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P55011

- S12A2_HUMAN

UniProt

P55011 - S12A2_HUMAN

Protein

Solute carrier family 12 member 2

Gene

SLC12A2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 132 (01 Oct 2014)
      Sequence version 1 (01 Oct 1996)
      Previous versions | rss
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    Functioni

    Electrically silent transporter system. Mediates sodium and chloride reabsorption. Plays a vital role in the regulation of ionic balance and cell volume.

    Enzyme regulationi

    Activated by WNK3.1 Publication

    GO - Molecular functioni

    1. ammonium transmembrane transporter activity Source: UniProtKB
    2. protein binding Source: IntAct
    3. sodium:potassium:chloride symporter activity Source: ProtInc

    GO - Biological processi

    1. ammonium transmembrane transport Source: GOC
    2. ammonium transport Source: UniProtKB
    3. branching involved in mammary gland duct morphogenesis Source: Ensembl
    4. chloride transmembrane transport Source: GOC
    5. detection of mechanical stimulus involved in sensory perception of sound Source: Ensembl
    6. gamma-aminobutyric acid signaling pathway Source: Ensembl
    7. hyperosmotic response Source: Ensembl
    8. ion transport Source: Reactome
    9. mammary duct terminal end bud growth Source: Ensembl
    10. multicellular organism growth Source: Ensembl
    11. positive regulation of cell volume Source: Ensembl
    12. potassium ion transport Source: UniProtKB-KW
    13. sodium ion transport Source: UniProtKB-KW
    14. transepithelial ammonium transport Source: UniProtKB
    15. transepithelial chloride transport Source: UniProtKB
    16. transmembrane transport Source: Reactome
    17. transport Source: ProtInc

    Keywords - Biological processi

    Ion transport, Potassium transport, Sodium transport, Symport, Transport

    Keywords - Ligandi

    Potassium, Sodium

    Enzyme and pathway databases

    ReactomeiREACT_19315. Cation-coupled Chloride cotransporters.
    SignaLinkiP55011.

    Protein family/group databases

    TCDBi2.A.30.3.1. the cation-chloride cotransporter (ccc) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Solute carrier family 12 member 2
    Alternative name(s):
    Basolateral Na-K-Cl symporter
    Bumetanide-sensitive sodium-(potassium)-chloride cotransporter 1
    Gene namesi
    Name:SLC12A2
    Synonyms:NKCC1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:10911. SLC12A2.

    Subcellular locationi

    GO - Cellular componenti

    1. apical plasma membrane Source: Ensembl
    2. basolateral plasma membrane Source: Ensembl
    3. extracellular vesicular exosome Source: UniProt
    4. integral component of plasma membrane Source: ProtInc
    5. membrane Source: ProtInc
    6. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA35806.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 12121212Solute carrier family 12 member 2PRO_0000178023Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionine1 Publication
    Modified residuei77 – 771Phosphoserine1 Publication
    Modified residuei79 – 791Phosphoserine1 Publication
    Modified residuei266 – 2661PhosphothreonineBy similarity
    Modified residuei940 – 9401PhosphoserineBy similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    MaxQBiP55011.
    PaxDbiP55011.
    PRIDEiP55011.

    PTM databases

    PhosphoSiteiP55011.

    Expressioni

    Tissue specificityi

    Expressed in many tissues.

    Gene expression databases

    ArrayExpressiP55011.
    BgeeiP55011.
    CleanExiHS_SLC12A2.
    GenevestigatoriP55011.

    Organism-specific databases

    HPAiHPA020130.

    Interactioni

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    OXSR1O957472EBI-2801449,EBI-620853

    Protein-protein interaction databases

    BioGridi112447. 9 interactions.
    DIPiDIP-43979N.
    IntActiP55011. 4 interactions.
    MINTiMINT-5004359.
    STRINGi9606.ENSP00000262461.

    Structurei

    3D structure databases

    ProteinModelPortaliP55011.
    SMRiP55011. Positions 347-692.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 285285CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini307 – 31812ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini342 – 36625CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini388 – 41023ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini432 – 4354CytoplasmicSequence Analysis
    Topological domaini457 – 48630ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini508 – 52013CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini542 – 59150ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini613 – 65442CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini676 – 6805ExtracellularSequence Analysis
    Topological domaini700 – 72425CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini746 – 899154ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini921 – 1212292CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei286 – 30621HelicalSequence AnalysisAdd
    BLAST
    Transmembranei319 – 34123HelicalSequence AnalysisAdd
    BLAST
    Transmembranei367 – 38721HelicalSequence AnalysisAdd
    BLAST
    Transmembranei411 – 43121HelicalSequence AnalysisAdd
    BLAST
    Transmembranei436 – 45621HelicalSequence AnalysisAdd
    BLAST
    Transmembranei487 – 50721HelicalSequence AnalysisAdd
    BLAST
    Transmembranei521 – 54121HelicalSequence AnalysisAdd
    BLAST
    Transmembranei592 – 61221HelicalSequence AnalysisAdd
    BLAST
    Transmembranei655 – 67521HelicalSequence AnalysisAdd
    BLAST
    Transmembranei681 – 69919HelicalSequence AnalysisAdd
    BLAST
    Transmembranei725 – 74521HelicalSequence AnalysisAdd
    BLAST
    Transmembranei900 – 92021HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi90 – 12233Ala-richAdd
    BLAST
    Compositional biasi188 – 1947Poly-Gly

    Sequence similaritiesi

    Belongs to the SLC12A transporter family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0531.
    HOGENOMiHOG000062855.
    HOVERGENiHBG052851.
    InParanoidiP55011.
    KOiK10951.
    OMAiHDAFDIQ.
    OrthoDBiEOG75MVVC.
    PhylomeDBiP55011.
    TreeFamiTF313191.

    Family and domain databases

    InterProiIPR004841. AA-permease/SLC12A_dom.
    IPR013612. AA_permease_N.
    IPR002443. Na/K/Cl_cotranspt.
    IPR002444. Na/K/Cl_cotranspt1.
    IPR004842. Na/K/Cl_cotransptS.
    [Graphical view]
    PfamiPF00324. AA_permease. 1 hit.
    PF08403. AA_permease_N. 1 hit.
    [Graphical view]
    PRINTSiPR01207. NAKCLTRNSPRT.
    PR01208. NAKCLTRSPRT1.
    TIGRFAMsiTIGR00930. 2a30. 1 hit.

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P55011-1) [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

    MEPRPTAPSS GAPGLAGVGE TPSAAALAAA RVELPGTAVP SVPEDAAPAS     50
    RDGGGVRDEG PAAAGDGLGR PLGPTPSQSR FQVDLVSENA GRAAAAAAAA 100
    AAAAAAAGAG AGAKQTPADG EASGESEPAK GSEEAKGRFR VNFVDPAASS 150
    SAEDSLSDAA GVGVDGPNVS FQNGGDTVLS EGSSLHSGGG GGSGHHQHYY 200
    YDTHTNTYYL RTFGHNTMDA VPRIDHYRHT AAQLGEKLLR PSLAELHDEL 250
    EKEPFEDGFA NGEESTPTRD AVVTYTAESK GVVKFGWIKG VLVRCMLNIW 300
    GVMLFIRLSW IVGQAGIGLS VLVIMMATVV TTITGLSTSA IATNGFVRGG 350
    GAYYLISRSL GPEFGGAIGL IFAFANAVAV AMYVVGFAET VVELLKEHSI 400
    LMIDEINDIR IIGAITVVIL LGISVAGMEW EAKAQIVLLV ILLLAIGDFV 450
    IGTFIPLESK KPKGFFGYKS EIFNENFGPD FREEETFFSV FAIFFPAATG 500
    ILAGANISGD LADPQSAIPK GTLLAILITT LVYVGIAVSV GSCVVRDATG 550
    NVNDTIVTEL TNCTSAACKL NFDFSSCESS PCSYGLMNNF QVMSMVSGFT 600
    PLISAGIFSA TLSSALASLV SAPKIFQALC KDNIYPAFQM FAKGYGKNNE 650
    PLRGYILTFL IALGFILIAE LNVIAPIISN FFLASYALIN FSVFHASLAK 700
    SPGWRPAFKY YNMWISLLGA ILCCIVMFVI NWWAALLTYV IVLGLYIYVT 750
    YKKPDVNWGS STQALTYLNA LQHSIRLSGV EDHVKNFRPQ CLVMTGAPNS 800
    RPALLHLVHD FTKNVGLMIC GHVHMGPRRQ AMKEMSIDQA KYQRWLIKNK 850
    MKAFYAPVHA DDLREGAQYL MQAAGLGRMK PNTLVLGFKK DWLQADMRDV 900
    DMYINLFHDA FDIQYGVVVI RLKEGLDISH LQGQEELLSS QEKSPGTKDV 950
    VVSVEYSKKS DLDTSKPLSE KPITHKVEEE DGKTATQPLL KKESKGPIVP 1000
    LNVADQKLLE ASTQFQKKQG KNTIDVWWLF DDGGLTLLIP YLLTTKKKWK 1050
    DCKIRVFIGG KINRIDHDRR AMATLLSKFR IDFSDIMVLG DINTKPKKEN 1100
    IIAFEEIIEP YRLHEDDKEQ DIADKMKEDE PWRITDNELE LYKTKTYRQI 1150
    RLNELLKEHS STANIIVMSL PVARKGAVSS ALYMAWLEAL SKDLPPILLV 1200
    RGNHQSVLTF YS 1212
    Length:1,212
    Mass (Da):131,447
    Last modified:October 1, 1996 - v1
    Checksum:iA6BF174ACCDA2EC1
    GO
    Isoform 2 (identifier: P55011-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         976-991: Missing.

    Show »
    Length:1,196
    Mass (Da):129,679
    Checksum:i651AF731842344AD
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei976 – 99116Missing in isoform 2. 1 PublicationVSP_006105Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U30246 mRNA. Translation: AAC50561.1.
    AF439152 mRNA. Translation: AAL32454.1.
    CCDSiCCDS4144.1. [P55011-1]
    CCDS58965.1. [P55011-3]
    PIRiA57187.
    RefSeqiNP_001037.1. NM_001046.2. [P55011-1]
    UniGeneiHs.162585.
    Hs.712970.

    Genome annotation databases

    EnsembliENST00000262461; ENSP00000262461; ENSG00000064651. [P55011-1]
    ENST00000343225; ENSP00000340878; ENSG00000064651. [P55011-3]
    GeneIDi6558.
    KEGGihsa:6558.
    UCSCiuc003kus.3. human. [P55011-1]
    uc010jdg.3. human. [P55011-3]

    Polymorphism databases

    DMDMi1709292.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U30246 mRNA. Translation: AAC50561.1 .
    AF439152 mRNA. Translation: AAL32454.1 .
    CCDSi CCDS4144.1. [P55011-1 ]
    CCDS58965.1. [P55011-3 ]
    PIRi A57187.
    RefSeqi NP_001037.1. NM_001046.2. [P55011-1 ]
    UniGenei Hs.162585.
    Hs.712970.

    3D structure databases

    ProteinModelPortali P55011.
    SMRi P55011. Positions 347-692.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 112447. 9 interactions.
    DIPi DIP-43979N.
    IntActi P55011. 4 interactions.
    MINTi MINT-5004359.
    STRINGi 9606.ENSP00000262461.

    Chemistry

    ChEMBLi CHEMBL1615383.
    DrugBanki DB00887. Bumetanide.
    DB00761. Potassium Chloride.
    GuidetoPHARMACOLOGYi 969.

    Protein family/group databases

    TCDBi 2.A.30.3.1. the cation-chloride cotransporter (ccc) family.

    PTM databases

    PhosphoSitei P55011.

    Polymorphism databases

    DMDMi 1709292.

    Proteomic databases

    MaxQBi P55011.
    PaxDbi P55011.
    PRIDEi P55011.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000262461 ; ENSP00000262461 ; ENSG00000064651 . [P55011-1 ]
    ENST00000343225 ; ENSP00000340878 ; ENSG00000064651 . [P55011-3 ]
    GeneIDi 6558.
    KEGGi hsa:6558.
    UCSCi uc003kus.3. human. [P55011-1 ]
    uc010jdg.3. human. [P55011-3 ]

    Organism-specific databases

    CTDi 6558.
    GeneCardsi GC05P127419.
    HGNCi HGNC:10911. SLC12A2.
    HPAi HPA020130.
    MIMi 600840. gene.
    neXtProti NX_P55011.
    PharmGKBi PA35806.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0531.
    HOGENOMi HOG000062855.
    HOVERGENi HBG052851.
    InParanoidi P55011.
    KOi K10951.
    OMAi HDAFDIQ.
    OrthoDBi EOG75MVVC.
    PhylomeDBi P55011.
    TreeFami TF313191.

    Enzyme and pathway databases

    Reactomei REACT_19315. Cation-coupled Chloride cotransporters.
    SignaLinki P55011.

    Miscellaneous databases

    ChiTaRSi SLC12A2. human.
    GenomeRNAii 6558.
    NextBioi 25519.
    PROi P55011.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P55011.
    Bgeei P55011.
    CleanExi HS_SLC12A2.
    Genevestigatori P55011.

    Family and domain databases

    InterProi IPR004841. AA-permease/SLC12A_dom.
    IPR013612. AA_permease_N.
    IPR002443. Na/K/Cl_cotranspt.
    IPR002444. Na/K/Cl_cotranspt1.
    IPR004842. Na/K/Cl_cotransptS.
    [Graphical view ]
    Pfami PF00324. AA_permease. 1 hit.
    PF08403. AA_permease_N. 1 hit.
    [Graphical view ]
    PRINTSi PR01207. NAKCLTRNSPRT.
    PR01208. NAKCLTRSPRT1.
    TIGRFAMsi TIGR00930. 2a30. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "Primary structure, functional expression, and chromosomal localization of the bumetanide-sensitive Na-K-Cl cotransporter in human colon."
      Payne J.A., Xu J.-C., Haas M., Lytle Y.C., Ward D., Forbush B. III
      J. Biol. Chem. 270:17977-17985(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Colon.
    2. "Quantitation of Na(+)-K(+)-2Cl(-) cotransport splice variants in human tissues using kinetic polymerase chain reaction."
      Vibat C.R., Holland M.J., Kang J.J., Putney L.K., O'Donnell M.E.
      Anal. Biochem. 298:218-230(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 740-1066 (ISOFORM 2).
      Tissue: Eye.
    3. "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
      Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
      J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    4. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-77 AND SER-79, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    5. Cited for: ENZYME REGULATION.
    6. "Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
      Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
      Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiS12A2_HUMAN
    AccessioniPrimary (citable) accession number: P55011
    Secondary accession number(s): Q8N713, Q8WWH7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: October 1, 1996
    Last modified: October 1, 2014
    This is version 132 of the entry and version 1 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

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

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

    External Data

    Dasty 3