Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P70441 (NHRF1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length355 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. May enhance Wnt signaling By similarity. May participate in HTR4 targeting to microvilli. Involved in the regulation of phosphate reabsorption in the renal proximal tubules By similarity. Involved in sperm capacitation. May participate in the regulation of the chloride and bicarbonate homeostasis in spermatozoa. Ref.4 Ref.13

Subunit structure

Homodimer, and heterodimer with SLC9A3R2. Binds the N-termini of EZR, RDX and MSN. Binds the C-termini of PDGFRA, PDGFRB, ADRB2 and NOS2. 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. Interacts with SLC34A1 By similarity. Interacts with CFTR, SLC26A3 and SLC26A6. Ref.4 Ref.5 Ref.6 Ref.7 Ref.13

Subcellular location

Cytoplasm. Apical cell membrane. 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 By similarity. Translocates from the cytoplasm to the apical cell membrane in a PODXL-dependent manner. Colocalizes with CFTR at the midpiece of sperm tail. Ref.9 Ref.13

Tissue specificity

Expressed in spermatogenic cells. Ref.13

Sequence similarities

Contains 2 PDZ (DHR) domains.

Ontologies

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

Inferred from electronic annotation. Source: UniProtKB-KW

actin cytoskeleton organization

Inferred from mutant phenotype PubMed 15591354. Source: MGI

adenylate cyclase-activating dopamine receptor signaling pathway

Inferred from mutant phenotype PubMed 20200151. Source: MGI

bile acid secretion

Inferred from mutant phenotype PubMed 20404332. Source: UniProtKB

cAMP-mediated signaling

Inferred from mutant phenotype PubMed 12586353. Source: MGI

cellular phosphate ion homeostasis

Inferred from mutant phenotype PubMed 12169661. Source: MGI

cellular protein localization

Inferred from mutant phenotype PubMed 12952857. Source: MGI

glutathione transport

Inferred from mutant phenotype PubMed 20404332. Source: UniProtKB

microvillus assembly

Inferred from electronic annotation. Source: Ensembl

negative regulation of ERK1 and ERK2 cascade

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell migration

Inferred from genetic interaction PubMed 16456542. Source: MGI

negative regulation of cell motility

Inferred from mutant phenotype PubMed 16456542. Source: UniProtKB

negative regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of phosphatidylinositol 3-kinase signaling

Inferred from mutant phenotype PubMed 16456542. Source: UniProtKB

negative regulation of platelet-derived growth factor receptor signaling pathway

Inferred from mutant phenotype PubMed 18190691. Source: UniProtKB

negative regulation of protein kinase B signaling

Inferred from mutant phenotype PubMed 18190691. Source: UniProtKB

negative regulation of sodium ion transport

Inferred from mutant phenotype PubMed 12586353. Source: MGI

negative regulation of sodium:proton antiporter activity

Inferred from mutant phenotype PubMed 12586353. Source: MGI

phospholipase C-activating dopamine receptor signaling pathway

Inferred from mutant phenotype PubMed 20200151. Source: MGI

positive regulation of intrinsic apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

regulation of excretion

Inferred from mutant phenotype PubMed 12952857PubMed 16249272. Source: MGI

regulation of protein kinase activity

Inferred from mutant phenotype PubMed 18190691. Source: UniProtKB

renal absorption

Inferred from mutant phenotype PubMed 12169661PubMed 16987995. Source: UniProtKB

renal phosphate ion absorption

Inferred from sequence or structural similarity. Source: UniProtKB

renal sodium ion transport

Inferred from mutant phenotype PubMed 12586353. Source: MGI

   Cellular_componentapical part of cell

Inferred from direct assay PubMed 14996907. Source: MGI

apical plasma membrane

Inferred from direct assay PubMed 12169661. Source: MGI

brush border membrane

Inferred from direct assay PubMed 15591354. Source: MGI

centrosome

Inferred from electronic annotation. Source: Ensembl

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

intracellular membrane-bounded organelle

Inferred from electronic annotation. Source: Ensembl

membrane

Inferred from direct assay PubMed 19857202Ref.13. Source: UniProtKB

membrane raft

Inferred from electronic annotation. Source: Ensembl

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 direct assay Ref.13. Source: UniProtKB

   Molecular_functionchloride channel regulator activity

Inferred from sequence or structural similarity. Source: UniProtKB

dopamine receptor binding

Inferred from direct assay PubMed 20200151. Source: MGI

phosphatase binding

Inferred from physical interaction PubMed 16456542PubMed 18190691. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.13. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CftrP263613EBI-1184085,EBI-6115317
Slc26a3Q9WVC82EBI-1184085,EBI-6895537
Slc26a6Q8CIW62EBI-1184085,EBI-6895517
Slc4a10Q80ZA5-33EBI-1184085,EBI-8613086From a different organism.

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:
     2-317: Missing.
     318-318: L → M
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 355354Na(+)/H(+) exchange regulatory cofactor NHE-RF1
PRO_0000096800

Regions

Domain14 – 9481PDZ 1
Domain149 – 22981PDZ 2

Amino acid modifications

Modified residue21N-acetylserine By similarity
Modified residue461Phosphoserine By similarity
Modified residue2641Phosphoserine By similarity
Modified residue2751Phosphoserine By similarity
Modified residue2851Phosphoserine By similarity
Modified residue2861Phosphoserine Ref.8
Modified residue2881Phosphothreonine By similarity
Modified residue2891Phosphoserine Ref.10
Modified residue2971Phosphoserine Ref.10

Natural variations

Alternative sequence2 – 317316Missing in isoform 2.
VSP_027877
Alternative sequence3181L → M in isoform 2.
VSP_027878

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 331F6BEE31DA0A11

FASTA35538,600
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 047F20869EE4EAE1
Show »

FASTA394,560

References

« Hide '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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-286.
[9]"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] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[10]"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-289 AND SER-297, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[11]"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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[12]"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry."
Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.
Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
[13]"Participation of the Cl-/HCO(3)- exchangers SLC26A3 and SLC26A6, the Cl- channel CFTR, and the regulatory factor SLC9A3R1 in mouse sperm capacitation."
Chavez J.C., Hernandez-Gonzalez E.O., Wertheimer E., Visconti P.E., Darszon A., Trevino C.L.
Biol. Reprod. 86:1-14(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CFTR; SLC26A3 AND SLC26A6, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
+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.
CCDSCCDS36370.1. [P70441-1]
RefSeqNP_036160.1. NM_012030.2. [P70441-1]
UniGeneMm.27842.

3D structure databases

ProteinModelPortalP70441.
SMRP70441. Positions 11-99, 145-355.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid205077. 4 interactions.
IntActP70441. 12 interactions.
MINTMINT-144615.

PTM databases

PhosphoSiteP70441.

Proteomic databases

MaxQBP70441.
PaxDbP70441.
PRIDEP70441.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000021077; ENSMUSP00000021077; ENSMUSG00000020733. [P70441-1]
GeneID26941.
KEGGmmu:26941.
UCSCuc007mgp.1. mouse. [P70441-1]

Organism-specific databases

CTD9368.
MGIMGI:1349482. Slc9a3r1.

Phylogenomic databases

eggNOGNOG321335.
HOGENOMHOG000089940.
HOVERGENHBG052616.
InParanoidP70441.
KOK13365.
OMAVEKETHQ.
OrthoDBEOG7R56T6.
PhylomeDBP70441.
TreeFamTF350449.

Gene expression databases

ArrayExpressP70441.
BgeeP70441.
GenevestigatorP70441.

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...

Other

NextBio304861.
PMAP-CutDBP70441.
PROP70441.
SOURCESearch...

Entry information

Entry nameNHRF1_MOUSE
AccessionPrimary (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: July 9, 2014
This is version 131 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

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot