P70441 (NHRF1_MOUSE) 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

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	355 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 By similarity. May participate in HTR4 targeting to microvilli. Ref.4
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 and CFTR. Binds ARHGAP17, EPI64, GNB2L1, OPRK1, GNAQ, CTNNB1, PLCB3 and CLCN3. Forms a complex with CFTR and SLC4A7. Forms a complex with SLC4A7 and ATP6V1B1 By similarity. Binds PDZK1. Binds the C-terminus of PAG1. In resting T-cells, part of a PAG1-SLC9A3R1-MSN complex which is disrupted upon TCR activation. Directly interacts with HTR4. Interacts with MCC 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. Ref.4 Ref.5 Ref.6 Ref.7
Subcellular location	Cytoplasm. Apical cell membrane. 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 By similarity. Translocates from the cytoplasm to the apical cell membrane in a PODXL-dependent manner. Ref.11
Sequence similarities	Contains 2 PDZ (DHR) domains.

Ontologies

Keywords
Biological process	Wnt signaling pathway
Cellular component	Cell membrane Cell projection Cytoplasm Membrane
Coding sequence diversity	Alternative splicing
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 actin cytoskeleton organization Inferred from mutant phenotype. Source: MGI activation of adenylate cyclase activity by dopamine receptor signaling pathway Inferred from mutant phenotype. Source: MGI activation of phospholipase C activity by dopamine receptor signaling pathway Inferred from mutant phenotype. Source: MGI bile acid secretion Inferred from mutant phenotype. Source: UniProtKB cellular phosphate ion homeostasis Inferred from mutant phenotype. Source: MGI cellular protein localization Inferred from mutant phenotype. Source: MGI glutathione transport Inferred from mutant phenotype. Source: UniProtKB negative regulation of cell migration Inferred from genetic interaction. Source: MGI negative regulation of phosphatidylinositol 3-kinase cascade Inferred from mutant phenotype. Source: UniProtKB negative regulation of platelet-derived growth factor receptor signaling pathway Inferred from mutant phenotype. Source: UniProtKB negative regulation of protein kinase B signaling cascade Inferred from mutant phenotype. Source: UniProtKB negative regulation of sodium ion transport Inferred from mutant phenotype. Source: MGI negative regulation of sodium:hydrogen antiporter activity Inferred from mutant phenotype. Source: MGI regulation of excretion Inferred from mutant phenotype. Source: MGI regulation of protein kinase activity Inferred from mutant phenotype. Source: UniProtKB renal absorption Inferred from mutant phenotype. Source: UniProtKB renal sodium ion transport Inferred from mutant phenotype. Source: MGI
Cellular component	apical plasma membrane Inferred from direct assay. Source: MGI brush border membrane Inferred from direct assay. Source: MGI 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 dopamine receptor binding Inferred from direct assay. Source: MGI phosphatase binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P70441-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P70441-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-317: Missing.
     318-318: L → M

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 355	354	Na(+)/H(+) exchange regulatory cofactor NHE-RF1		PRO_0000096800
Regions
	Domain	14 – 94	81	PDZ 1
	Domain	149 – 229	81	PDZ 2
Amino acid modifications
	Modified residue	2	1	N-acetylserine By similarity
	Modified residue	46	1	Phosphoserine By similarity
	Modified residue	275	1	Phosphoserine Ref.10
	Modified residue	283	1	Phosphoserine Ref.12 Ref.13
	Modified residue	285	1	Phosphoserine Ref.10 Ref.12
	Modified residue	286	1	Phosphoserine Ref.8 Ref.12
	Modified residue	288	1	Phosphothreonine By similarity
	Modified residue	289	1	Phosphoserine Ref.9 Ref.12
	Modified residue	297	1	Phosphoserine Ref.9 Ref.12
Natural variations
	Alternative sequence	1 – 317	317	Missing in isoform 2.		VSP_027877
	Alternative sequence	318	1	L → M in isoform 2.		VSP_027878

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 331F6BEE31DA0A11	FASTA	355	38,600
	10 20 30 40 50 60 MSADAAAGEP LPRLCCLEKG PNGYGFHLHG EKGKVGQFIR LVEPGSPAEK SGLLAGDRLV 70 80 90 100 110 120 EVNGENVEKE THQQVVSRIR AALNAVRLLV VDPETDERLK KLGVSIREEL LRPQEKSEQA 130 140 150 160 170 180 EPPAAADTHE AGDQNEAEKS HLRELRPRLC TMKKGPNGYG FNLHSDKSKP GQFIRAVDPD 190 200 210 220 230 240 SPAEASGLRA QDRIVEVNGV CMEGKQHGDV VSAIKGGGDE AKLLVVDKET DEFFKKCKVI 250 260 270 280 290 300 PSQEHLDGPL PEPFSNGEIQ KESSREALVE PASESPRPAL ARSASSDTSE ELNSQDSPKR 310 320 330 340 350 QVSTEPSSTS SSSSDPILDL NISLAVAKER AHQKRSSKRA PQMDWSKKNE LFSNL
	Isoform 2 [UniParc]. Checksum: 08D620869EE48A78	FASTA	38	4,429
	10 20 30 MDLNISLAVA KERAHQKRSS KRAPQMDWSK KNELFSNL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of the cDNA and promoter sequences for the mouse sodium-hydrogen exchanger regulatory factor." Weinman E.J., Steplock D., Zhang X., Akhter S., Shenolikar S. Biochim. Biophys. Acta 1447:71-76(1999) [PubMed: 10500246] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Strain: C57BL/6. Tissue: Kidney.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Strain: C57BL/6J. Tissue: Thymus.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: C57BL/6. Tissue: Brain.
[4]	"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: 9560162] [Abstract] Cited for: FUNCTION, INTERACTION WITH ADRB2.
[5]	"Negative regulation of immune synapse formation by anchoring lipid raft to cytoskeleton through Cbp-EBP50-ERM assembly." Itoh K., Sakakibara M., Yamasaki S., Takeuchi A., Arase H., Miyazaki M., Nakajima N., Okada M., Saito T. J. Immunol. 168:541-544(2002) [PubMed: 11777944] [Abstract] Cited for: INTERACTION WITH PAG1, IDENTIFICATION IN A COMPLEX WITH PAG1 AND MSN.
[6]	"PDZK1: I. a major scaffolder in brush borders of proximal tubular cells." Gisler S.M., Pribanic S., Bacic D., Forrer P., Gantenbein A., Sabourin L.A., Tsuji A., Zhao Z.-S., Manser E., Biber J., Murer H. Kidney Int. 64:1733-1745(2003) [PubMed: 14531806] [Abstract] Cited for: INTERACTION WITH PDZK1.
[7]	"New sorting nexin (SNX27) and NHERF specifically interact with the 5-HT4a receptor splice variant: roles in receptor targeting." Joubert L., Hanson B., Barthet G., Sebben M., Claeysen S., Hong W., Marin P., Dumuis A., Bockaert J. J. Cell Sci. 117:5367-5379(2004) [PubMed: 15466885] [Abstract] Cited for: INTERACTION WITH HTR4.
[8]	"Phosphoproteome analysis of mouse liver using immobilized metal affinity purification and linear ion trap mass spectrometry." Jin W.-H., Dai J., Zhou H., Xia Q.-C., Zou H.-F., Zeng R. Rapid Commun. Mass Spectrom. 18:2169-2176(2004) [PubMed: 15378723] [Abstract] Cited for: PHOSPHORYLATION AT SER-286.
[9]	"Protein phosphorylation and expression profiling by Yin-yang multidimensional liquid chromatography (Yin-yang MDLC) mass spectrometry." Dai J., Jin W.-H., Sheng Q.-H., Shieh C.-H., Wu J.-R., Zeng R. J. Proteome Res. 6:250-262(2007) [PubMed: 17203969] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-289 AND SER-297, MASS SPECTROMETRY. Tissue: Liver.
[10]	"Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse synaptosomal preparations." Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B., Panse C., Schlapbach R., Mansuy I.M. Mol. Cell. Proteomics 6:283-293(2007) [PubMed: 17114649] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-275 AND SER-285, MASS SPECTROMETRY. Tissue: Brain cortex.
[11]	"The CD34-related molecule podocalyxin is a potent inducer of microvillus formation." Nielsen J.S., Graves M.L., Chelliah S., Vogl A.W., Roskelley C.D., McNagny K.M. PLoS ONE 2:E237-E237(2007) [PubMed: 17311105] [Abstract] Cited for: SUBCELLULAR LOCATION.
[12]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed: 17242355] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-283; SER-285; SER-286; SER-289 AND SER-297, MASS SPECTROMETRY. Tissue: Liver.
[13]	"Specific phosphopeptide enrichment with immobilized titanium ion affinity chromatography adsorbent for phosphoproteome analysis." Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H. J. Proteome Res. 7:3957-3967(2008) [PubMed: 18630941] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-283, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U74079 mRNA. Translation: AAB17569.1. AK040371 mRNA. Translation: BAC30573.2. BC085141 mRNA. Translation: AAH85141.1.
IPI	IPI00109311. IPI00857737.
RefSeq	NP_036160.1. NM_012030.2.
UniGene	Mm.27842.
3D structure databases
ProteinModelPortal	P70441.
SMR	P70441. Positions 11-99, 145-355.
ModBase	Search...
Protein-protein interaction databases
IntAct	P70441. 2 interactions.
MINT	MINT-144615.
STRING	P70441.
PTM databases
PhosphoSite	P70441.
Proteomic databases
PRIDE	P70441.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000021077; ENSMUSP00000021077; ENSMUSG00000020733.
GeneID	26941.
KEGG	mmu:26941.
Organism-specific databases
CTD	9368.
MGI	MGI:1349482. Slc9a3r1.
Phylogenomic databases
eggNOG	roNOG05702.
HOGENOM	HBG714863.
HOVERGEN	HBG052616.
InParanoid	P70441.
OMA	LCAMKKG.
OrthoDB	EOG4ZS93M.
PhylomeDB	P70441.
Gene expression databases
ArrayExpress	P70441.
Bgee	P70441.
Genevestigator	P70441.
GermOnline	ENSMUSG00000020733. Mus musculus.
Family and domain databases
InterPro	IPR015098. EBP50_C-term. IPR017300. NaH_exchngr_reg_CF_NHE-RF. IPR001478. PDZ/DHR/GLGF. [Graphical view]
KO	K13365.
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...
Other
NextBio	304861.
PMAP-CutDB	P70441.
SOURCE	Search...

Entry information

Entry name

NHRF1_MOUSE

Accession

Primary (citable) accession number: P70441
Secondary accession number(s): Q8BYD8

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 2, 2004
Last sequence update:	January 23, 2007
Last modified:	November 16, 2011
This is version 108 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program