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Q91V14

- S12A5_MOUSE

UniProt

Q91V14 - S12A5_MOUSE

Protein

Solute carrier family 12 member 5

Gene

Slc12a5

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 114 (01 Oct 2014)
      Sequence version 2 (04 Dec 2007)
      Previous versions | rss
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    Functioni

    Mediates electroneutral potassium-chloride cotransport in mature neurons. Transport occurs under isotonic conditions, but is activated 20-fold by cell swelling. Important for Cl- homeostasis in neurons.

    Enzyme regulationi

    Inhibited by WNK3.By similarity

    GO - Molecular functioni

    1. potassium:chloride symporter activity Source: MGI
    2. protein binding Source: MGI

    GO - Biological processi

    1. chloride transmembrane transport Source: GOC
    2. chloride transport Source: MGI
    3. learning Source: MGI
    4. multicellular organism growth Source: MGI
    5. potassium ion transport Source: UniProtKB-KW
    6. response to drug Source: MGI
    7. synaptic transmission Source: MGI
    8. thermosensory behavior Source: MGI

    Keywords - Biological processi

    Ion transport, Potassium transport, Symport, Transport

    Keywords - Ligandi

    Potassium

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Solute carrier family 12 member 5
    Alternative name(s):
    Electroneutral potassium-chloride cotransporter 2
    K-Cl cotransporter 2
    Short name:
    mKCC2
    Neuronal K-Cl cotransporter
    Gene namesi
    Name:Slc12a5
    Synonyms:Kcc2, Kiaa1176
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 2

    Organism-specific databases

    MGIiMGI:1862037. Slc12a5.

    Subcellular locationi

    Cell projectiondendrite 1 Publication. Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication
    Note: Detected on dendrites, but not on axons of spinal cord neurons and at GPHN-positive inhibitory synapses.

    GO - Cellular componenti

    1. dendritic shaft Source: MGI
    2. integral component of membrane Source: UniProtKB-KW
    3. neuronal cell body Source: MGI
    4. plasma membrane Source: MGI

    Keywords - Cellular componenti

    Cell membrane, Cell projection, Membrane

    Pathology & Biotechi

    Disruption phenotypei

    Death at birth due to severe motor deficits including respiratory failure. Mice lacking isoform 2 die within 2 weeks after birth.1 Publication

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi680 – 6812LL → AA: Inhibits endocytosis. Abolishes interaction with AP2A1. 1 Publication
    Mutagenesisi684 – 6852EE → AA: Decreases endocytosis. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 11381138Solute carrier family 12 member 5PRO_0000178035Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi442 – 4421N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi833 – 8331N-linked (GlcNAc...)Sequence Analysis

    Keywords - PTMi

    Glycoprotein

    Proteomic databases

    MaxQBiQ91V14.
    PaxDbiQ91V14.
    PRIDEiQ91V14.

    PTM databases

    PhosphoSiteiQ91V14.

    Expressioni

    Tissue specificityi

    Isoform 2 expressed in brainstem and spinal cord, isoform 1 expressed in brainstem, spinal cord and olfactory bulb of E17 embryos. Isoforms 1 and 2 expressed in all parts of the brain and spinal cord in postnatal day 14 mice.1 Publication

    Developmental stagei

    Isoform 1 predominant isoform in E17 brain. Isoform 2 predominant isoform during postnatal development. Detected in the ventral horns of the spinal cord at E12.5, and throughout the spinal cord at birth.

    Gene expression databases

    ArrayExpressiQ91V14.
    CleanExiMM_SLC12A5.
    GenevestigatoriQ91V14.

    Interactioni

    Subunit structurei

    Homomultimer and heteromultimer with other K-Cl cotransporters By similarity. Interacts with AP2A1.By similarity1 Publication

    Protein-protein interaction databases

    IntActiQ91V14. 4 interactions.
    MINTiMINT-4133713.

    Structurei

    3D structure databases

    ProteinModelPortaliQ91V14.
    SMRiQ91V14. Positions 412-662.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 133133CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini177 – 19418CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini238 – 25417CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini299 – 418120CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini480 – 49617CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini591 – 63040CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini869 – 1138270CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei134 – 15421HelicalSequence AnalysisAdd
    BLAST
    Transmembranei156 – 17621HelicalSequence AnalysisAdd
    BLAST
    Transmembranei195 – 21521HelicalSequence AnalysisAdd
    BLAST
    Transmembranei217 – 23721HelicalSequence AnalysisAdd
    BLAST
    Transmembranei255 – 27521HelicalSequence AnalysisAdd
    BLAST
    Transmembranei278 – 29821HelicalSequence AnalysisAdd
    BLAST
    Transmembranei419 – 43921HelicalSequence AnalysisAdd
    BLAST
    Transmembranei459 – 47921HelicalSequence AnalysisAdd
    BLAST
    Transmembranei497 – 51721HelicalSequence AnalysisAdd
    BLAST
    Transmembranei570 – 59021HelicalSequence AnalysisAdd
    BLAST
    Transmembranei631 – 65121HelicalSequence AnalysisAdd
    BLAST
    Transmembranei848 – 86821HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the SLC12A transporter family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0531.
    GeneTreeiENSGT00560000076892.
    HOGENOMiHOG000092644.
    HOVERGENiHBG052852.
    InParanoidiQ91V14.
    KOiK14427.
    OMAiHLTWTKD.
    OrthoDBiEOG78M01J.
    PhylomeDBiQ91V14.
    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: Q91V14-1) [UniParc]FASTAAdd to Basket

    Also known as: KCC2a

    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

    MSRRFTVTSL PPAASAASAD PESRRHSVAD PRRLPREDVK GDGNPKESSP     50
    FINSTDTEKG REYDGRNMAL FEEEMDTSPM VSSLLSGLAN YTNLPQGSRE 100
    HEEAENNEGG KKKPVQAPRM GTFMGVYLPC LQNIFGVILF LRLTWVVGIA 150
    GIMESFCMVF ICCSCTMLTA ISMSAIATNG VVPAGGSYYM ISRSLGPEFG 200
    GAVGLCFYLG TTFAGAMYIL GTIEILLAYL FPAMAIFKAE DASGEAAAML 250
    NNMRVYGTCV LTCMATVVFV GVKYVNKFAL VFLGCVILSI LAIYAGVIKS 300
    AFDPPNFPIC LLGNRTLSRH GFDVCAKLAW EGNETVTTRL WGLFCSSRLL 350
    NATCDEYFTR NNVTEIQGIP GAASGLIKEN LWSSYLTKGV IVERRGMPSV 400
    GLADGTPVDM DHPYVFSDMT SYFTLLVGIY FPSVTGIMAG SNRSGDLRDA 450
    QKSIPTGTIL AIATTSAVYI SSVVLFGACI EGVVLRDKFG EAVNGNLVVG 500
    TLAWPSPWVI VIGSFFSTCG AGLQSLTGAP RLLQAISRDG IVPFLQVFGH 550
    GKANGEPTWA LLLTACICEI GILIASLDEV APILSMFFLM CYMFVNLACA 600
    VQTLLRTPNW RPRFRYYHWT LSFLGMSLCL ALMFICSWYY ALVAMLIAGL 650
    IYKYIEYRGA EKEWGDGIRG LSLSAARYAL LRLEEGPPHT KNWRPQLLVL 700
    VRVDQDQNVV HPQLLSLTSQ LKAGKGLTIV GSVLEGTFLD NHPQAQRAEE 750
    SIRRLMEAEK VKGFCQVVIS SNLRDGVSHL IQSGGLGGLQ HNTVLVGWPR 800
    NWRQKEDHQT WRNFIELVRE TTAGHLALLV TKNVSMFPGN PERFSEGSID 850
    VWWIVHDGGM LMLLPFLLRH HKVWRKCKMR IFTVAQMDDN SIQMKKDLTT 900
    FLYHLRITAE VEVVEMHESD ISAYTYEKTL VMEQRSQILK QMHLTKNERE 950
    REIQSITDES RGSIRRKNPA NPRLRLNVPE ETACDNEEKP EEEVQLIHDQ 1000
    SAPSCPSSSP SPGEEPEGER ETDPEVHLTW TKDKSVAEKN KGPSPVSSEG 1050
    IKDFFSMKPE WENLNQSNVR RMHTAVRLNE VIVNKSRDAK LVLLNMPGPP 1100
    RNRNGDENYM EFLEVLTEQL DRVMLVRGGG REVITIYS 1138
    Length:1,138
    Mass (Da):126,271
    Last modified:December 4, 2007 - v2
    Checksum:i56059F065B89C407
    GO
    Isoform 2 (identifier: Q91V14-2) [UniParc]FASTAAdd to Basket

    Also known as: KCC2b

    The sequence of this isoform differs from the canonical sequence as follows:
         1-40: MSRRFTVTSLPPAASAASADPESRRHSVADPRRLPREDVK → MLNNLTDCEDGDGGANP

    Show »
    Length:1,115
    Mass (Da):123,587
    Checksum:iDD506AC24D8492B4
    GO

    Sequence cautioni

    The sequence BAC65742.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti64 – 641Missing in AAH54808. (PubMed:15489334)Curated
    Sequence conflicti859 – 8591G → D in BAE27805. (PubMed:16141072)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 4040MSRRF…REDVK → MLNNLTDCEDGDGGANP in isoform 2. 4 PublicationsVSP_029910Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF332063 mRNA. Translation: AAK56092.1.
    AF332064 mRNA. Translation: AAK56093.1.
    AK122460 mRNA. Translation: BAC65742.1. Different initiation.
    AK147262 mRNA. Translation: BAE27805.1.
    AL591495 Genomic DNA. Translation: CAM26466.1.
    BC054808 mRNA. Translation: AAH54808.1.
    AJ011033 Genomic DNA. Translation: CAA09464.1.
    CCDSiCCDS38332.1. [Q91V14-2]
    RefSeqiNP_065066.2. NM_020333.2. [Q91V14-2]
    UniGeneiMm.252987.

    Genome annotation databases

    EnsembliENSMUST00000099092; ENSMUSP00000096690; ENSMUSG00000017740. [Q91V14-2]
    GeneIDi57138.
    KEGGimmu:57138.
    UCSCiuc008nwu.2. mouse. [Q91V14-2]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF332063 mRNA. Translation: AAK56092.1 .
    AF332064 mRNA. Translation: AAK56093.1 .
    AK122460 mRNA. Translation: BAC65742.1 . Different initiation.
    AK147262 mRNA. Translation: BAE27805.1 .
    AL591495 Genomic DNA. Translation: CAM26466.1 .
    BC054808 mRNA. Translation: AAH54808.1 .
    AJ011033 Genomic DNA. Translation: CAA09464.1 .
    CCDSi CCDS38332.1. [Q91V14-2 ]
    RefSeqi NP_065066.2. NM_020333.2. [Q91V14-2 ]
    UniGenei Mm.252987.

    3D structure databases

    ProteinModelPortali Q91V14.
    SMRi Q91V14. Positions 412-662.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi Q91V14. 4 interactions.
    MINTi MINT-4133713.

    PTM databases

    PhosphoSitei Q91V14.

    Proteomic databases

    MaxQBi Q91V14.
    PaxDbi Q91V14.
    PRIDEi Q91V14.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000099092 ; ENSMUSP00000096690 ; ENSMUSG00000017740 . [Q91V14-2 ]
    GeneIDi 57138.
    KEGGi mmu:57138.
    UCSCi uc008nwu.2. mouse. [Q91V14-2 ]

    Organism-specific databases

    CTDi 57468.
    MGIi MGI:1862037. Slc12a5.
    Rougei Search...

    Phylogenomic databases

    eggNOGi COG0531.
    GeneTreei ENSGT00560000076892.
    HOGENOMi HOG000092644.
    HOVERGENi HBG052852.
    InParanoidi Q91V14.
    KOi K14427.
    OMAi HLTWTKD.
    OrthoDBi EOG78M01J.
    PhylomeDBi Q91V14.
    TreeFami TF313657.

    Miscellaneous databases

    NextBioi 313501.
    PROi Q91V14.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q91V14.
    CleanExi MM_SLC12A5.
    Genevestigatori Q91V14.

    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

    1. "High-throughput sequence identification of gene coding variants within alcohol-related QTLs."
      Ehringer M.A., Thompson J., Conroy O., Xu Y., Yang F., Canniff J., Beeson M., Gordon L., Bennett B., Johnson T.E., Sikela J.M.
      Mamm. Genome 12:657-663(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
      Strain: ILS and ISS.
    2. "Prediction of the coding sequences of mouse homologues of KIAA gene: II. The complete nucleotide sequences of 400 mouse KIAA-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., Aizawa H., Yuasa S., Nakajima D., Nagase T., Ohara O., Koga H.
      DNA Res. 10:35-48(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Tissue: Brain.
    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).
      Strain: C57BL/6.
      Tissue: Brain.
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    5. "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] (ISOFORM 2).
      Strain: C57BL/6.
      Tissue: Brain.
    6. "An efficient DNA sequencing strategy based on bacteriophage Mu in vitro DNA transposition reaction."
      Haapa S., Suomalainen S., Eerikaeinen S., Airaksinen M., Paulin L., Savilahti H.
      Genome Res. 9:308-315(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-227 (ISOFORM 2).
    7. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-72 (ISOFORM 1), TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
    8. Lubec G., Kang S.U.
      Submitted (APR-2007) to UniProtKB
      Cited for: PROTEIN SEQUENCE OF 532-538; 726-747; 813-819; 833-843; 952-961; 1042-1052; 1078-1085 AND 1091-1101, IDENTIFICATION BY MASS SPECTROMETRY.
      Strain: C57BL/6.
      Tissue: Brain.
    9. "Disruption of KCC2 reveals an essential role of K-Cl cotransport already in early synaptic inhibition."
      Huebner C.A., Stein V., Hermans-Borgmeyer I., Meyer T., Ballanyi K., Jentsch T.J.
      Neuron 30:515-524(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    10. "Identification of a novel di-leucine motif mediating K(+)/Cl(-) cotransporter KCC2 constitutive endocytosis."
      Zhao B., Wong A.Y.C., Murshid A., Bowie D., Presley J.F., Bedford F.K.
      Cell. Signal. 20:1769-1779(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH AP2A1, MUTAGENESIS OF 680-LEU-LEU-681 AND 684-GLU-GLU-685.

    Entry informationi

    Entry nameiS12A5_MOUSE
    AccessioniPrimary (citable) accession number: Q91V14
    Secondary accession number(s): A2A5L0
    , Q3UHQ2, Q7TQC9, Q80TI5, Q9Z0M7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 13, 2002
    Last sequence update: December 4, 2007
    Last modified: October 1, 2014
    This is version 114 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, 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