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Protein

Na(+)/H(+) exchange regulatory cofactor NHE-RF1

Gene

Slc9a3r1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.By similarity2 Publications

GO - Molecular functioni

GO - Biological processi

  • actin cytoskeleton organization Source: MGI
  • adenylate cyclase-activating dopamine receptor signaling pathway Source: MGI
  • auditory receptor cell stereocilium organization Source: MGI
  • bile acid secretion Source: UniProtKB
  • cAMP-mediated signaling Source: MGI
  • cellular phosphate ion homeostasis Source: MGI
  • cellular protein localization Source: MGI
  • establishment of epithelial cell apical/basal polarity Source: MGI
  • establishment of Golgi localization Source: MGI
  • establishment of nucleus localization Source: MGI
  • establishment of protein localization to plasma membrane Source: MGI
  • gland morphogenesis Source: MGI
  • glutathione transport Source: UniProtKB
  • microvillus assembly Source: MGI
  • negative regulation of catenin import into nucleus Source: MGI
  • negative regulation of cell migration Source: MGI
  • negative regulation of cell motility Source: UniProtKB
  • negative regulation of cell proliferation Source: MGI
  • negative regulation of ERK1 and ERK2 cascade Source: MGI
  • negative regulation of mitotic cell cycle Source: MGI
  • negative regulation of phosphatidylinositol 3-kinase signaling Source: UniProtKB
  • negative regulation of platelet-derived growth factor receptor signaling pathway Source: UniProtKB
  • negative regulation of protein kinase B signaling Source: UniProtKB
  • negative regulation of sodium:proton antiporter activity Source: MGI
  • negative regulation of sodium ion transport Source: MGI
  • phospholipase C-activating dopamine receptor signaling pathway Source: MGI
  • positive regulation of intrinsic apoptotic signaling pathway Source: MGI
  • regulation of cell shape Source: MGI
  • regulation of cell size Source: MGI
  • regulation of excretion Source: MGI
  • regulation of protein kinase activity Source: UniProtKB
  • renal absorption Source: UniProtKB
  • renal phosphate ion absorption Source: UniProtKB
  • renal sodium ion transport Source: MGI
  • sensory perception of sound Source: MGI
  • Wnt signaling pathway Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Wnt signaling pathway

Names & Taxonomyi

Protein namesi
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 namesi
Name:Slc9a3r1
Synonyms:Nherf, Nherf1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1349482. Slc9a3r1.

Subcellular locationi

GO - Cellular componenti

  • apical part of cell Source: MGI
  • apical plasma membrane Source: MGI
  • brush border membrane Source: MGI
  • cell periphery Source: MGI
  • centrosome Source: MGI
  • cytoplasm Source: UniProtKB
  • endomembrane system Source: UniProtKB-SubCell
  • extracellular exosome Source: MGI
  • filopodium Source: UniProtKB-SubCell
  • intracellular membrane-bounded organelle Source: MGI
  • membrane Source: UniProtKB
  • membrane raft Source: Ensembl
  • microvillus Source: UniProtKB
  • microvillus membrane Source: UniProtKB
  • perinuclear region of cytoplasm Source: MGI
  • plasma membrane Source: MGI
  • ruffle Source: UniProtKB-SubCell
  • sperm midpiece Source: UniProtKB
  • stereocilium Source: MGI
  • stereocilium tip Source: MGI
  • vesicle Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000968002 – 355Na(+)/H(+) exchange regulatory cofactor NHE-RF1Add BLAST354

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineBy similarity1
Modified residuei2PhosphoserineBy similarity1
Modified residuei46PhosphoserineBy similarity1
Modified residuei264PhosphoserineBy similarity1
Modified residuei275PhosphoserineBy similarity1
Modified residuei285PhosphoserineBy similarity1
Modified residuei286PhosphoserineCombined sources1 Publication1
Modified residuei288PhosphothreonineCombined sources1
Modified residuei289PhosphoserineCombined sources1
Modified residuei294PhosphoserineCombined sources1
Modified residuei297PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP70441.
PaxDbiP70441.
PeptideAtlasiP70441.
PRIDEiP70441.

PTM databases

iPTMnetiP70441.
PhosphoSitePlusiP70441.

Miscellaneous databases

PMAP-CutDBP70441.

Expressioni

Tissue specificityi

Expressed in spermatogenic cells.1 Publication

Gene expression databases

BgeeiENSMUSG00000020733.
ExpressionAtlasiP70441. baseline and differential.
GenevisibleiP70441. MM.

Interactioni

Subunit structurei

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, RACK1, 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.By similarity5 Publications

Binary interactionsi

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi205077. 4 interactors.
IntActiP70441. 12 interactors.
MINTiMINT-144615.
STRINGi10090.ENSMUSP00000021077.

Structurei

3D structure databases

ProteinModelPortaliP70441.
SMRiP70441.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini14 – 94PDZ 1PROSITE-ProRule annotationAdd BLAST81
Domaini149 – 229PDZ 2PROSITE-ProRule annotationAdd BLAST81

Sequence similaritiesi

Contains 2 PDZ (DHR) domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410ITAB. Eukaryota.
ENOG4110SZZ. LUCA.
GeneTreeiENSGT00530000062999.
HOGENOMiHOG000089940.
HOVERGENiHBG052616.
InParanoidiP70441.
KOiK13365.
OMAiAMKKGPN.
OrthoDBiEOG091G086H.
PhylomeDBiP70441.
TreeFamiTF350449.

Family and domain databases

Gene3Di2.30.42.10. 2 hits.
InterProiIPR015098. EBP50_C-term.
IPR031199. NHERF-1.
IPR017300. NHERF-1/NHERF-2.
IPR001478. PDZ.
[Graphical view]
PANTHERiPTHR14191:SF7. PTHR14191:SF7. 1 hit.
PfamiPF09007. EBP50_C. 1 hit.
PF00595. PDZ. 2 hits.
[Graphical view]
PIRSFiPIRSF037866. EBP50. 1 hit.
ProDomiPD283022. EBP50_C-term. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00228. PDZ. 2 hits.
[Graphical view]
SUPFAMiSSF50156. SSF50156. 2 hits.
PROSITEiPS50106. PDZ. 2 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P70441-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSADAAAGEP LPRLCCLEKG PNGYGFHLHG EKGKVGQFIR LVEPGSPAEK
60 70 80 90 100
SGLLAGDRLV EVNGENVEKE THQQVVSRIR AALNAVRLLV VDPETDERLK
110 120 130 140 150
KLGVSIREEL LRPQEKSEQA EPPAAADTHE AGDQNEAEKS HLRELRPRLC
160 170 180 190 200
TMKKGPNGYG FNLHSDKSKP GQFIRAVDPD SPAEASGLRA QDRIVEVNGV
210 220 230 240 250
CMEGKQHGDV VSAIKGGGDE AKLLVVDKET DEFFKKCKVI PSQEHLDGPL
260 270 280 290 300
PEPFSNGEIQ KESSREALVE PASESPRPAL ARSASSDTSE ELNSQDSPKR
310 320 330 340 350
QVSTEPSSTS SSSSDPILDL NISLAVAKER AHQKRSSKRA PQMDWSKKNE

LFSNL
Length:355
Mass (Da):38,600
Last modified:January 23, 2007 - v3
Checksum:i331F6BEE31DA0A11
GO
Isoform 2 (identifier: P70441-2) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:38
Mass (Da):4,429
Checksum:i08D620869EE48A78
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0278771 – 317Missing in isoform 2. 1 PublicationAdd BLAST317
Alternative sequenceiVSP_027878318L → M in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U74079 mRNA. Translation: AAB17569.1.
AK040371 mRNA. Translation: BAC30573.2.
BC085141 mRNA. Translation: AAH85141.1.
CCDSiCCDS36370.1. [P70441-1]
RefSeqiNP_036160.1. NM_012030.2. [P70441-1]
UniGeneiMm.27842.

Genome annotation databases

EnsembliENSMUST00000021077; ENSMUSP00000021077; ENSMUSG00000020733. [P70441-1]
GeneIDi26941.
KEGGimmu:26941.
UCSCiuc007mgp.1. mouse. [P70441-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U74079 mRNA. Translation: AAB17569.1.
AK040371 mRNA. Translation: BAC30573.2.
BC085141 mRNA. Translation: AAH85141.1.
CCDSiCCDS36370.1. [P70441-1]
RefSeqiNP_036160.1. NM_012030.2. [P70441-1]
UniGeneiMm.27842.

3D structure databases

ProteinModelPortaliP70441.
SMRiP70441.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi205077. 4 interactors.
IntActiP70441. 12 interactors.
MINTiMINT-144615.
STRINGi10090.ENSMUSP00000021077.

PTM databases

iPTMnetiP70441.
PhosphoSitePlusiP70441.

Proteomic databases

EPDiP70441.
PaxDbiP70441.
PeptideAtlasiP70441.
PRIDEiP70441.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000021077; ENSMUSP00000021077; ENSMUSG00000020733. [P70441-1]
GeneIDi26941.
KEGGimmu:26941.
UCSCiuc007mgp.1. mouse. [P70441-1]

Organism-specific databases

CTDi9368.
MGIiMGI:1349482. Slc9a3r1.

Phylogenomic databases

eggNOGiENOG410ITAB. Eukaryota.
ENOG4110SZZ. LUCA.
GeneTreeiENSGT00530000062999.
HOGENOMiHOG000089940.
HOVERGENiHBG052616.
InParanoidiP70441.
KOiK13365.
OMAiAMKKGPN.
OrthoDBiEOG091G086H.
PhylomeDBiP70441.
TreeFamiTF350449.

Miscellaneous databases

PMAP-CutDBP70441.
PROiP70441.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000020733.
ExpressionAtlasiP70441. baseline and differential.
GenevisibleiP70441. MM.

Family and domain databases

Gene3Di2.30.42.10. 2 hits.
InterProiIPR015098. EBP50_C-term.
IPR031199. NHERF-1.
IPR017300. NHERF-1/NHERF-2.
IPR001478. PDZ.
[Graphical view]
PANTHERiPTHR14191:SF7. PTHR14191:SF7. 1 hit.
PfamiPF09007. EBP50_C. 1 hit.
PF00595. PDZ. 2 hits.
[Graphical view]
PIRSFiPIRSF037866. EBP50. 1 hit.
ProDomiPD283022. EBP50_C-term. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00228. PDZ. 2 hits.
[Graphical view]
SUPFAMiSSF50156. SSF50156. 2 hits.
PROSITEiPS50106. PDZ. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNHRF1_MOUSE
AccessioniPrimary (citable) accession number: P70441
Secondary accession number(s): Q8BYD8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 2, 2004
Last sequence update: January 23, 2007
Last modified: November 2, 2016
This is version 152 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.