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P26434

- SL9A4_RAT

UniProt

P26434 - SL9A4_RAT

Protein

Sodium/hydrogen exchanger 4

Gene

Slc9a4

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 109 (01 Oct 2014)
      Sequence version 1 (01 Aug 1992)
      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. May play a specialized role in the kidney in rectifying cell volume in response to extreme fluctuations of hyperosmolar-stimulated cell shrinkage. Is relatively amiloride and ethylisopropylamiloride (EIPA) insensitive. Can be activated under conditions of hyperosmolar-induced cell shrinkage in a sustained intracellular acidification-dependence manner. Activated by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) in a sustained intracellular acidification-dependence manner. Affects potassium/proton exchange as well as sodium/proton and lithium/proton exchange. In basolateral cell membrane, participates in homeostatic control of intracellular pH, and may play a role in proton extrusion in order to achieve transepithelial HCO3- secretion. In apical cell membrane may be involved in mediating sodium absorption. Requires for normal levels of gastric acid secretion, secretory membrane development, parietal cell maturation and/or differentiation and at least secondarily for chief cell differentiation.3 Publications

    GO - Molecular functioni

    1. sodium:proton antiporter activity Source: InterPro

    GO - Biological processi

    1. regulation of pH Source: InterPro

    Keywords - Biological processi

    Antiport, Ion transport, Sodium transport, Transport

    Keywords - Ligandi

    Sodium

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Sodium/hydrogen exchanger 4
    Alternative name(s):
    Na(+)/H(+) exchanger 4
    Short name:
    NHE-4
    Solute carrier family 9 member 4
    Gene namesi
    Name:Slc9a4
    Synonyms:Nhe4
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi3721. Slc9a4.

    Subcellular locationi

    GO - Cellular componenti

    1. apical plasma membrane Source: UniProtKB-SubCell
    2. basolateral plasma membrane Source: UniProtKB-SubCell
    3. integral component of membrane Source: UniProtKB-KW

    Keywords - Cellular componenti

    Cell membrane, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 717717Sodium/hydrogen exchanger 4PRO_0000052359Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi342 – 3421N-linked (GlcNAc...)Sequence Analysis
    Cross-linki352 – 352Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity

    Post-translational modificationi

    May be phosphorylated.

    Keywords - PTMi

    Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiP26434.
    PRIDEiP26434.

    Expressioni

    Tissue specificityi

    Most abundant in stomach, followed by colon. Lesser amounts were found in kidney, liver, brain, uterus and skeletal muscle. Predominantly expressed in the inner segments of inner medullary collecting ducts (IMCD) in kidney. Highly expressed in the cavi amnoni fields of hippocampus. Expressed in pancreas. Expressed in multiple nephron segments including proximla tubules, medullar thick ascending limbs (MTAL), cortical thick ascending limbs (CTAL), distal covoluted tubules and cortical and medullary collecting ducts. Expressed in submandibular gland.9 Publications

    Gene expression databases

    GenevestigatoriP26434.

    Interactioni

    Subunit structurei

    Interacts with CHP1 and CHP2.1 Publication

    Protein-protein interaction databases

    IntActiP26434. 2 interactions.
    STRINGi10116.ENSRNOP00000020716.

    Structurei

    3D structure databases

    ProteinModelPortaliP26434.
    SMRiP26434. Positions 124-150, 219-244.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 1313CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini29 – 6941CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini91 – 944CytoplasmicSequence Analysis
    Topological domaini115 – 12713ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini149 – 1546CytoplasmicSequence Analysis
    Topological domaini176 – 19116ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini217 – 2259CytoplasmicSequence Analysis
    Topological domaini248 – 26922ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini291 – 30414CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini326 – 35631ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini378 – 3847CytoplasmicSequence Analysis
    Topological domaini406 – 42015ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini442 – 4509ExtracellularSequence Analysis
    Topological domaini472 – 717246CytoplasmicSequence AnalysisAdd
    BLAST

    Intramembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Intramembranei14 – 2815Name=A/M1Sequence AnalysisAdd
    BLAST
    Intramembranei70 – 9021Name=B/M2Sequence AnalysisAdd
    BLAST
    Intramembranei421 – 44121Name=LSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei95 – 11420Helical; Name=C/M3Sequence AnalysisAdd
    BLAST
    Transmembranei128 – 14821Helical; Name=D/M4Sequence AnalysisAdd
    BLAST
    Transmembranei155 – 17521Helical; Name=E/M5Sequence AnalysisAdd
    BLAST
    Transmembranei192 – 21625Helical; Name=F/M5ASequence AnalysisAdd
    BLAST
    Transmembranei226 – 24722Helical; Name=G/M5BSequence AnalysisAdd
    BLAST
    Transmembranei270 – 29021Helical; Name=H/M6Sequence AnalysisAdd
    BLAST
    Transmembranei305 – 32521Helical; Name=I/M7Sequence AnalysisAdd
    BLAST
    Transmembranei357 – 37721Helical; Name=J/M8Sequence AnalysisAdd
    BLAST
    Transmembranei385 – 40521Helical; Name=K/M9Sequence AnalysisAdd
    BLAST
    Transmembranei451 – 47121Helical; Name=M/M10Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0025.
    HOGENOMiHOG000247044.
    HOVERGENiHBG052615.
    InParanoidiP26434.
    KOiK13961.

    Family and domain databases

    InterProiIPR006153. Cation/H_exchanger.
    IPR018422. Cation/H_exchanger_CPA1.
    IPR001953. Na/H_exchanger_2.
    IPR004709. NaH_exchanger.
    [Graphical view]
    PANTHERiPTHR10110. PTHR10110. 1 hit.
    PfamiPF00999. Na_H_Exchanger. 1 hit.
    [Graphical view]
    PRINTSiPR01084. NAHEXCHNGR.
    PR01086. NAHEXCHNGR2.
    TIGRFAMsiTIGR00840. b_cpa1. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    P26434-1 [UniParc]FASTAAdd to Basket

    « Hide

    MGPAMLRAFS SWKWLLLLMV LTCLEASSYV NESSSPTGQQ TPDARFAASS    50
    SDPDERISVF ELDYDYVQIP YEVTLWILLA SLAKIGFHLY HRLPHLMPES 100
    CLLIIVGALV GSIIFGTHHK SPPVMDSSIY FLYLLPPIVL ESGYFMPTRP 150
    FFENIGSILW WAGLGALINA FGIGLSLYFI CQIKAFGLGD INLLQNLLFG 200
    SLISAVDPVA VLAVFEEARV NEQLYMMIFG EALLNDGISV VLYNILIAFT 250
    KMHKFEDIEA VDILAGCARF VIVGCGGVFF GIIFGFISAF ITRFTQNISA 300
    IEPLIVFMFS YLSYLAAETL YLSGILAITA CAVTMKKYVE ENVSQTSYTT 350
    IKYFMKMLSS VSETLIFIFM GVSTVGKNHE WNWAFVCFTL AFCQIWRAIS 400
    VFTLFYVSNQ FRTFPFSIKD QLIIFYSGVR GAGSFSLAFL LPLTLFPRKK 450
    LFVTATLVVT YFTVFFQGIT IGPLVRYLDV RKTNKKESIN EELHIRLMDH 500
    LKAGIEDVCG QWSHYQVRDK FKKFDHRYLR KILIRRNQPK SSIVSLYKKL 550
    EMKQAIEMAE TGLLSSVASP TPYQSERIQG IKRLSPEDVE SMRDILTRNM 600
    YQVRQRTLSY NKYNLKPQTS EKQAKEILIR RQNTLRESLR KGQSLPWVKP 650
    AGTKNFRYLS FPYSNPQPAR RGARAAESTG NPCCWLLHFL LCRAMVEKIW 700
    GPGGQETQPR LLCRNLN 717
    Length:717
    Mass (Da):81,522
    Last modified:August 1, 1992 - v1
    Checksum:i4EFBBEC7D7782753
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M85301 mRNA. Translation: AAA41703.1.
    PIRiC40204.
    RefSeqiNP_775121.1. NM_173098.1.
    UniGeneiRn.9707.

    Genome annotation databases

    GeneIDi24785.
    KEGGirno:24785.
    UCSCiRGD:3721. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M85301 mRNA. Translation: AAA41703.1 .
    PIRi C40204.
    RefSeqi NP_775121.1. NM_173098.1.
    UniGenei Rn.9707.

    3D structure databases

    ProteinModelPortali P26434.
    SMRi P26434. Positions 124-150, 219-244.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P26434. 2 interactions.
    STRINGi 10116.ENSRNOP00000020716.

    Proteomic databases

    PaxDbi P26434.
    PRIDEi P26434.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 24785.
    KEGGi rno:24785.
    UCSCi RGD:3721. rat.

    Organism-specific databases

    CTDi 389015.
    RGDi 3721. Slc9a4.

    Phylogenomic databases

    eggNOGi COG0025.
    HOGENOMi HOG000247044.
    HOVERGENi HBG052615.
    InParanoidi P26434.
    KOi K13961.

    Miscellaneous databases

    NextBioi 604404.
    PROi P26434.

    Gene expression databases

    Genevestigatori P26434.

    Family and domain databases

    InterProi IPR006153. Cation/H_exchanger.
    IPR018422. Cation/H_exchanger_CPA1.
    IPR001953. Na/H_exchanger_2.
    IPR004709. NaH_exchanger.
    [Graphical view ]
    PANTHERi PTHR10110. PTHR10110. 1 hit.
    Pfami PF00999. Na_H_Exchanger. 1 hit.
    [Graphical view ]
    PRINTSi PR01084. NAHEXCHNGR.
    PR01086. NAHEXCHNGR2.
    TIGRFAMsi TIGR00840. b_cpa1. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "Molecular cloning of putative members of the Na/H exchanger gene family. cDNA cloning, deduced amino acid sequence, and mRNA tissue expression of the rat Na/H exchanger NHE-1 and two structurally related proteins."
      Orlowski J., Kandasamy R.A., Shull G.E.
      J. Biol. Chem. 267:9331-9339(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
      Strain: Sprague-Dawley.
      Tissue: Stomach.
    2. "A unique sodium-hydrogen exchange isoform (NHE-4) of the inner medulla of the rat kidney is induced by hyperosmolarity."
      Bookstein C., Musch M.W., DePaoli A., Xie Y., Villereal M., Rao M.C., Chang E.B.
      J. Biol. Chem. 269:29704-29709(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, TISSUE SPECIFICITY, INDUCTION.
    3. "Characterization of the rat Na+/H+ exchanger isoform NHE4 and localization in rat hippocampus."
      Bookstein C., Musch M.W., DePaoli A., Xie Y., Rabenau K., Villereal M., Rao M.C., Chang E.B.
      Am. J. Physiol. 271:C1629-C1638(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, TISSUE SPECIFICITY.
    4. "Heterologous expression of rat NHE4: a highly amiloride-resistant Na+/H+ exchanger isoform."
      Chambrey R., Achard J.-M., Warnock D.G.
      Am. J. Physiol. 272:C90-C98(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    5. "Tissue distribution of Na+/H+ exchanger isoforms NHE2 and NHE4 in rat intestine and kidney."
      Bookstein C., Xie Y., Rabenau K., Musch M.W., McSwine R.L., Rao M.C., Chang E.B.
      Am. J. Physiol. 273:C1496-C1505(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    6. "Immunochemical characterization of Na+/H+ exchanger isoform NHE4."
      Pizzonia J.H., Biemesderfer D., Abu-Alfa A.K., Wu M.-S., Exner M., Isenring P., Igarashi P., Aronson P.S.
      Am. J. Physiol. 275:F510-F517(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    7. "Expression of NHE1 and NHE4 in rat pancreatic zymogen granule membranes."
      Anderie I., Blum R., Haase W., Grinstein S., Thevenod F.
      Biochem. Biophys. Res. Commun. 246:330-336(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    8. "Expression of Na+/H+ exchanger isoforms in inner segment of inner medullary collecting duct."
      Sun A.M., Liu Y., Centracchio J., Dworkin L.D.
      J. Membr. Biol. 164:293-300(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    9. "Localization and functional characterization of Na+/H+ exchanger isoform NHE4 in rat thick ascending limbs."
      Chambrey R., St John P.L., Eladari D., Quentin F., Warnock D.G., Abrahamson D.R., Podevin R.-A., Paillard M.
      Am. J. Physiol. 281:F707-F717(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    10. "Calcineurin homologous protein isoform 2 (CHP2), Na+/H+ exchangers-binding protein, is expressed in intestinal epithelium."
      Inoue H., Nakamura Y., Nagita M., Takai T., Masuda M., Nakamura N., Kanazawa H.
      Biol. Pharm. Bull. 26:148-155(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CHP1 AND CHP2.
    11. "Na(+)/H(+) exchanger isoforms are differentially regulated in rat submandibular gland during acid/base disturbances in vivo."
      Oehlke O., Sprysch P., Rickmann M., Roussa E.
      Cell Tissue Res. 323:253-262(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiSL9A4_RAT
    AccessioniPrimary (citable) accession number: P26434
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1992
    Last sequence update: August 1, 1992
    Last modified: October 1, 2014
    This is version 109 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Caution

    The number, localization and denomination of hydrophobic domains in the Na+/H+ exchangers vary among authors.Curated

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3