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O14745 (NHRF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 153. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length358 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. 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. Ref.2 Ref.6 Ref.7 Ref.42

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 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 4and isoform 5 Ref.1 Ref.2 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.17 Ref.18 Ref.19 Ref.20 Ref.28 Ref.34 Ref.37

Subcellular location

Cytoplasm By similarity. Apical cell membrane By similarity. Endomembrane system; Peripheral membrane protein. Cell projectionfilopodium. Cell projectionruffle. Cell projectionmicrovillus. Note: Translocates from the cytoplasm to the apical cell membrane in a PODXL-dependent manner. Colocalizes with CFTR at the midpiece of sperm tail By similarity. Colocalizes with actin in microvilli-rich apical regions of the syncytiotrophoblast. Found in microvilli, ruffling membrane and filopodia of HeLa cells. Present in lipid rafts of T-cells. Ref.1 Ref.2 Ref.8

Tissue specificity

Detected in liver, kidney, pancreas, prostate, spleen, small intestine and placenta, in particular in the syncytiotrophoblast. Ref.1 Ref.6

Induction

By estrogen. Ref.16

Post-translational modification

Phosphorylated on serine residues. Ref.1

Involvement in disease

Nephrolithiasis/osteoporosis, hypophosphatemic, 2 (NPHLOP2) [MIM:612287]: A disease characterized by decreased renal phosphate absorption, renal phosphate wasting, hypophosphatemia, hyperphosphaturia, hypercalciuria, nephrolithiasis and osteoporosis.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.34 Ref.42

Sequence similarities

Contains 2 PDZ (DHR) domains.

Sequence caution

The sequence AAH49220.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Biological processWnt signaling pathway
   Cellular componentCell membrane
Cell projection
Cytoplasm
Membrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainRepeat
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

actin cytoskeleton organization

Inferred from electronic annotation. Source: Ensembl

adenylate cyclase-activating dopamine receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

bile acid secretion

Inferred from sequence or structural similarity. Source: UniProtKB

cellular phosphate ion homeostasis

Inferred from electronic annotation. Source: Ensembl

cellular protein localization

Inferred from electronic annotation. Source: Ensembl

glutathione transport

Inferred from sequence or structural similarity. Source: UniProtKB

microvillus assembly

Inferred from mutant phenotype PubMed 20937695. Source: UniProtKB

negative regulation of ERK1 and ERK2 cascade

Inferred from direct assay PubMed 20012548. Source: UniProtKB

negative regulation of cell migration

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell proliferation

Inferred from direct assay PubMed 20012548. Source: UniProtKB

negative regulation of phosphatidylinositol 3-kinase signaling

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

Inferred from mutant phenotype PubMed 20736378. Source: UniProtKB

negative regulation of sodium ion transport

Inferred from electronic annotation. Source: Ensembl

negative regulation of sodium:proton antiporter activity

Inferred from electronic annotation. Source: Ensembl

phospholipase C-activating dopamine receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of intrinsic apoptotic signaling pathway

Inferred from direct assay PubMed 20012548. Source: UniProtKB

protein complex assembly

Traceable author statement Ref.2. Source: ProtInc

regulation of excretion

Inferred from electronic annotation. Source: Ensembl

regulation of protein kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of sodium:proton antiporter activity

Non-traceable author statement PubMed 9560162. Source: UniProtKB

renal absorption

Inferred from sequence or structural similarity. Source: UniProtKB

renal phosphate ion absorption

Inferred from mutant phenotype Ref.42. Source: UniProtKB

renal sodium ion transport

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentactin cytoskeleton

Traceable author statement Ref.2. Source: ProtInc

apical plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

brush border membrane

Inferred from electronic annotation. Source: Ensembl

cell periphery

Inferred from direct assay PubMed 17895247. Source: UniProtKB

centrosome

Inferred from direct assay. Source: HPA

cytoplasm

Inferred from direct assay PubMed 17895247PubMed 20736378. Source: UniProtKB

endomembrane system

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 19199708PubMed 20458337PubMed 23376485. Source: UniProt

filopodium

Inferred from electronic annotation. Source: UniProtKB-SubCell

intracellular membrane-bounded organelle

Inferred from direct assay. Source: HPA

membrane

Inferred from direct assay PubMed 20736378. Source: UniProtKB

membrane raft

Inferred from electronic annotation. Source: Ensembl

microvillus

Inferred from direct assay PubMed 17242191. Source: UniProtKB

microvillus membrane

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from direct assay. Source: HPA

ruffle

Inferred from electronic annotation. Source: UniProtKB-SubCell

sperm midpiece

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionPDZ domain binding

Inferred from physical interaction PubMed 16236806. Source: UniProtKB

beta-2 adrenergic receptor binding

Inferred from physical interaction PubMed 9560162. Source: UniProtKB

beta-catenin binding

Inferred from physical interaction PubMed 17242191. Source: UniProtKB

chloride channel regulator activity

Inferred from direct assay PubMed 12881487. Source: UniProtKB

growth factor receptor binding

Inferred from physical interaction PubMed 17242191. Source: UniProtKB

phosphatase binding

Inferred from physical interaction PubMed 16456542. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.9Ref.18Ref.20PubMed 17242191PubMed 17895247Ref.28PubMed 20395446PubMed 20442317Ref.34. Source: UniProtKB

protein self-association

Inferred from direct assay PubMed 17242191. Source: UniProtKB

receptor binding

Inferred from physical interaction PubMed 16456542. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.4 Ref.5
Chain2 – 358357Na(+)/H(+) exchange regulatory cofactor NHE-RF1
PRO_0000096799

Regions

Domain14 – 9481PDZ 1
Domain154 – 23481PDZ 2

Amino acid modifications

Modified residue21N-acetylserine Ref.5 Ref.27 Ref.33 Ref.35
Modified residue461Phosphoserine Ref.30
Modified residue1621Phosphoserine Ref.32
Modified residue2691Phosphoserine Ref.32
Modified residue2801Phosphoserine Ref.21 Ref.22 Ref.23 Ref.25 Ref.30 Ref.32
Modified residue2901Phosphoserine
Modified residue2911Phosphoserine
Modified residue2931Phosphothreonine
Modified residue2941Phosphoserine By similarity
Modified residue3021Phosphoserine By similarity

Natural variations

Natural variant681E → A in NPHLOP2; impairs the interaction with SLC34A1; causes a reduction of SLC34A1 amount on cell membrane and affects SLC34A1-dependent phosphate uptake. Ref.34
Corresponds to variant rs139622189 [ dbSNP | Ensembl ].
VAR_067661
Natural variant1101L → 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. Ref.42
Corresponds to variant rs35910969 [ dbSNP | Ensembl ].
VAR_034899
Natural variant1531R → Q in NPHLOP2; the mutant expressed in cultured renal cells increases the generation of cAMP by PTH and inhibits phosphate transport. Ref.42
Corresponds to variant rs41282065 [ dbSNP | Ensembl ].
VAR_048021
Natural variant2251E → K in NPHLOP2; the mutant expressed in cultured renal cells increases the generation of cAMP by PTH and inhibits phosphate transport. Ref.42
Corresponds to variant rs119486097 [ dbSNP | Ensembl ].
VAR_048022

Experimental info

Mutagenesis3551F → R: Loss of MSX binding. Ref.39
Mutagenesis3581Missing: Reduces MSX binding. Ref.39

Secondary structure

........................................................ 358
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O14745 [UniParc].

Last modified January 23, 2007. Version 4.
Checksum: E33AF87016D37A65

FASTA35838,868
        10         20         30         40         50         60 
MSADAAAGAP LPRLCCLEKG PNGYGFHLHG EKGKLGQYIR LVEPGSPAEK AGLLAGDRLV 

        70         80         90        100        110        120 
EVNGENVEKE THQQVVSRIR AALNAVRLLV VDPETDEQLQ KLGVQVREEL LRAQEAPGQA 

       130        140        150        160        170        180 
EPPAAAEVQG AGNENEPREA DKSHPEQREL RPRLCTMKKG PSGYGFNLHS DKSKPGQFIR 

       190        200        210        220        230        240 
SVDPDSPAEA SGLRAQDRIV EVNGVCMEGK QHGDVVSAIR AGGDETKLLV VDRETDEFFK 

       250        260        270        280        290        300 
KCRVIPSQEH LNGPLPVPFT NGEIQKENSR EALAEAALES PRPALVRSAS SDTSEELNSQ 

       310        320        330        340        350 
DSPPKQDSTA PSSTSSSDPI LDFNISLAMA KERAHQKRSS KRAPQMDWSK KNELFSNL 

« Hide

References

« Hide 'large scale' references
[1]"Identification of EBP50: a PDZ-containing phosphoprotein that associates with members of the ezrin-radixin-moesin family."
Reczek D., Berryman M., Bretscher A.
J. Cell Biol. 139:169-179(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 19-32 AND 341-350, PHOSPHORYLATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH EZR AND MSN.
[2]"NHE-RF, a regulatory cofactor for Na(+)-H+ exchange, is a common interactor for merlin and ERM (MERM) proteins."
Murthy A., Gonzalez-Agosti C., Cordero E., Pinney D., Candia C., Solomon F., Gusella J., Ramesh V.
J. Biol. Chem. 273:1273-1276(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH EZR; RDX AND MSN.
Tissue: Fetal brain.
[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].
Tissue: Blood, Lymph, Pancreas and Placenta.
[4]"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides."
Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J.
Nat. Biotechnol. 21:566-569(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-13.
Tissue: Platelet.
[5]Bienvenut W.V., Kanor S., Tissot J.-D., Quadroni M.
Submitted (MAY-2006) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-12; 39-49 AND 89-100, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: T-cell.
[6]"cAMP-mediated inhibition of the epithelial brush border Na+/H+ exchanger, NHE3, requires an associated regulatory protein."
Yun C.H.C., Oh S., Zizak M., Steplock D., Tsao S., Tse C.-M., Weinman E.J., Donowitz M.
Proc. Natl. Acad. Sci. U.S.A. 94:3010-3015(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH SLC9A3, TISSUE SPECIFICITY.
[7]"A kinase-regulated PDZ-domain interaction controls endocytic sorting of the beta2-adrenergic receptor."
Cao T.T., Deacon H.W., Reczek D., Bretscher A., von Zastrow M.
Nature 401:286-290(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ADRB2.
[8]"Interaction between two adapter proteins, PAG and EBP50: a possible link between membrane rafts and actin cytoskeleton."
Brdickova N., Brdicka T., Andera L., Spicka J., Angelisova P., Milgram S.L., Horejsi V.
FEBS Lett. 507:133-136(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PAG1, SUBCELLULAR LOCATION.
[9]"Identification of EPI64, a TBC/rabGAP domain-containing microvillar protein that binds to the first PDZ domain of EBP50 and E3KARP."
Reczek D., Bretscher A.
J. Cell Biol. 153:191-206(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EPI64; ARHGAP17; PLCB3 AND EZR.
[10]"Protein kinase C epsilon-dependent regulation of cystic fibrosis transmembrane regulator involves binding to a receptor for activated C kinase (RACK1) and RACK1 binding to Na+/H+ exchange regulatory factor."
Liedtke C.M., Yun C.H.C., Kyle N., Wang D.
J. Biol. Chem. 277:22925-22933(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GNB2L1.
[11]"Ezrin-radixin-moesin-binding phosphoprotein-50/Na+/H+ exchanger regulatory factor (EBP50/NHERF) blocks U50,488H-induced down-regulation of the human kappa opioid receptor by enhancing its recycling rate."
Li J.-G., Chen C., Liu-Chen L.-Y.
J. Biol. Chem. 277:27545-27552(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH OPRK1.
[12]"Epithelial inducible nitric-oxide synthase is an apical EBP50-binding protein that directs vectorial nitric oxide output."
Glynne P.A., Darling K.E.A., Picot J., Evans T.J.
J. Biol. Chem. 277:33132-33138(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NOS2.
[13]"Regulation of GTP-binding protein alpha q (Galpha q) signaling by the ezrin-radixin-moesin-binding phosphoprotein-50 (EBP50)."
Rochdi M.D., Watier V., La Madeleine C., Nakata H., Kozasa T., Parent J.-L.
J. Biol. Chem. 277:40751-40759(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GNAQ.
[14]"The cystic fibrosis transmembrane conductance regulator interacts with and regulates the activity of the HCO3- salvage transporter human Na+-HCO3-cotransport isoform 3."
Park M., Ko S.B.H., Choi J.Y., Muallem G., Thomas P.J., Pushkin A., Lee M.-S., Kim J.Y., Lee M.G., Muallem S., Kurtz I.
J. Biol. Chem. 277:50503-50509(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SLC4A7 AND CFTR.
[15]"The PDZ-interacting domain of TRPC4 controls its localization and surface expression in HEK293 cells."
Mery L., Strauss B., Dufour J.F., Krause K.H., Hoth M.
J. Cell Sci. 115:3497-3508(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TRPC4.
[16]"Estrogen receptor inducibility of the human Na+/H+ exchanger regulatory factor/ezrin-radixin-moesin binding protein 50 (NHE-RF/EBP50) gene involving multiple half-estrogen response elements."
Ediger T.R., Park S.-E., Katzenellenbogen B.S.
Mol. Endocrinol. 16:1828-1839(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION BY ESTROGEN.
[17]"The COOH termini of NBC3 and the 56-kDa H+-ATPase subunit are PDZ motifs involved in their interaction."
Pushkin A., Abuladze N., Newman D., Muronets V., Sassani P., Tatishchev S., Kurtz I.
Am. J. Physiol. 284:C667-C673(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SLC4A7 AND ATP6V1B1.
[18]"Isoforms of SLC26A6 mediate anion transport and have functional PDZ interaction domains."
Lohi H., Lamprecht G., Markovich D., Heil A., Kujala M., Seidler U., Kere J.
Am. J. Physiol. 284:C769-C779(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SLC26A6.
[19]"EBP50, a beta-catenin-associating protein, enhances Wnt signaling and is over-expressed in hepatocellular carcinoma."
Shibata T., Chuma M., Kokubu A., Sakamoto M., Hirohashi S.
Hepatology 38:178-186(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CTNNB1.
[20]"The PDZ-binding chloride channel ClC-3B localizes to the Golgi and associates with cystic fibrosis transmembrane conductance regulator-interacting PDZ proteins."
Gentzsch M., Cui L., Mengos A., Chang X.-B., Chen J.-H., Riordan J.R.
J. Biol. Chem. 278:6440-6449(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CLCN3.
[21]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-280, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[22]"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra."
Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.
J. Proteome Res. 6:4150-4162(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-280, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[23]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-280, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[24]"Phosphorylation analysis of primary human T lymphocytes using sequential IMAC and titanium oxide enrichment."
Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.
J. Proteome Res. 7:5167-5176(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: T-cell.
[25]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-280, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Platelet.
[26]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[27]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[28]"MCC, a new interacting protein for Scrib, is required for cell migration in epithelial cells."
Arnaud C., Sebbagh M., Nola S., Audebert S., Bidaut G., Hermant A., Gayet O., Dusetti N.J., Ollendorff V., Santoni M.J., Borg J.P., Lecine P.
FEBS Lett. 583:2326-2332(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MCC.
[29]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[30]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-46 AND SER-280, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[31]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[32]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-162; SER-269 AND SER-280, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[33]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[34]"A new human NHERF1 mutation decreases renal phosphate transporter NPT2a expression by a PTH-independent mechanism."
Courbebaisse M., Leroy C., Bakouh N., Salaun C., Beck L., Grandchamp B., Planelles G., Hall R.A., Friedlander G., Prie D.
PLoS ONE 7:E34764-E34764(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SLC34A1, VARIANT NPHLOP2 ALA-68, CHARACTERIZATION OF VARIANT NPHLOP2 ALA-68.
[35]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[36]"Structural basis of the Na+/H+ exchanger regulatory factor PDZ1 interaction with the carboxyl-terminal region of the cystic fibrosis transmembrane conductance regulator."
Karthikeyan S., Leung T., Ladias J.A.A.
J. Biol. Chem. 276:19683-19686(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 11-99 IN COMPLEX WITH CFTR.
[37]"Crystal structure of the PDZ1 domain of human Na(+)/H(+) exchanger regulatory factor provides insights into the mechanism of carboxyl-terminal leucine recognition by class I PDZ domains."
Karthikeyan S., Leung T., Birrane G., Webster G., Ladias J.A.A.
J. Mol. Biol. 308:963-973(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 11-99, HOMODIMERIZATION.
[38]"Structural determinants of the Na+/H+ exchanger regulatory factor interaction with the beta 2 adrenergic and platelet-derived growth factor receptors."
Karthikeyan S., Leung T., Ladias J.A.A.
J. Biol. Chem. 277:18973-18978(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 11-99 IN COMPLEX WITH PDGFRA; PDGFRB OR ADRB2.
[39]"The EBP50-moesin interaction involves a binding site regulated by direct masking on the FERM domain."
Finnerty C.M., Chambers D., Ingraffea J., Faber H.R., Karplus P.A., Bretscher A.
J. Cell Sci. 117:1547-1552(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS) OF 321-358 IN COMPLEX WITH MSX, MUTAGENESIS OF PHE-355 AND LEU-358.
[40]"Structural basis for NHERF recognition by ERM proteins."
Terawaki S., Maesaki R., Hakoshima T.
Structure 14:777-789(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 331-358 IN COMPLEX WITH RDX.
[41]"The crystal structure of the 2nd PDZ domain of the human NHERF-1 (SLC9A3R1)."
Structural genomics consortium (SGC)
Submitted (MAR-2007) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 150-236.
[42]"NHERF1 mutations and responsiveness of renal parathyroid hormone."
Karim Z., Gerard B., Bakouh N., Alili R., Leroy C., Beck L., Silve C., Planelles G., Urena-Torres P., Grandchamp B., Friedlander G., Prie D.
N. Engl. J. Med. 359:1128-1135(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN RENAL PHOSPHATE ABSORPTION, VARIANTS NPHLOP2 VAL-110; GLN-153 AND LYS-225, CHARACTERIZATION OF VARIANTS NPHLOP2 VAL-110; GLN-153 AND LYS-225.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF015926 mRNA. Translation: AAC52084.1.
AF036241 mRNA. Translation: AAC04572.1.
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.
CCDSCCDS11705.1.
RefSeqNP_004243.1. NM_004252.4.
UniGeneHs.724482.
Hs.744126.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalO14745.
SMRO14745. Positions 11-120, 150-358.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114769. 90 interactions.
DIPDIP-29092N.
IntActO14745. 22 interactions.
MINTMINT-4998796.
STRING9606.ENSP00000262613.

Protein family/group databases

TCDB8.A.24.1.1. the ezrin/radixin/moesin-binding phosphoprotein 50 (ebp50) family.

PTM databases

PhosphoSiteO14745.

Proteomic databases

MaxQBO14745.
PaxDbO14745.
PeptideAtlasO14745.
PRIDEO14745.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262613; ENSP00000262613; ENSG00000109062.
GeneID9368.
KEGGhsa:9368.
UCSCuc002jlo.4. human.

Organism-specific databases

CTD9368.
GeneCardsGC17P072744.
HGNCHGNC:11075. SLC9A3R1.
HPACAB001962.
HPA009672.
HPA027247.
MIM604990. gene.
612287. phenotype.
neXtProtNX_O14745.
Orphanet244305. Dominant hypophosphatemia with nephrolithiasis or osteoporosis.
PharmGKBPA35931.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG321335.
HOGENOMHOG000089940.
HOVERGENHBG052616.
InParanoidO14745.
KOK13365.
OMAVEKETHQ.
PhylomeDBO14745.
TreeFamTF350449.

Enzyme and pathway databases

SignaLinkO14745.

Gene expression databases

ArrayExpressO14745.
BgeeO14745.
CleanExHS_SLC9A3R1.
GenevestigatorO14745.

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

ChiTaRSSLC9A3R1. human.
EvolutionaryTraceO14745.
GeneWikiSodium-hydrogen_antiporter_3_regulator_1.
GenomeRNAi9368.
NextBio35084.
PROO14745.
SOURCESearch...

Entry information

Entry nameNHRF1_HUMAN
AccessionPrimary (citable) accession number: O14745
Secondary accession number(s): O43552, Q86WQ5
Entry history
Integrated into UniProtKB/Swiss-Prot: February 2, 2004
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 153 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM