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Q28619

- NHRF1_RABIT

UniProt

Q28619 - NHRF1_RABIT

Protein

Na(+)/H(+) exchange regulatory cofactor NHE-RF1

Gene

SLC9A3R1

Organism
Oryctolagus cuniculus (Rabbit)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 101 (01 Oct 2014)
      Sequence version 3 (23 Jan 2007)
      Previous versions | rss
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    Functioni

    Scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression. Necessary for recycling of internalized ADRB2. Was first known to play a role in the regulation of the activity and subcellular location of SLC9A3. Necessary for cAMP-mediated phosphorylation and inhibition of SLC9A3. Involved in sperm capacitation. May participate in the regulation of the chloride and bicarbonate homeostasis in spermatozoa. May enhance Wnt signaling. May participate in HTR4 targeting to microvilli By similarity. Involved in the regulation of phosphate reabsorption in the renal proximal tubules By similarity.By similarity

    GO - Molecular functioni

    1. chloride channel regulator activity Source: UniProtKB
    2. protein binding Source: IntAct

    GO - Biological processi

    1. bile acid secretion Source: UniProtKB
    2. glutathione transport Source: UniProtKB
    3. negative regulation of cell motility Source: UniProtKB
    4. negative regulation of phosphatidylinositol 3-kinase signaling Source: UniProtKB
    5. negative regulation of platelet-derived growth factor receptor signaling pathway Source: UniProtKB
    6. negative regulation of protein kinase B signaling Source: UniProtKB
    7. regulation of protein kinase activity Source: UniProtKB
    8. renal absorption Source: UniProtKB
    9. renal phosphate ion absorption Source: UniProtKB
    10. Wnt signaling pathway Source: UniProtKB-KW

    Keywords - Biological processi

    Wnt signaling pathway

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Na(+)/H(+) exchange regulatory cofactor NHE-RF1
    Short name:
    NHERF-1
    Alternative name(s):
    Ezrin-radixin-moesin-binding phosphoprotein 50
    Short name:
    EBP50
    Regulatory cofactor of Na(+)/H(+) exchanger
    Sodium-hydrogen exchanger regulatory factor 1
    Solute carrier family 9 isoform A3 regulatory factor 1
    Gene namesi
    Name:SLC9A3R1
    Synonyms:NHERF, NHERF1
    OrganismiOryctolagus cuniculus (Rabbit)
    Taxonomic identifieri9986 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
    ProteomesiUP000001811: Unplaced

    Subcellular locationi

    Cytoplasm By similarity. Apical cell membrane By similarity. Cell projectionfilopodium By similarity. Cell projectionruffle By similarity. Cell projectionmicrovillus By similarity. Endomembrane system By similarity; Peripheral membrane protein By similarity
    Note: Colocalizes with actin in microvilli-rich apical regions of the syncytiotrophoblast. Present in lipid rafts of T-cells. Translocates from the cytoplasm to the apical cell membrane in a PODXL-dependent manner By similarity. Colocalizes with CFTR at the midpiece of sperm tail By similarity.By similarity

    GO - Cellular componenti

    1. apical plasma membrane Source: UniProtKB-SubCell
    2. cell periphery Source: UniProtKB
    3. cytoplasm Source: UniProtKB
    4. endomembrane system Source: UniProtKB-SubCell
    5. filopodium Source: UniProtKB-SubCell
    6. membrane Source: UniProtKB
    7. microvillus Source: UniProtKB
    8. microvillus membrane Source: UniProtKB
    9. ruffle Source: UniProtKB-SubCell
    10. sperm midpiece Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Cell projection, Cytoplasm, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi287 – 2871S → A: Abolishes phosphorylation; when associated with A-289 and A-290. 1 Publication
    Mutagenesisi289 – 2902SS → AA: Abolishes phosphorylation; when associated with A-287. 1 Publication
    Mutagenesisi289 – 2891S → D: Enhances dimerization. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 358357Na(+)/H(+) exchange regulatory cofactor NHE-RF1PRO_0000096801Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylserineBy similarity
    Modified residuei46 – 461PhosphoserineBy similarity
    Modified residuei279 – 2791PhosphoserineBy similarity
    Modified residuei289 – 2891Phosphoserine1 Publication
    Modified residuei290 – 2901Phosphoserine1 Publication
    Modified residuei292 – 2921PhosphothreonineBy similarity
    Modified residuei293 – 2931PhosphoserineBy similarity
    Modified residuei301 – 3011PhosphoserineBy similarity

    Post-translational modificationi

    Phosphorylated on serine residues.1 Publication

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    PRIDEiQ28619.

    Expressioni

    Tissue specificityi

    Detected in ileum, duodenum and in kidney, where it is found in the glomerulus, the proximal tubule, the thick ascending limb of Henle's loop and the cortical collecting duct.1 Publication

    Interactioni

    Subunit structurei

    Homodimer, and heterodimer with SLC9A3R2. Binds the N-termini of EZR, RDX and MSN. Binds the C-termini of PDGFRA, PDGFRB, ADRB2, NOS2, CFTR and PAG1. In resting T-cells, part of a PAG1-SLC9A3R1-MSN complex which is disrupted upon TCR activation. Binds ARHGAP17, EPI64, GNB2L1, OPRK1, GNAQ, CTNNB1, PLCB3, PDZK1 and CLCN3. Forms a complex with CFTR and SLC4A7. Forms a complex with SLC4A7 and ATP6V1B1. Directly interacts with HTR4 By similarity. Interacts with TRPC4 (via the PDZ-binding domain) By similarity. Interacts (via the PDZ 1 domain) with PODXL (via the C-terminal PDZ-binding motif DTHL); interaction is not detected in glomerular epithelium cells By similarity. Interacts (via the PDZ 1 domain) with PODXL (via the C-terminal PDZ-binding motif DTHL); the interaction take place early in the secretory pathway and is necessary for its apical membrane sorting By similarity. Interacts with SLC34A1 By similarity. Interacts (via the PDZ domains) with SLC26A6 By similarity. Interacts with SLC26A3 By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Grk6O70293-15EBI-7073613,EBI-7073604From a different organism.

    Protein-protein interaction databases

    BioGridi1172218. 1 interaction.
    IntActiQ28619. 2 interactions.
    MINTiMINT-148118.

    Structurei

    3D structure databases

    ProteinModelPortaliQ28619.
    SMRiQ28619. Positions 11-99, 150-236.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini14 – 9481PDZ 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini154 – 23481PDZ 2PROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 2 PDZ (DHR) domains.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    HOVERGENiHBG052616.

    Family and domain databases

    Gene3Di2.30.42.10. 2 hits.
    InterProiIPR015098. EBP50_C-term.
    IPR017300. NaH_exchngr_reg_CF_NHE-RF.
    IPR001478. PDZ.
    [Graphical view]
    PfamiPF09007. EBP50_C-term. 1 hit.
    PF00595. PDZ. 2 hits.
    [Graphical view]
    PIRSFiPIRSF037866. EBP50. 1 hit.
    ProDomiPD283022. EBP50_C-term. 1 hit.
    [Graphical view] [Entries sharing at least one domain]
    SMARTiSM00228. PDZ. 2 hits.
    [Graphical view]
    SUPFAMiSSF50156. SSF50156. 2 hits.
    PROSITEiPS50106. PDZ. 2 hits.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q28619-1 [UniParc]FASTAAdd to Basket

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    MSADAAAGAP LPRLCCLEKG PNGYGFHLHG EKGKVGQYIR LVEPGSPAEK    50
    AGLLAGDRLV EVNGENVEKE THQQVVSRIR AALNAVRLLV VDPDTDEQFR 100
    KLGVQIRGEL LRAQAGPEQA GPPAAPGEQG PAGENEPREV EKSHPERREL 150
    RPRLCAMKKG PNGYGFNLHS DKSRPGQFIR AVDPDSPAEA SGLREQDRIV 200
    EVNGVCVEGK QHGDVVTAIK AGGDEAKLLV VDKETDEFFK KCKVVPSSEH 250
    LNGPLPEPFT NGEIQKNNPE TLAPAASESP RPALARSASS DTSEELASQD 300
    SPKKEDSTAP SSTSSSSDPI LDFSISLAVA KERAHQKRSS RRAPQMDWSE 350
    KKELFSNL 358
    Length:358
    Mass (Da):38,562
    Last modified:January 23, 2007 - v3
    Checksum:iF55E6D6FFA01B991
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U19815 mRNA. Translation: AAA80218.1.
    PIRiI46532.
    RefSeqiNP_001075814.1. NM_001082345.1.
    UniGeneiOcu.3088.

    Genome annotation databases

    GeneIDi100009196.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U19815 mRNA. Translation: AAA80218.1 .
    PIRi I46532.
    RefSeqi NP_001075814.1. NM_001082345.1.
    UniGenei Ocu.3088.

    3D structure databases

    ProteinModelPortali Q28619.
    SMRi Q28619. Positions 11-99, 150-236.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 1172218. 1 interaction.
    IntActi Q28619. 2 interactions.
    MINTi MINT-148118.

    Proteomic databases

    PRIDEi Q28619.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 100009196.

    Organism-specific databases

    CTDi 9368.

    Phylogenomic databases

    HOVERGENi HBG052616.

    Family and domain databases

    Gene3Di 2.30.42.10. 2 hits.
    InterProi IPR015098. EBP50_C-term.
    IPR017300. NaH_exchngr_reg_CF_NHE-RF.
    IPR001478. PDZ.
    [Graphical view ]
    Pfami PF09007. EBP50_C-term. 1 hit.
    PF00595. PDZ. 2 hits.
    [Graphical view ]
    PIRSFi PIRSF037866. EBP50. 1 hit.
    ProDomi PD283022. EBP50_C-term. 1 hit.
    [Graphical view ] [Entries sharing at least one domain ]
    SMARTi SM00228. PDZ. 2 hits.
    [Graphical view ]
    SUPFAMi SSF50156. SSF50156. 2 hits.
    PROSITEi PS50106. PDZ. 2 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Characterization of a protein cofactor that mediates protein kinase A regulation of the renal brush border membrane Na(+)-H+ exchanger."
      Weinman E.J., Steplock D., Wang Y., Shenolikar S.
      J. Clin. Invest. 95:2143-2149(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
      Strain: New Zealand white.
      Tissue: Kidney cortex.
    2. "The beta2-adrenergic receptor interacts with the Na+/H+-exchanger regulatory factor to control Na+/H+ exchange."
      Hall R.A., Premont R.T., Chow C.-W., Blitzer J.T., Pitcher J.A., Claing A., Stoffel R.H., Barak L.S., Shenolikar S., Weinman E.J., Grinstein S., Lefkowitz R.J.
      Nature 392:626-630(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SLC9A3 AND ADRB2.
    3. "cAMP-induced phosphorylation and inhibition of Na(+)/H(+) exchanger 3 (NHE3) are dependent on the presence but not the phosphorylation of NHE regulatory factor."
      Zizak M., Lamprecht G., Steplock D., Tariq N., Shenolikar S., Donowitz M., Yun C.H.C., Weinman E.J.
      J. Biol. Chem. 274:24753-24758(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH SLC9A3, MUTAGENESIS OF SER-287 AND 289-SER-SER-290, PHOSPHORYLATION AT SER-289 AND SER-290.
    4. "Oligomerization of NHERF-1 and NHERF-2 PDZ domains: differential regulation by association with receptor carboxyl-termini and by phosphorylation."
      Lau A.G., Hall R.A.
      Biochemistry 40:8572-8580(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: DIMERIZATION, INTERACTION WITH ADRB2, MUTAGENESIS OF SER-289.

    Entry informationi

    Entry nameiNHRF1_RABIT
    AccessioniPrimary (citable) accession number: Q28619
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 2, 2004
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 101 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3