Q28619 (NHRF1_RABIT) Reviewed, UniProtKB/Swiss-Prot
Last modified July 9, 2014. Version 100. History...
Names and origin
|Protein names||Recommended name:|
Na(+)/H(+) exchange regulatory cofactor NHE-RF1
Ezrin-radixin-moesin-binding phosphoprotein 50
Regulatory cofactor of Na(+)/H(+) exchanger
Sodium-hydrogen exchanger regulatory factor 1
Solute carrier family 9 isoform A3 regulatory factor 1
|Organism||Oryctolagus cuniculus (Rabbit) [Reference proteome]|
|Taxonomic identifier||9986 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus|
|Sequence length||358 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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
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
Cytoplasm By similarity. Apical cell membrane By similarity. Cell projection › filopodium By similarity. Cell projection › ruffle By similarity. Cell projection › microvillus 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
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
Phosphorylated on serine residues. Ref.3
Contains 2 PDZ (DHR) domains.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Initiator methionine||1||1||Removed By similarity|
|Chain||2 – 358||357||Na(+)/H(+) exchange regulatory cofactor NHE-RF1||PRO_0000096801|
|Domain||14 – 94||81||PDZ 1|
|Domain||154 – 234||81||PDZ 2|
Amino acid modifications
|Modified residue||2||1||N-acetylserine By similarity|
|Modified residue||46||1||Phosphoserine By similarity|
|Modified residue||279||1||Phosphoserine By similarity|
|Modified residue||289||1||Phosphoserine Ref.3|
|Modified residue||290||1||Phosphoserine Ref.3|
|Modified residue||292||1||Phosphothreonine By similarity|
|Modified residue||293||1||Phosphoserine By similarity|
|Modified residue||301||1||Phosphoserine By similarity|
|Mutagenesis||287||1||S → A: Abolishes phosphorylation; when associated with A-289 and A-290. Ref.3|
|Mutagenesis||289 – 290||2||SS → AA: Abolishes phosphorylation; when associated with A-287. Ref.4|
|Mutagenesis||289||1||S → D: Enhances dimerization. Ref.4|
|||"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.
|||"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.
|||"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.
|||"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.|
|U19815 mRNA. Translation: AAA80218.1.|
|RefSeq||NP_001075814.1. NM_001082345.1. |
3D structure databases
|SMR||Q28619. Positions 11-99, 150-236. |
Protein-protein interaction databases
|BioGrid||1172218. 1 interaction.|
|IntAct||Q28619. 2 interactions.|
Protocols and materials databases
Genome annotation databases
Family and domain databases
|Gene3D||22.214.171.124. 2 hits. |
|InterPro||IPR015098. EBP50_C-term. |
|Pfam||PF09007. EBP50_C-term. 1 hit. |
PF00595. PDZ. 2 hits.
|PIRSF||PIRSF037866. EBP50. 1 hit. |
|ProDom||PD283022. EBP50_C-term. 1 hit. |
[Graphical view] [Entries sharing at least one domain]
|SMART||SM00228. PDZ. 2 hits. |
|SUPFAM||SSF50156. SSF50156. 2 hits. |
|PROSITE||PS50106. PDZ. 2 hits. |
|Accession||Primary (citable) accession number: Q28619|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families