Q28619 (NHRF1_RABIT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	SLC9A3R1
Synonyms:	NHERF, NHERF1

Organism

Oryctolagus cuniculus (Rabbit) [Reference proteome]

Taxonomic identifier

9986 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus

Protein attributes

Sequence length	358 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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. 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. Ref.2 Ref.3 Ref.4
Subcellular location	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. 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 process	Wnt signaling pathway
Cellular component	Cell membrane Cell projection Cytoplasm Membrane
Domain	Repeat
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor 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 cascade 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 cascade Inferred from sequence or structural similarity. Source: UniProtKB regulation of protein kinase activity Inferred from sequence or structural similarity. Source: UniProtKB renal phosphate ion absorption Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	apical plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell 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 microvillus membrane Inferred from sequence or structural similarity. Source: UniProtKB ruffle Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	chloride channel regulator activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 358	357	Na(+)/H(+) exchange regulatory cofactor NHE-RF1		PRO_0000096801
Regions
	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	287	1	Phosphoserine By similarity
	Modified residue	289	1	Phosphoserine By similarity
	Modified residue	290	1	Phosphoserine By similarity
	Modified residue	292	1	Phosphothreonine By similarity
	Modified residue	293	1	Phosphoserine By similarity
	Modified residue	301	1	Phosphoserine By similarity
Experimental info
	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

Sequences

	Sequence		Length	Mass (Da)
	Q28619 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: F55E6D6FFA01B991	FASTA	358	38,562
	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

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.
[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.
PIR	I46532.
RefSeq	NP_001075814.1. NM_001082345.1.
UniGene	Ocu.3088.
3D structure databases
ProteinModelPortal	Q28619.
SMR	Q28619. Positions 11-99, 150-236.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-148118.
Proteomic databases
PRIDE	Q28619.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	100009196.
Organism-specific databases
CTD	9368.
Phylogenomic databases
HOVERGEN	HBG052616.
Family and domain databases
InterPro	IPR015098. EBP50_C-term. IPR017300. NaH_exchngr_reg_CF_NHE-RF. IPR001478. PDZ. [Graphical view]
Pfam	PF09007. EBP50_C-term. 1 hit. PF00595. PDZ. 2 hits. [Graphical view]
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. [Graphical view]
SUPFAM	SSF50156. PDZ. 2 hits.
PROSITE	PS50106. PDZ. 2 hits. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

NHRF1_RABIT

Accession

Primary (citable) accession number: Q28619

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 2, 2004
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 93 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program