12A7_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

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 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

Cell membrane; Multi-pass membrane protein Ref.10.

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.

Post-translational modification

Glycosylation at Asn-331 and Asn-344 is required for proper trafficking to the cell surface, and augments protein stability.

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. Translation N-terminally shortened.

The sequence BAE42491.1 differs from that shown. Reason: Frameshift at position 32.

Ontologies

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10831083Solute carrier family 12 member 7
PRO_0000178040

Regions

Topological domain1 – 118118Cytoplasmic Potential
Transmembrane119 – 13921Helical; Potential
Transmembrane141 – 16121Helical; Potential
Topological domain162 – 20039Cytoplasmic Potential
Transmembrane201 – 22121Helical; 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 residue301Phosphoserine Ref.7
Modified residue331Phosphoserine Ref.7
Modified residue371Phosphothreonine Ref.7
Modified residue501Phosphoserine Ref.6 Ref.7
Modified residue621Phosphoserine By similarity
Glycosylation3121N-linked (GlcNAc...) (high mannose) Ref.10
Glycosylation3311N-linked (GlcNAc...) (complex) Ref.8 Ref.9 Ref.10
Glycosylation3441N-linked (GlcNAc...) (complex) Ref.10
Glycosylation3601N-linked (GlcNAc...) (high mannose) Ref.10

Natural variations

Alternative sequence1010 – 108071DQSNV…REVIT → LLHFMLFENRCWTKHTVIVP FPWSEFRVPVMKGLTGATET HL in isoform 2.
VSP_027770

Experimental info

Sequence conflict401T → M in BAE41477. Ref.3
Sequence conflict3551Y → F in BAE41477. Ref.3
Sequence conflict9511Q → P in BAE29061. Ref.3

Sequences

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

Last modified November 1, 1999. Version 1.
Checksum: E339D43F7D3B6BD7

FASTA1,083119,481
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 1F3DDB7BC541B893
Show »

FASTA1,054116,549

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).
[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. expand/collapse author list , 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]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-50, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[7]"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 SER-30; SER-33; THR-37 AND SER-50, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"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.
Tissue: Myoblast.
[9]"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.
[10]"Glycosylation regulates the function and membrane localization of KCC4."
Weng T.Y., Chiu W.T., Liu H.S., Cheng H.C., Shen M.R., Mount D.B., Chou C.Y.
Biochim. Biophys. Acta 1833:1133-1146(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-312; ASN-331; ASN-344 AND ASN-360.
+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.
CCDSCCDS26635.1. [Q9WVL3-1]
RefSeqNP_035520.1. NM_011390.2. [Q9WVL3-1]
UniGeneMm.275800.

3D structure databases

ProteinModelPortalQ9WVL3.
SMRQ9WVL3. Positions 425-595.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteQ9WVL3.

Proteomic databases

MaxQBQ9WVL3.
PaxDbQ9WVL3.
PRIDEQ9WVL3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000017900; ENSMUSP00000017900; ENSMUSG00000017756. [Q9WVL3-1]
GeneID20499.
KEGGmmu:20499.
UCSCuc007rec.1. mouse. [Q9WVL3-1]

Organism-specific databases

CTD10723.
MGIMGI:1342283. Slc12a7.

Phylogenomic databases

eggNOGCOG0531.
GeneTreeENSGT00560000076892.
HOGENOMHOG000092644.
HOVERGENHBG052852.
InParanoidQ9WVL3.
KOK13627.
OMALIVAMCC.
OrthoDBEOG78M01J.
PhylomeDBQ9WVL3.
TreeFamTF313657.

Gene expression databases

ArrayExpressQ9WVL3.
BgeeQ9WVL3.
CleanExMM_SLC12A7.
GenevestigatorQ9WVL3.

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

NextBio298663.
PROQ9WVL3.
SOURCESearch...

Entry information

Entry nameS12A7_MOUSE
AccessionPrimary (citable) accession number: Q9WVL3
Secondary accession number(s): Q3TB23 expand/collapse secondary AC list , Q3TDX1, Q3UE50, Q6KAS8
Entry history
Integrated into UniProtKB/Swiss-Prot: December 13, 2002
Last sequence update: November 1, 1999
Last modified: July 9, 2014
This is version 104 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot