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Protein

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

Gene

SLC9A3R1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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. May participate in HTR4 targeting to microvilli (By similarity). Involved in the regulation of phosphate reabsorption in the renal proximal tubules. Involved in sperm capacitation. May participate in the regulation of the chloride and bicarbonate homeostasis in spermatozoa.By similarity4 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processWnt signaling pathway

Enzyme and pathway databases

SignaLinkiO14745
SIGNORiO14745

Protein family/group databases

TCDBi8.A.24.1.1 the ezrin/radixin/moesin-binding phosphoprotein 50 (ebp50) family

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000109062.9
HGNCiHGNC:11075 SLC9A3R1
MIMi604990 gene
neXtProtiNX_O14745

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

Nephrolithiasis/osteoporosis, hypophosphatemic, 2 (NPHLOP2)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by decreased renal phosphate absorption, renal phosphate wasting, hypophosphatemia, hyperphosphaturia, hypercalciuria, nephrolithiasis and osteoporosis.
See also OMIM:612287
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06766168E → A in NPHLOP2; impairs the interaction with SLC34A1; causes a reduction of SLC34A1 amount on cell membrane and affects SLC34A1-dependent phosphate uptake. 1 PublicationCorresponds to variant dbSNP:rs139622189EnsemblClinVar.1
Natural variantiVAR_034899110L → V in NPHLOP2; the mutant expressed in cultured renal cells increases the generation of cyclic AMP (cAMP) by parathyroid hormone (PTH) and inhibits phosphate transport. 1 PublicationCorresponds to variant dbSNP:rs35910969EnsemblClinVar.1
Natural variantiVAR_048021153R → Q in NPHLOP2; the mutant expressed in cultured renal cells increases the generation of cAMP by PTH and inhibits phosphate transport. 1 PublicationCorresponds to variant dbSNP:rs41282065EnsemblClinVar.1
Natural variantiVAR_048022225E → K in NPHLOP2; the mutant expressed in cultured renal cells increases the generation of cAMP by PTH and inhibits phosphate transport. 1 PublicationCorresponds to variant dbSNP:rs119486097EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi355F → R: Loss of MSX binding. 1 Publication1
Mutagenesisi358Missing : Reduces MSX binding. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi9368
MalaCardsiSLC9A3R1
MIMi612287 phenotype
OpenTargetsiENSG00000109062
Orphaneti244305 Dominant hypophosphatemia with nephrolithiasis or osteoporosis
PharmGKBiPA35931

Polymorphism and mutation databases

BioMutaiSLC9A3R1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources2 Publications
ChainiPRO_00000967992 – 358Na(+)/H(+) exchange regulatory cofactor NHE-RF1Add BLAST357

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1 Publication1
Modified residuei2PhosphoserineCombined sources1
Modified residuei46PhosphoserineCombined sources1
Modified residuei162PhosphoserineCombined sources1
Modified residuei269PhosphoserineCombined sources1
Modified residuei280PhosphoserineCombined sources1
Modified residuei290PhosphoserineBy similarity1
Modified residuei291PhosphoserineBy similarity1
Modified residuei293PhosphothreonineBy similarity1
Modified residuei294PhosphoserineCombined sources1
Modified residuei299PhosphoserineBy similarity1
Modified residuei302PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated on serine residues.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO14745
MaxQBiO14745
PaxDbiO14745
PeptideAtlasiO14745
PRIDEiO14745
ProteomicsDBi48202

PTM databases

iPTMnetiO14745
PhosphoSitePlusiO14745

Expressioni

Tissue specificityi

Detected in liver, kidney, pancreas, prostate, spleen, small intestine and placenta, in particular in the syncytiotrophoblast.2 Publications

Inductioni

By estrogen.1 Publication

Gene expression databases

BgeeiENSG00000109062 Expressed in 217 organ(s), highest expression level in esophagus mucosa
CleanExiHS_SLC9A3R1
ExpressionAtlasiO14745 baseline and differential
GenevisibleiO14745 HS

Organism-specific databases

HPAiCAB001962
HPA009672
HPA027247

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, NOS2 and CFTR. Binds ARHGAP17, EPI64, RACK1, OPRK1, GNAQ, CTNNB1 and PLCB3. Binds PDZK1 (By similarity). Interacts with CLCN3. Binds the C-terminus of PAG1. In resting T-cells, part of a PAG1-SLC9A3R1-MSN complex which is disrupted upon TCR activation. Forms a complex with CFTR and SLC4A7. Forms a complex with SLC4A7 and ATP6V1B1. Interacts with TRPC4 (via the PDZ-binding domain). Directly interacts with HTR4 (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. 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 SLC26A3 (By similarity). Interacts with MCC. Interacts with SLC34A1. Interacts (via the PDZ domains) with SLC26A6 isoform 4 and isoform 5.By similarity22 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114769, 107 interactors
CORUMiO14745
DIPiDIP-29092N
ELMiO14745
IntActiO14745, 34 interactors
MINTiO14745
STRINGi9606.ENSP00000262613

Structurei

Secondary structure

1358
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO14745
SMRiO14745
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO14745

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini14 – 94PDZ 1PROSITE-ProRule annotationAdd BLAST81
Domaini154 – 234PDZ 2PROSITE-ProRule annotationAdd BLAST81

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410ITAB Eukaryota
ENOG4110SZZ LUCA
GeneTreeiENSGT00530000062999
HOGENOMiHOG000089940
HOVERGENiHBG052616
InParanoidiO14745
KOiK13365
OMAiLCAMKKG
OrthoDBiEOG091G086H
PhylomeDBiO14745
TreeFamiTF350449

Family and domain databases

InterProiView protein in InterPro
IPR015098 EBP50_C-term
IPR031199 NHERF-1
IPR017300 NHERF-1/NHERF-2
IPR001478 PDZ
IPR036034 PDZ_sf
PANTHERiPTHR14191:SF7 PTHR14191:SF7, 1 hit
PfamiView protein in Pfam
PF09007 EBP50_C, 1 hit
PF00595 PDZ, 2 hits
PIRSFiPIRSF037866 EBP50, 1 hit
ProDomiView protein in ProDom or Entries sharing at least one domain
PD283022 EBP50_C-term, 1 hit
SMARTiView protein in SMART
SM00228 PDZ, 2 hits
SUPFAMiSSF50156 SSF50156, 2 hits
PROSITEiView protein in PROSITE
PS50106 PDZ, 2 hits

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

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O14745-1) [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
MSADAAAGAP LPRLCCLEKG PNGYGFHLHG EKGKLGQYIR LVEPGSPAEK
60 70 80 90 100
AGLLAGDRLV EVNGENVEKE THQQVVSRIR AALNAVRLLV VDPETDEQLQ
110 120 130 140 150
KLGVQVREEL LRAQEAPGQA EPPAAAEVQG AGNENEPREA DKSHPEQREL
160 170 180 190 200
RPRLCTMKKG PSGYGFNLHS DKSKPGQFIR SVDPDSPAEA SGLRAQDRIV
210 220 230 240 250
EVNGVCMEGK QHGDVVSAIR AGGDETKLLV VDRETDEFFK KCRVIPSQEH
260 270 280 290 300
LNGPLPVPFT NGEIQKENSR EALAEAALES PRPALVRSAS SDTSEELNSQ
310 320 330 340 350
DSPPKQDSTA PSSTSSSDPI LDFNISLAMA KERAHQKRSS KRAPQMDWSK

KNELFSNL
Length:358
Mass (Da):38,868
Last modified:January 23, 2007 - v4
Checksum:iE33AF87016D37A65
GO
Isoform 2 (identifier: O14745-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-156: Missing.

Note: No experimental confirmation available.
Show »
Length:202
Mass (Da):22,034
Checksum:i544A8F15B453C859
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
J3QRP6J3QRP6_HUMAN
Na(+)/H(+) exchange regulatory cofa...
SLC9A3R1
215Annotation score:
J3QRA3J3QRA3_HUMAN
Na(+)/H(+) exchange regulatory cofa...
SLC9A3R1
35Annotation score:

Sequence cautioni

The sequence AAH49220 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06766168E → A in NPHLOP2; impairs the interaction with SLC34A1; causes a reduction of SLC34A1 amount on cell membrane and affects SLC34A1-dependent phosphate uptake. 1 PublicationCorresponds to variant dbSNP:rs139622189EnsemblClinVar.1
Natural variantiVAR_034899110L → V in NPHLOP2; the mutant expressed in cultured renal cells increases the generation of cyclic AMP (cAMP) by parathyroid hormone (PTH) and inhibits phosphate transport. 1 PublicationCorresponds to variant dbSNP:rs35910969EnsemblClinVar.1
Natural variantiVAR_048021153R → Q in NPHLOP2; the mutant expressed in cultured renal cells increases the generation of cAMP by PTH and inhibits phosphate transport. 1 PublicationCorresponds to variant dbSNP:rs41282065EnsemblClinVar.1
Natural variantiVAR_048022225E → K in NPHLOP2; the mutant expressed in cultured renal cells increases the generation of cAMP by PTH and inhibits phosphate transport. 1 PublicationCorresponds to variant dbSNP:rs119486097EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0554971 – 156Missing in isoform 2. 1 PublicationAdd BLAST156

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF015926 mRNA Translation: AAC52084.1
AF036241 mRNA Translation: AAC04572.1
AK128474 mRNA Translation: BAG54683.1
AC016888 Genomic DNA No translation available.
CH471099 Genomic DNA Translation: EAW89189.1
BC001443 mRNA Translation: AAH01443.1
BC003361 mRNA Translation: AAH03361.1
BC011777 mRNA Translation: AAH11777.1
BC049220 mRNA Translation: AAH49220.1 Different initiation.
BC053350 mRNA Translation: AAH53350.1
CCDSiCCDS11705.1 [O14745-1]
RefSeqiNP_004243.1, NM_004252.4 [O14745-1]
UniGeneiHs.724482
Hs.744126

Genome annotation databases

EnsembliENST00000262613; ENSP00000262613; ENSG00000109062 [O14745-1]
ENST00000413388; ENSP00000464982; ENSG00000109062 [O14745-2]
GeneIDi9368
KEGGihsa:9368
UCSCiuc002jlo.5 human [O14745-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF015926 mRNA Translation: AAC52084.1
AF036241 mRNA Translation: AAC04572.1
AK128474 mRNA Translation: BAG54683.1
AC016888 Genomic DNA No translation available.
CH471099 Genomic DNA Translation: EAW89189.1
BC001443 mRNA Translation: AAH01443.1
BC003361 mRNA Translation: AAH03361.1
BC011777 mRNA Translation: AAH11777.1
BC049220 mRNA Translation: AAH49220.1 Different initiation.
BC053350 mRNA Translation: AAH53350.1
CCDSiCCDS11705.1 [O14745-1]
RefSeqiNP_004243.1, NM_004252.4 [O14745-1]
UniGeneiHs.724482
Hs.744126

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1G9OX-ray1.50A11-99[»]
1GQ4X-ray1.90A11-94[»]
1GQ5X-ray2.20A11-94[»]
1I92X-ray1.70A11-94[»]
1SGHX-ray3.50B321-358[»]
2D10X-ray2.50E/F/G/H331-358[»]
2JXONMR-A150-240[»]
2KJDNMR-A150-270[»]
2KRGNMR-A150-358[»]
2M0TNMR-A11-120[»]
2M0UNMR-A11-120[»]
2M0VNMR-A150-270[»]
2OZFX-ray1.50A150-235[»]
4JL7X-ray1.16A11-95[»]
4LMMX-ray1.10A11-94[»]
4MPAX-ray1.10A11-94[»]
4N6XX-ray1.05A11-94[»]
4PQWX-ray1.47A11-94[»]
4Q3HX-ray1.44A/B150-234[»]
ProteinModelPortaliO14745
SMRiO14745
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114769, 107 interactors
CORUMiO14745
DIPiDIP-29092N
ELMiO14745
IntActiO14745, 34 interactors
MINTiO14745
STRINGi9606.ENSP00000262613

Protein family/group databases

TCDBi8.A.24.1.1 the ezrin/radixin/moesin-binding phosphoprotein 50 (ebp50) family

PTM databases

iPTMnetiO14745
PhosphoSitePlusiO14745

Polymorphism and mutation databases

BioMutaiSLC9A3R1

Proteomic databases

EPDiO14745
MaxQBiO14745
PaxDbiO14745
PeptideAtlasiO14745
PRIDEiO14745
ProteomicsDBi48202

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262613; ENSP00000262613; ENSG00000109062 [O14745-1]
ENST00000413388; ENSP00000464982; ENSG00000109062 [O14745-2]
GeneIDi9368
KEGGihsa:9368
UCSCiuc002jlo.5 human [O14745-1]

Organism-specific databases

CTDi9368
DisGeNETi9368
EuPathDBiHostDB:ENSG00000109062.9
GeneCardsiSLC9A3R1
HGNCiHGNC:11075 SLC9A3R1
HPAiCAB001962
HPA009672
HPA027247
MalaCardsiSLC9A3R1
MIMi604990 gene
612287 phenotype
neXtProtiNX_O14745
OpenTargetsiENSG00000109062
Orphaneti244305 Dominant hypophosphatemia with nephrolithiasis or osteoporosis
PharmGKBiPA35931
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410ITAB Eukaryota
ENOG4110SZZ LUCA
GeneTreeiENSGT00530000062999
HOGENOMiHOG000089940
HOVERGENiHBG052616
InParanoidiO14745
KOiK13365
OMAiLCAMKKG
OrthoDBiEOG091G086H
PhylomeDBiO14745
TreeFamiTF350449

Enzyme and pathway databases

SignaLinkiO14745
SIGNORiO14745

Miscellaneous databases

ChiTaRSiSLC9A3R1 human
EvolutionaryTraceiO14745
GeneWikiiSodium-hydrogen_antiporter_3_regulator_1
GenomeRNAii9368
PROiPR:O14745
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000109062 Expressed in 217 organ(s), highest expression level in esophagus mucosa
CleanExiHS_SLC9A3R1
ExpressionAtlasiO14745 baseline and differential
GenevisibleiO14745 HS

Family and domain databases

InterProiView protein in InterPro
IPR015098 EBP50_C-term
IPR031199 NHERF-1
IPR017300 NHERF-1/NHERF-2
IPR001478 PDZ
IPR036034 PDZ_sf
PANTHERiPTHR14191:SF7 PTHR14191:SF7, 1 hit
PfamiView protein in Pfam
PF09007 EBP50_C, 1 hit
PF00595 PDZ, 2 hits
PIRSFiPIRSF037866 EBP50, 1 hit
ProDomiView protein in ProDom or Entries sharing at least one domain
PD283022 EBP50_C-term, 1 hit
SMARTiView protein in SMART
SM00228 PDZ, 2 hits
SUPFAMiSSF50156 SSF50156, 2 hits
PROSITEiView protein in PROSITE
PS50106 PDZ, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiNHRF1_HUMAN
AccessioniPrimary (citable) accession number: O14745
Secondary accession number(s): B3KY21, O43552, Q86WQ5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 2, 2004
Last sequence update: January 23, 2007
Last modified: October 10, 2018
This is version 195 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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