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P48764

- SL9A3_HUMAN

UniProt

P48764 - SL9A3_HUMAN

Protein

Sodium/hydrogen exchanger 3

Gene

SLC9A3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 127 (01 Oct 2014)
      Sequence version 2 (24 Nov 2009)
      Previous versions | rss
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    Functioni

    Involved in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gradient. Plays an important role in signal transduction.

    GO - Molecular functioni

    1. PDZ domain binding Source: UniProtKB
    2. protein binding Source: UniProtKB
    3. sodium:proton antiporter activity Source: UniProtKB

    GO - Biological processi

    1. ion transport Source: Reactome
    2. regulation of pH Source: Ensembl
    3. sodium ion transmembrane transport Source: GOC
    4. transmembrane transport Source: Reactome

    Keywords - Biological processi

    Antiport, Ion transport, Sodium transport, Transport

    Keywords - Ligandi

    Sodium

    Enzyme and pathway databases

    ReactomeiREACT_19314. Sodium/Proton exchangers.

    Protein family/group databases

    TCDBi2.A.36.1.15. the monovalent cation:proton antiporter-1 (cpa1) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Sodium/hydrogen exchanger 3
    Alternative name(s):
    Na(+)/H(+) exchanger 3
    Short name:
    NHE-3
    Solute carrier family 9 member 3
    Gene namesi
    Name:SLC9A3
    Synonyms:NHE3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:11073. SLC9A3.

    Subcellular locationi

    Apical cell membrane 1 Publication; Multi-pass membrane protein 1 Publication
    Note: In intestinal epithelial cells, localizes to the ileal brush border. Phosphorylation at Ser-663 by SGK1 is associated with increased abundance at the cell membrane.

    GO - Cellular componenti

    1. apical plasma membrane Source: UniProtKB-SubCell
    2. brush border Source: UniProtKB
    3. brush border membrane Source: UniProtKB
    4. cell surface Source: UniProtKB
    5. extracellular vesicular exosome Source: UniProtKB
    6. integral component of membrane Source: UniProtKB-KW
    7. plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA316.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 834834Sodium/hydrogen exchanger 3PRO_0000052356Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi241 – 2411N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi326 – 3261N-linked (GlcNAc...)Sequence Analysis
    Modified residuei555 – 5551PhosphoserineBy similarity
    Modified residuei607 – 6071PhosphoserineBy similarity
    Modified residuei663 – 6631Phosphoserine; by SGK1By similarity

    Post-translational modificationi

    Phosphorylated by PKA, which inhibits activity. Phosphorylation at Ser-663 by SGK1 is associated with increased abundance at the cell membrane.By similarity

    Keywords - PTMi

    Glycoprotein, Phosphoprotein

    Proteomic databases

    PaxDbiP48764.
    PRIDEiP48764.

    PTM databases

    PhosphoSiteiP48764.

    Expressioni

    Gene expression databases

    ArrayExpressiP48764.
    BgeeiP48764.
    CleanExiHS_SLC9A3.
    GenevestigatoriP48764.

    Organism-specific databases

    HPAiHPA036493.
    HPA036669.

    Interactioni

    Subunit structurei

    Binds SLC9A3R1 and SLC9A3R2. Interacts with CHP1, CHP2 and SHANK2. Interacts with PDZK1 (via C-terminal PDZ domain) By similarity. Interacts with PDZD3 and interactions decrease in response to elevated calcium ion levels.By similarity1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    MAST2Q6P0Q82EBI-7816923,EBI-493777

    Protein-protein interaction databases

    BioGridi112440. 10 interactions.
    IntActiP48764. 1 interaction.
    MINTiMINT-1787470.
    STRINGi9606.ENSP00000264938.

    Structurei

    3D structure databases

    ProteinModelPortaliP48764.
    SMRiP48764. Positions 204-229, 294-321, 460-502, 608-666.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 1212CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini25 – 5430CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini74 – 796CytoplasmicSequence Analysis
    Topological domaini100 – 11213ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini134 – 1396CytoplasmicSequence Analysis
    Topological domaini161 – 18020ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini203 – 2108CytoplasmicSequence Analysis
    Topological domaini233 – 25220ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini275 – 29016CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini310 – 34031ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini363 – 3697CytoplasmicSequence Analysis
    Topological domaini391 – 40515ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini427 – 4359ExtracellularSequence Analysis
    Topological domaini457 – 834378CytoplasmicSequence AnalysisAdd
    BLAST

    Intramembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Intramembranei13 – 2412Name=A/M1Sequence AnalysisAdd
    BLAST
    Intramembranei55 – 7319Name=B/M2Sequence AnalysisAdd
    BLAST
    Intramembranei406 – 42621Name=LSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei80 – 9920Helical; Name=C/M3Sequence AnalysisAdd
    BLAST
    Transmembranei113 – 13321Helical; Name=D/M4Sequence AnalysisAdd
    BLAST
    Transmembranei140 – 16021Helical; Name=E/M5Sequence AnalysisAdd
    BLAST
    Transmembranei181 – 20222Helical; Name=F/M5ASequence AnalysisAdd
    BLAST
    Transmembranei211 – 23222Helical; Name=G/M5BSequence AnalysisAdd
    BLAST
    Transmembranei253 – 27422Helical; Name=H/M6Sequence AnalysisAdd
    BLAST
    Transmembranei291 – 30919Helical; Name=I/M7Sequence AnalysisAdd
    BLAST
    Transmembranei341 – 36222Helical; Name=J/M8Sequence AnalysisAdd
    BLAST
    Transmembranei370 – 39021Helical; Name=K/M9Sequence AnalysisAdd
    BLAST
    Transmembranei436 – 45621Helical; Name=M/M10Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni590 – 66778Interaction with PDZD3By similarityAdd
    BLAST

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0025.
    HOGENOMiHOG000247044.
    HOVERGENiHBG052615.
    InParanoidiP48764.
    KOiK12040.
    OMAiRDKWSNF.
    OrthoDBiEOG7KQ20Z.
    PhylomeDBiP48764.
    TreeFamiTF317212.

    Family and domain databases

    InterProiIPR006153. Cation/H_exchanger.
    IPR018422. Cation/H_exchanger_CPA1.
    IPR018410. Na/H_exchanger_3/5.
    IPR004709. NaH_exchanger.
    [Graphical view]
    PANTHERiPTHR10110. PTHR10110. 1 hit.
    PfamiPF00999. Na_H_Exchanger. 1 hit.
    [Graphical view]
    PRINTSiPR01084. NAHEXCHNGR.
    PR01087. NAHEXCHNGR3.
    TIGRFAMsiTIGR00840. b_cpa1. 1 hit.

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P48764-1) [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

    MWGLGARGPD RGLLLALALG GLARAGGVEV EPGGAHGESG GFQVVTFEWA    50
    HVQDPYVIAL WILVASLAKI GFHLSHKVTS VVPESALLIV LGLVLGGIVW 100
    AADHIASFTL TPTVFFFYLL PPIVLDAGYF MPNRLFFGNL GTILLYAVVG 150
    TVWNAATTGL SLYGVFLSGL MGDLQIGLLD FLLFGSLMAA VDPVAVLAVF 200
    EEVHVNEVLF IIVFGESLLN DAVTVVLYNV FESFVALGGD NVTGVDCVKG 250
    IVSFFVVSLG GTLVGVVFAF LLSLVTRFTK HVRIIEPGFV FIISYLSYLT 300
    SEMLSLSAIL AITFCGICCQ KYVKANISEQ SATTVRYTMK MLASSAETII 350
    FMFLGISAVN PFIWTWNTAF VLLTLVFISV YRAIGVVLQT WLLNRYRMVQ 400
    LEPIDQVVLS YGGLRGAVAF ALVVLLDGDK VKEKNLFVST TIIVVFFTVI 450
    FQGLTIKPLV QWLKVKRSEH REPRLNEKLH GRAFDHILSA IEDISGQIGH 500
    NYLRDKWSHF DRKFLSRVLM RRSAQKSRDR ILNVFHELNL KDAISYVAEG 550
    ERRGSLAFIR SPSTDNVVNV DFTPRSSTVE ASVSYLLREN VSAVCLDMQS 600
    LEQRRRSIRD AEDMVTHHTL QQYLYKPRQE YKHLYSRHEL TPTEDEKQDR 650
    EIFHRTMRKR LESFKSTKLG LNQNKKAAKL YKRERAQKRR NSSIPNGKLP 700
    MESPAQNFTI KEKDLELSDT EEPPNYDEEM SGGIEFLASV TKDTASDSPA 750
    GIDNPVFSPD EALDRSLLAR LPPWLSPGET VVPSQRARTQ IPYSPGTFCR 800
    LMPFRLSSKS VDSFLQADGP EERPPAALPE STHM 834
    Length:834
    Mass (Da):92,855
    Last modified:November 24, 2009 - v2
    Checksum:i3E7CE3267F6E86F7
    GO
    Isoform 2 (identifier: P48764-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         452-460: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:825
    Mass (Da):91,904
    Checksum:iAEFBDB9089FC18C9
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti799 – 7991C → R.2 Publications
    Corresponds to variant rs2247114 [ dbSNP | Ensembl ].
    VAR_060593

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei452 – 4609Missing in isoform 2. 1 PublicationVSP_053989

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U28043 mRNA. Translation: AAB48990.1.
    AC010442 Genomic DNA. No translation available.
    AC106772 Genomic DNA. No translation available.
    BC101669 mRNA. Translation: AAI01670.1.
    BC101671 mRNA. Translation: AAI01672.1.
    BC143328 mRNA. Translation: AAI43329.1.
    CCDSiCCDS3855.1. [P48764-1]
    CCDS64116.1. [P48764-2]
    PIRiB40205.
    RefSeqiNP_001271280.1. NM_001284351.1. [P48764-2]
    NP_004165.2. NM_004174.2. [P48764-1]
    UniGeneiHs.658120.

    Genome annotation databases

    EnsembliENST00000264938; ENSP00000264938; ENSG00000066230. [P48764-1]
    ENST00000514375; ENSP00000422983; ENSG00000066230. [P48764-2]
    GeneIDi6550.
    KEGGihsa:6550.
    UCSCiuc003jbe.2. human. [P48764-1]

    Polymorphism databases

    DMDMi269849652.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U28043 mRNA. Translation: AAB48990.1 .
    AC010442 Genomic DNA. No translation available.
    AC106772 Genomic DNA. No translation available.
    BC101669 mRNA. Translation: AAI01670.1 .
    BC101671 mRNA. Translation: AAI01672.1 .
    BC143328 mRNA. Translation: AAI43329.1 .
    CCDSi CCDS3855.1. [P48764-1 ]
    CCDS64116.1. [P48764-2 ]
    PIRi B40205.
    RefSeqi NP_001271280.1. NM_001284351.1. [P48764-2 ]
    NP_004165.2. NM_004174.2. [P48764-1 ]
    UniGenei Hs.658120.

    3D structure databases

    ProteinModelPortali P48764.
    SMRi P48764. Positions 204-229, 294-321, 460-502, 608-666.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 112440. 10 interactions.
    IntActi P48764. 1 interaction.
    MINTi MINT-1787470.
    STRINGi 9606.ENSP00000264938.

    Chemistry

    ChEMBLi CHEMBL3273.

    Protein family/group databases

    TCDBi 2.A.36.1.15. the monovalent cation:proton antiporter-1 (cpa1) family.

    PTM databases

    PhosphoSitei P48764.

    Polymorphism databases

    DMDMi 269849652.

    Proteomic databases

    PaxDbi P48764.
    PRIDEi P48764.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000264938 ; ENSP00000264938 ; ENSG00000066230 . [P48764-1 ]
    ENST00000514375 ; ENSP00000422983 ; ENSG00000066230 . [P48764-2 ]
    GeneIDi 6550.
    KEGGi hsa:6550.
    UCSCi uc003jbe.2. human. [P48764-1 ]

    Organism-specific databases

    CTDi 6550.
    GeneCardsi GC05M000473.
    H-InvDB HIX0004707.
    HIX0032039.
    HGNCi HGNC:11073. SLC9A3.
    HPAi HPA036493.
    HPA036669.
    MIMi 182307. gene.
    neXtProti NX_P48764.
    PharmGKBi PA316.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0025.
    HOGENOMi HOG000247044.
    HOVERGENi HBG052615.
    InParanoidi P48764.
    KOi K12040.
    OMAi RDKWSNF.
    OrthoDBi EOG7KQ20Z.
    PhylomeDBi P48764.
    TreeFami TF317212.

    Enzyme and pathway databases

    Reactomei REACT_19314. Sodium/Proton exchangers.

    Miscellaneous databases

    GeneWikii Sodium%E2%80%93hydrogen_antiporter_3.
    GenomeRNAii 6550.
    NextBioi 25493.
    PROi P48764.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P48764.
    Bgeei P48764.
    CleanExi HS_SLC9A3.
    Genevestigatori P48764.

    Family and domain databases

    InterProi IPR006153. Cation/H_exchanger.
    IPR018422. Cation/H_exchanger_CPA1.
    IPR018410. Na/H_exchanger_3/5.
    IPR004709. NaH_exchanger.
    [Graphical view ]
    PANTHERi PTHR10110. PTHR10110. 1 hit.
    Pfami PF00999. Na_H_Exchanger. 1 hit.
    [Graphical view ]
    PRINTSi PR01084. NAHEXCHNGR.
    PR01087. NAHEXCHNGR3.
    TIGRFAMsi TIGR00840. b_cpa1. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "Cloning, tissue distribution, and functional analysis of the human Na+/N+ exchanger isoform, NHE3."
      Brant S.R., Yun C.H., Donowitz M., Tse C.-M.
      Am. J. Physiol. 269:C198-C206(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ARG-799.
      Tissue: Kidney cortex.
    2. "The DNA sequence and comparative analysis of human chromosome 5."
      Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.
      , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
      Nature 431:268-274(2004) [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] (ISOFORMS 1 AND 2), VARIANT ARG-799.
      Tissue: Colon.
    4. "Elevated intracellular calcium stimulates NHE3 activity by an IKEPP (NHERF4) dependent mechanism."
      Zachos N.C., Hodson C., Kovbasnjuk O., Li X., Thelin W.R., Cha B., Milgram S., Donowitz M.
      Cell. Physiol. Biochem. 22:693-704(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PDZD3.

    Entry informationi

    Entry nameiSL9A3_HUMAN
    AccessioniPrimary (citable) accession number: P48764
    Secondary accession number(s): B7ZKR2, E9PF67, Q3MIW3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1996
    Last sequence update: November 24, 2009
    Last modified: October 1, 2014
    This is version 127 of the entry and version 2 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. 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