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Protein

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

Gene

SLC9A3R1

Organism
Oryctolagus cuniculus (Rabbit)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

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
Complete GO annotation...

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 Componenti: Unplaced

Subcellular locationi

  1. Cytoplasm By similarity
  2. Apical cell membrane By similarity
  3. Cell projectionfilopodium By similarity
  4. Cell projectionruffle By similarity
  5. Cell projectionmicrovillus By similarity
  6. Endomembrane system By similarity; Peripheral membrane protein By similarity

  7. 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
Complete GO annotation...

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.
InParanoidiQ28619.
KOiK13365.

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

« Hide

        10         20         30         40         50
MSADAAAGAP LPRLCCLEKG PNGYGFHLHG EKGKVGQYIR LVEPGSPAEK
60 70 80 90 100
AGLLAGDRLV EVNGENVEKE THQQVVSRIR AALNAVRLLV VDPDTDEQFR
110 120 130 140 150
KLGVQIRGEL LRAQAGPEQA GPPAAPGEQG PAGENEPREV EKSHPERREL
160 170 180 190 200
RPRLCAMKKG PNGYGFNLHS DKSRPGQFIR AVDPDSPAEA SGLREQDRIV
210 220 230 240 250
EVNGVCVEGK QHGDVVTAIK AGGDEAKLLV VDKETDEFFK KCKVVPSSEH
260 270 280 290 300
LNGPLPEPFT NGEIQKNNPE TLAPAASESP RPALARSASS DTSEELASQD
310 320 330 340 350
SPKKEDSTAP SSTSSSSDPI LDFSISLAVA KERAHQKRSS RRAPQMDWSE

KKELFSNL
Length:358
Mass (Da):38,562
Last modified:January 23, 2007 - v3
Checksum:iF55E6D6FFA01B991
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U19815 mRNA. Translation: AAA80218.1.
PIRiI46532.
RefSeqiNP_001075814.1. NM_001082345.1.
UniGeneiOcu.3088.

Genome annotation databases

GeneIDi100009196.
KEGGiocu:100009196.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U19815 mRNA. Translation: AAA80218.1.
PIRiI46532.
RefSeqiNP_001075814.1. NM_001082345.1.
UniGeneiOcu.3088.

3D structure databases

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

Protein-protein interaction databases

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

Proteomic databases

PRIDEiQ28619.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100009196.
KEGGiocu:100009196.

Organism-specific databases

CTDi9368.

Phylogenomic databases

HOVERGENiHBG052616.
InParanoidiQ28619.
KOiK13365.

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]
ProtoNetiSearch...

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: March 4, 2015
This is version 105 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.