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Q28619 (NHRF1_RABIT) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:SLC9A3R1
Synonyms:NHERF, NHERF1
OrganismOryctolagus cuniculus (Rabbit) [Reference proteome]
Taxonomic identifier9986 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus

Protein attributes

Sequence length358 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.2 Ref.3

Subunit structure

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. Ref.2 Ref.3 Ref.4

Subcellular location

Cytoplasm By similarity. Apical cell membrane By similarity. Cell projectionfilopodium By similarity. Cell projectionruffle By similarity. Cell projectionmicrovillus By similarity. Endomembrane system; 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. Ref.2

Tissue specificity

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. Ref.1

Post-translational modification

Phosphorylated on serine residues. Ref.3

Sequence similarities

Contains 2 PDZ (DHR) domains.

Ontologies

Keywords
   Biological processWnt signaling pathway
   Cellular componentCell membrane
Cell projection
Cytoplasm
Membrane
   DomainRepeat
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

bile acid secretion

Inferred from sequence or structural similarity. Source: UniProtKB

glutathione transport

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell motility

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of phosphatidylinositol 3-kinase signaling

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of platelet-derived growth factor receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of protein kinase B signaling

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of protein kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

renal absorption

Inferred from sequence or structural similarity. Source: UniProtKB

renal phosphate ion absorption

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentapical plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

cell periphery

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

endomembrane system

Inferred from electronic annotation. Source: UniProtKB-SubCell

filopodium

Inferred from electronic annotation. Source: UniProtKB-SubCell

membrane

Inferred from sequence or structural similarity. Source: UniProtKB

microvillus

Inferred from sequence or structural similarity. Source: UniProtKB

microvillus membrane

Inferred from sequence or structural similarity. Source: UniProtKB

ruffle

Inferred from electronic annotation. Source: UniProtKB-SubCell

sperm midpiece

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionchloride channel regulator activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 10446210. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Grk6O70293-15EBI-7073613,EBI-7073604From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 358357Na(+)/H(+) exchange regulatory cofactor NHE-RF1
PRO_0000096801

Regions

Domain14 – 9481PDZ 1
Domain154 – 23481PDZ 2

Amino acid modifications

Modified residue21N-acetylserine By similarity
Modified residue461Phosphoserine By similarity
Modified residue2791Phosphoserine By similarity
Modified residue2891Phosphoserine Ref.3
Modified residue2901Phosphoserine Ref.3
Modified residue2921Phosphothreonine By similarity
Modified residue2931Phosphoserine By similarity
Modified residue3011Phosphoserine By similarity

Experimental info

Mutagenesis2871S → A: Abolishes phosphorylation; when associated with A-289 and A-290. Ref.3
Mutagenesis289 – 2902SS → AA: Abolishes phosphorylation; when associated with A-287. Ref.4
Mutagenesis2891S → D: Enhances dimerization. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Q28619 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: F55E6D6FFA01B991

FASTA35838,562
        10         20         30         40         50         60 
MSADAAAGAP LPRLCCLEKG PNGYGFHLHG EKGKVGQYIR LVEPGSPAEK AGLLAGDRLV 

        70         80         90        100        110        120 
EVNGENVEKE THQQVVSRIR AALNAVRLLV VDPDTDEQFR KLGVQIRGEL LRAQAGPEQA 

       130        140        150        160        170        180 
GPPAAPGEQG PAGENEPREV EKSHPERREL RPRLCAMKKG PNGYGFNLHS DKSRPGQFIR 

       190        200        210        220        230        240 
AVDPDSPAEA SGLREQDRIV EVNGVCVEGK QHGDVVTAIK AGGDEAKLLV VDKETDEFFK 

       250        260        270        280        290        300 
KCKVVPSSEH LNGPLPEPFT NGEIQKNNPE TLAPAASESP RPALARSASS DTSEELASQD 

       310        320        330        340        350 
SPKKEDSTAP SSTSSSSDPI LDFSISLAVA KERAHQKRSS RRAPQMDWSE KKELFSNL 

« Hide

References

[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U19815 mRNA. Translation: AAA80218.1.
PIRI46532.
RefSeqNP_001075814.1. NM_001082345.1.
UniGeneOcu.3088.

3D structure databases

ProteinModelPortalQ28619.
SMRQ28619. Positions 11-99, 150-236.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid1172218. 1 interaction.
IntActQ28619. 2 interactions.
MINTMINT-148118.

Proteomic databases

PRIDEQ28619.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID100009196.

Organism-specific databases

CTD9368.

Phylogenomic databases

HOVERGENHBG052616.

Family and domain databases

Gene3D2.30.42.10. 2 hits.
InterProIPR015098. EBP50_C-term.
IPR017300. NaH_exchngr_reg_CF_NHE-RF.
IPR001478. PDZ.
[Graphical view]
PfamPF09007. EBP50_C-term. 1 hit.
PF00595. PDZ. 2 hits.
[Graphical view]
PIRSFPIRSF037866. EBP50. 1 hit.
ProDomPD283022. EBP50_C-term. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00228. PDZ. 2 hits.
[Graphical view]
SUPFAMSSF50156. SSF50156. 2 hits.
PROSITEPS50106. PDZ. 2 hits.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameNHRF1_RABIT
AccessionPrimary (citable) accession number: Q28619
Entry history
Integrated into UniProtKB/Swiss-Prot: February 2, 2004
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 100 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families