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Q9H2X9

- S12A5_HUMAN

UniProt

Q9H2X9 - S12A5_HUMAN

Protein

Solute carrier family 12 member 5

Gene

SLC12A5

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 117 (01 Oct 2014)
      Sequence version 3 (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 WNK3.1 Publication

    GO - Molecular functioni

    1. potassium:chloride symporter activity Source: UniProtKB
    2. protein kinase binding Source: BHF-UCL

    GO - Biological processi

    1. cellular ion homeostasis Source: UniProtKB
    2. chloride transmembrane transport Source: GOC
    3. ion transport Source: Reactome
    4. learning Source: Ensembl
    5. multicellular organism growth Source: Ensembl
    6. potassium ion transport Source: UniProtKB-KW
    7. response to drug Source: Ensembl
    8. synaptic transmission Source: Ensembl
    9. thermosensory behavior Source: Ensembl
    10. transmembrane transport Source: Reactome
    11. transport Source: UniProtKB

    Keywords - Biological processi

    Ion transport, Potassium transport, Symport, Transport

    Keywords - Ligandi

    Potassium

    Enzyme and pathway databases

    ReactomeiREACT_19315. Cation-coupled Chloride cotransporters.

    Protein family/group databases

    TCDBi2.A.30.5.6. the cation-chloride cotransporter (ccc) family.

    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:
    hKCC2
    Neuronal K-Cl cotransporter
    Gene namesi
    Name:SLC12A5
    Synonyms:KCC2, KIAA1176
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 20

    Organism-specific databases

    HGNCiHGNC:13818. SLC12A5.

    Subcellular locationi

    GO - Cellular componenti

    1. dendritic shaft Source: Ensembl
    2. integral component of membrane Source: UniProtKB
    3. neuronal cell body Source: Ensembl
    4. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA37814.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 11391139Solute carrier family 12 member 5PRO_0000178034Add
    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

    MaxQBiQ9H2X9.
    PaxDbiQ9H2X9.
    PRIDEiQ9H2X9.

    PTM databases

    PhosphoSiteiQ9H2X9.

    Expressioni

    Tissue specificityi

    Brain specific. Detected in neuronal cells.

    Gene expression databases

    ArrayExpressiQ9H2X9.
    BgeeiQ9H2X9.
    CleanExiHS_SLC12A5.
    GenevestigatoriQ9H2X9.

    Interactioni

    Subunit structurei

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

    Protein-protein interaction databases

    STRINGi9606.ENSP00000387694.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9H2X9.
    SMRiQ9H2X9. 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 – 1139271CytoplasmicSequence 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.
    HOGENOMiHOG000092644.
    HOVERGENiHBG052852.
    InParanoidiQ9H2X9.
    KOiK14427.
    OMAiHLTWTKD.
    OrthoDBiEOG78M01J.
    PhylomeDBiQ9H2X9.
    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: Q9H2X9-1) [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 PPAGPARSPD PESRRHSVAD PRHLPGEDVK GDGNPKESSP     50
    FINSTDTEKG KEYDGKNMAL 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 WGLFCSSRFL 350
    NATCDEYFTR NNVTEIQGIP GAASGLIKEN LWSSYLTKGV IVERSGMTSV 400
    GLADGTPIDM 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 GSVLEGTFLE 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 NTRLRLNVPE ETAGDSEEKP EEEVQLIHDQ 1000
    SAPSCPSSSP SPGEEPEGEG ETDPEKVHLT WTKDKSVAEK NKGPSPVSSE 1050
    GIKDFFSMKP EWENLNQSNV RRMHTAVRLN EVIVKKSRDA KLVLLNMPGP 1100
    PRNRNGDENY MEFLEVLTEH LDRVMLVRGG GREVITIYS 1139
    Length:1,139
    Mass (Da):126,184
    Last modified:December 4, 2007 - v3
    Checksum:i100C097AF1FD4B3E
    GO
    Isoform 2 (identifier: Q9H2X9-2) [UniParc]FASTAAdd to Basket

    Also known as: KCC2b

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

    Show »
    Length:1,116
    Mass (Da):123,511
    Checksum:i68D46DECF8592FCF
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Isoform 2 (identifier: Q9H2X9-2)
    Sequence conflicti2 – 21L → P in AAG43493. (PubMed:12106695)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti407 – 4071P → A.
    Corresponds to variant rs16985442 [ dbSNP | Ensembl ].
    VAR_027414
    Natural varianti847 – 8471G → D in a colorectal cancer sample; somatic mutation. 1 Publication
    VAR_036557
    Natural varianti1100 – 11001P → L.1 Publication
    Corresponds to variant rs17297532 [ dbSNP | Ensembl ].
    VAR_024994

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 4040MSRRF…GEDVK → MLNNLTDCEDGDGGANP in isoform 2. 3 PublicationsVSP_029909Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF208159 mRNA. Translation: AAG43493.1.
    AL162458 Genomic DNA. Translation: CAH74054.2.
    BC132668 mRNA. Translation: AAI32669.1.
    BC132670 mRNA. Translation: AAI32671.1.
    AB033002 mRNA. Translation: BAA86490.1.
    DA102113 mRNA. No translation available.
    DA328785 mRNA. No translation available.
    CCDSiCCDS13391.1. [Q9H2X9-2]
    CCDS46610.1. [Q9H2X9-1]
    RefSeqiNP_001128243.1. NM_001134771.1. [Q9H2X9-1]
    NP_065759.1. NM_020708.4. [Q9H2X9-2]
    UniGeneiHs.21413.

    Genome annotation databases

    EnsembliENST00000243964; ENSP00000243964; ENSG00000124140. [Q9H2X9-2]
    ENST00000454036; ENSP00000387694; ENSG00000124140. [Q9H2X9-1]
    GeneIDi57468.
    KEGGihsa:57468.
    UCSCiuc002xrb.2. human. [Q9H2X9-2]
    uc010zxl.1. human. [Q9H2X9-1]

    Polymorphism databases

    DMDMi161784306.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF208159 mRNA. Translation: AAG43493.1 .
    AL162458 Genomic DNA. Translation: CAH74054.2 .
    BC132668 mRNA. Translation: AAI32669.1 .
    BC132670 mRNA. Translation: AAI32671.1 .
    AB033002 mRNA. Translation: BAA86490.1 .
    DA102113 mRNA. No translation available.
    DA328785 mRNA. No translation available.
    CCDSi CCDS13391.1. [Q9H2X9-2 ]
    CCDS46610.1. [Q9H2X9-1 ]
    RefSeqi NP_001128243.1. NM_001134771.1. [Q9H2X9-1 ]
    NP_065759.1. NM_020708.4. [Q9H2X9-2 ]
    UniGenei Hs.21413.

    3D structure databases

    ProteinModelPortali Q9H2X9.
    SMRi Q9H2X9. Positions 412-662.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9606.ENSP00000387694.

    Chemistry

    ChEMBLi CHEMBL1615384.
    DrugBanki DB00887. Bumetanide.
    DB00761. Potassium Chloride.
    GuidetoPHARMACOLOGYi 972.

    Protein family/group databases

    TCDBi 2.A.30.5.6. the cation-chloride cotransporter (ccc) family.

    PTM databases

    PhosphoSitei Q9H2X9.

    Polymorphism databases

    DMDMi 161784306.

    Proteomic databases

    MaxQBi Q9H2X9.
    PaxDbi Q9H2X9.
    PRIDEi Q9H2X9.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000243964 ; ENSP00000243964 ; ENSG00000124140 . [Q9H2X9-2 ]
    ENST00000454036 ; ENSP00000387694 ; ENSG00000124140 . [Q9H2X9-1 ]
    GeneIDi 57468.
    KEGGi hsa:57468.
    UCSCi uc002xrb.2. human. [Q9H2X9-2 ]
    uc010zxl.1. human. [Q9H2X9-1 ]

    Organism-specific databases

    CTDi 57468.
    GeneCardsi GC20P044651.
    HGNCi HGNC:13818. SLC12A5.
    MIMi 606726. gene.
    neXtProti NX_Q9H2X9.
    PharmGKBi PA37814.
    HUGEi Search...
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0531.
    HOGENOMi HOG000092644.
    HOVERGENi HBG052852.
    InParanoidi Q9H2X9.
    KOi K14427.
    OMAi HLTWTKD.
    OrthoDBi EOG78M01J.
    PhylomeDBi Q9H2X9.
    TreeFami TF313657.

    Enzyme and pathway databases

    Reactomei REACT_19315. Cation-coupled Chloride cotransporters.

    Miscellaneous databases

    GeneWikii Chloride_potassium_symporter_5.
    GenomeRNAii 57468.
    NextBioi 63686.
    PROi Q9H2X9.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9H2X9.
    Bgeei Q9H2X9.
    CleanExi HS_SLC12A5.
    Genevestigatori Q9H2X9.

    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. "Molecular, functional, and genomic characterization of human KCC2, the neuronal K-Cl cotransporter."
      Song L., Mercado A., Vazquez N., Xie Q., Desai R., George A.L. Jr., Gamba G., Mount D.B.
      Brain Res. Mol. Brain Res. 103:91-105(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
      Tissue: Brain.
    2. "The DNA sequence and comparative analysis of human chromosome 20."
      Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E.
      , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
      Nature 414:865-871(2001) [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] (ISOFORM 2).
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-175 (ISOFORM 1).
    5. "Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain."
      Hirosawa M., Nagase T., Ishikawa K., Kikuno R., Nomura N., Ohara O.
      DNA Res. 6:329-336(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 9-1109 (ISOFORM 2), VARIANT LEU-1100.
      Tissue: Brain.
    6. Cited for: ENZYME REGULATION.
    7. Cited for: VARIANT [LARGE SCALE ANALYSIS] ASP-847.

    Entry informationi

    Entry nameiS12A5_HUMAN
    AccessioniPrimary (citable) accession number: Q9H2X9
    Secondary accession number(s): A2RTX2
    , Q5VZ41, Q9H4Z0, Q9ULP4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 13, 2002
    Last sequence update: December 4, 2007
    Last modified: October 1, 2014
    This is version 117 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny 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.

    Miscellaneousi

    Miscellaneous

    Inhibited by furosemide and bumetanide.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 20
      Human chromosome 20: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3