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Q9WVL3

- S12A7_MOUSE

UniProt

Q9WVL3 - S12A7_MOUSE

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Protein
Solute carrier family 12 member 7
Gene
Slc12a7, Kcc4
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.1 Publication

Enzyme regulationi

Inhibited by WNK3 By similarity.

GO - Molecular functioni

  1. potassium:chloride symporter activity Source: InterPro

GO - Biological processi

  1. cell volume homeostasis Source: Ensembl
  2. potassium ion transport Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Ion transport, Potassium transport, Symport, Transport

Keywords - Ligandi

Potassium

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 13

Organism-specific databases

MGIiMGI:1342283. Slc12a7.

Subcellular locationi

Cell membrane; Multi-pass membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 118118Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei119 – 13921Helical; Reviewed prediction
Add
BLAST
Transmembranei141 – 16121Helical; Reviewed prediction
Add
BLAST
Topological domaini162 – 20039Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei201 – 22121Helical; Reviewed prediction
Add
BLAST
Transmembranei253 – 27321Helical; Reviewed prediction
Add
BLAST
Topological domaini274 – 2752Cytoplasmic Reviewed prediction
Transmembranei276 – 29621Helical; Reviewed prediction
Add
BLAST
Transmembranei416 – 43621Helical; Reviewed prediction
Add
BLAST
Topological domaini437 – 45620Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei457 – 47721Helical; Reviewed prediction
Add
BLAST
Transmembranei494 – 51421Helical; Reviewed prediction
Add
BLAST
Topological domaini515 – 55339Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei554 – 57421Helical; Reviewed prediction
Add
BLAST
Transmembranei578 – 59821Helical; Reviewed prediction
Add
BLAST
Topological domaini599 – 62426Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei625 – 64521Helical; Reviewed prediction
Add
BLAST
Transmembranei845 – 86521Helical; Reviewed prediction
Add
BLAST
Topological domaini866 – 1083218Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. integral component of membrane Source: UniProtKB-KW
  2. plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

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.1 Publication

Keywords - Diseasei

Deafness

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10831083Solute carrier family 12 member 7
PRO_0000178040Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei30 – 301Phosphoserine1 Publication
Modified residuei33 – 331Phosphoserine1 Publication
Modified residuei37 – 371Phosphothreonine1 Publication
Modified residuei50 – 501Phosphoserine2 Publications
Modified residuei62 – 621Phosphoserine By similarity
Glycosylationi312 – 3121N-linked (GlcNAc...) (high mannose)1 Publication
Glycosylationi331 – 3311N-linked (GlcNAc...) (complex)3 Publications
Glycosylationi344 – 3441N-linked (GlcNAc...) (complex)1 Publication
Glycosylationi360 – 3601N-linked (GlcNAc...) (high mannose)1 Publication

Post-translational modificationi

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

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ9WVL3.
PaxDbiQ9WVL3.
PRIDEiQ9WVL3.

PTM databases

PhosphoSiteiQ9WVL3.

Expressioni

Tissue specificityi

Detected in proximal tubules in the kidney, in particular in basolateral membranes of intercalated cells in the cortical collecting duct.

Developmental stagei

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.

Gene expression databases

ArrayExpressiQ9WVL3.
BgeeiQ9WVL3.
CleanExiMM_SLC12A7.
GenevestigatoriQ9WVL3.

Interactioni

Subunit structurei

Homomultimer and heteromultimer with other K-Cl cotransporters Inferred.1 Publication

Structurei

3D structure databases

ProteinModelPortaliQ9WVL3.
SMRiQ9WVL3. Positions 425-595.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0531.
GeneTreeiENSGT00560000076892.
HOGENOMiHOG000092644.
HOVERGENiHBG052852.
InParanoidiQ9WVL3.
KOiK13627.
OMAiLIVAMCC.
OrthoDBiEOG78M01J.
PhylomeDBiQ9WVL3.
TreeFamiTF313657.

Family and domain databases

InterProiIPR004841. AA-permease/SLC12A_dom.
IPR000076. KCL_cotranspt.
IPR004842. Na/K/Cl_cotransptS.
[Graphical view]
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. Align

Isoform 1 (identifier: Q9WVL3-1) [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

MPTNFTVVPV EARADGAGDE AAERTEEPES PESVDQTSPT PGDGNPRENS     50
PFINNVEVER ESYFEGKNMA LFEEEMDSNP MVSSLLNKLA NYTNLSQGVV 100
EHEEDEDSRR REVKAPRMGT FIGVYLPCLQ NILGVILFLR LTWIVGAAGV 150
MESFLIVAMC CTCTMLTAIS MSAIATNGVV PAGGSYYMIS RSLGPEFGGA 200
VGLCFYLGTT FAGAMYILGT IEIFLTYISP SAAIFQAETA DGEAAALLNN 250
MRVYGSCALA LMAVVVFVGV KYVNKLALVF LACVVLSILA IYAGVIKTAF 300
APPDIPVCLL GNRTLANRNF DTCAKMQVVS NGTVTTALWR LFCNGSSLGA 350
TCDEYFAQNN VTEIQGIPGV ASGVFLDNLW STYSDKGAFV EKKGVSSVPV 400
SEESRPGGLP YVLTDIMTYF TMLVGIYFPS VTGIMAGSNR SGDLKDAQKS 450
IPTGTILAIV TTSFIYLSCI VLFGACIEGV VLRDKFGEAL QGNLVIGMLA 500
WPSPWVIVIG SFFSTCGAGL QSLTGAPRLL QAIARDGIIP FLQVFGHGKA 550
NGEPTWALLL TALICETGIL IASLDSVAPI LSMFFLMCYM FVNLACAVQT 600
LLRTPNWRPR FKFYHWTLSF LGMSLCLALM FICSWYYALF AMLIAGCIYK 650
YIEYRGAEKE WGDGIRGLSL NAARYALLRV EHGPPHTKNW RPQVLVMLNL 700
DSEQCVKHPR LLSFTSQLKA GKGLTIVGSV LEGTYLDKHV EAQRAEENIR 750
SLMSAEKTKG FCQLVVSSNL RDGASHLIQS AGLGGMKHNT VLMAWPEAWK 800
EADNPFSWKN FVDTVRDTTA AHQALLVAKN IDLFPQNQER FSDGNIDVWW 850
IVHDGGMLML LPFLLRQHKV WRKCRMRIFT VAQVDDNSIQ MKKDLQMFLY 900
HLRISAEVEV VEMVENDISA FTYEKTLMME QRSQMLKQMQ LSKNEREREA 950
QLIHDRNTAS HTTATARTQA PPTPDKVQMT WTKEKLIAEK HRNKDTGPSG 1000
FKDLFSLKPD QSNVRRMHTA VKLNGVVLNK SQDAQLVLLN MPGPPKSRQG 1050
DENYMEFLEV LTEGLNRVLL VRGGGREVIT IYS 1083
Length:1,083
Mass (Da):119,481
Last modified:November 1, 1999 - v1
Checksum:iE339D43F7D3B6BD7
GO
Isoform 2 (identifier: Q9WVL3-2) [UniParc]FASTAAdd to Basket

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

Note: No experimental confirmation available.

Show »
Length:1,054
Mass (Da):116,549
Checksum:i1F3DDB7BC541B893
GO

Sequence cautioni

The sequence BAE42491.1 differs from that shown. Reason: Frameshift at position 32.
The sequence BAD21379.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1010 – 108071DQSNV…REVIT → LLHFMLFENRCWTKHTVIVP FPWSEFRVPVMKGLTGATET HL in isoform 2.
VSP_027770Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti40 – 401T → M in BAE41477. 1 Publication
Sequence conflicti355 – 3551Y → F in BAE41477. 1 Publication
Sequence conflicti951 – 9511Q → P in BAE29061. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS26635.1. [Q9WVL3-1]
RefSeqiNP_035520.1. NM_011390.2. [Q9WVL3-1]
UniGeneiMm.275800.

Genome annotation databases

EnsembliENSMUST00000017900; ENSMUSP00000017900; ENSMUSG00000017756. [Q9WVL3-1]
GeneIDi20499.
KEGGimmu:20499.
UCSCiuc007rec.1. mouse. [Q9WVL3-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSi CCDS26635.1. [Q9WVL3-1 ]
RefSeqi NP_035520.1. NM_011390.2. [Q9WVL3-1 ]
UniGenei Mm.275800.

3D structure databases

ProteinModelPortali Q9WVL3.
SMRi Q9WVL3. Positions 425-595.
ModBasei Search...
MobiDBi Search...

PTM databases

PhosphoSitei Q9WVL3.

Proteomic databases

MaxQBi Q9WVL3.
PaxDbi Q9WVL3.
PRIDEi Q9WVL3.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000017900 ; ENSMUSP00000017900 ; ENSMUSG00000017756 . [Q9WVL3-1 ]
GeneIDi 20499.
KEGGi mmu:20499.
UCSCi uc007rec.1. mouse. [Q9WVL3-1 ]

Organism-specific databases

CTDi 10723.
MGIi MGI:1342283. Slc12a7.

Phylogenomic databases

eggNOGi COG0531.
GeneTreei ENSGT00560000076892.
HOGENOMi HOG000092644.
HOVERGENi HBG052852.
InParanoidi Q9WVL3.
KOi K13627.
OMAi LIVAMCC.
OrthoDBi EOG78M01J.
PhylomeDBi Q9WVL3.
TreeFami TF313657.

Miscellaneous databases

NextBioi 298663.
PROi Q9WVL3.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q9WVL3.
Bgeei Q9WVL3.
CleanExi MM_SLC12A7.
Genevestigatori Q9WVL3.

Family and domain databases

InterProi IPR004841. AA-permease/SLC12A_dom.
IPR000076. KCL_cotranspt.
IPR004842. Na/K/Cl_cotransptS.
[Graphical view ]
Pfami PF00324. AA_permease. 2 hits.
[Graphical view ]
PRINTSi PR01081. KCLTRNSPORT.
TIGRFAMsi TIGR00930. 2a30. 1 hit.
ProtoNeti Search...

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).
  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. 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.

Entry informationi

Entry nameiS12A7_MOUSE
AccessioniPrimary (citable) accession number: Q9WVL3
Secondary accession number(s): Q3TB23
, Q3TDX1, Q3UE50, Q6KAS8
Entry historyi
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 statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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