O14745 (NHRF1_HUMAN) 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

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	358 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. May participate in HTR4 targeting to microvilli By similarity. Involved in the regulation of phosphate reabsorption in the renal proximal tubules. Ref.2 Ref.6 Ref.7 Ref.38
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 MCC. Interacts with SLC34A1. 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.26 Ref.31 Ref.33
Subcellular location	Cytoplasm By similarity. Apical cell membrane By similarity. Endomembrane system; Peripheral membrane protein. Cell projection › filopodium. Cell projection › ruffle. Cell projection › microvillus. Note: Translocates from the cytoplasm to the apical cell membrane in a PODXL-dependent manner 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.31 Ref.38
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 process	Wnt signaling pathway
Cellular component	Cell membrane Cell projection Cytoplasm Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Repeat
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW actin cytoskeleton organization Inferred from electronic annotation. Source: Compara adenylate cyclase-activating dopamine receptor signaling pathway Inferred from electronic annotation. Source: Compara apoptotic process Inferred from direct assay PubMed 20012548. Source: UniProtKB bile acid secretion Inferred from sequence or structural similarity. Source: UniProtKB cellular phosphate ion homeostasis Inferred from electronic annotation. Source: Compara cellular protein localization Inferred from electronic annotation. Source: Compara 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: Compara negative regulation of cell proliferation Inferred from direct assay PubMed 20012548. Source: UniProtKB negative regulation of phosphatidylinositol 3-kinase cascade 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 cascade Inferred from mutant phenotype PubMed 20736378. Source: UniProtKB negative regulation of sodium ion transport Inferred from electronic annotation. Source: Compara negative regulation of sodium:hydrogen antiporter activity Inferred from electronic annotation. Source: Compara phospholipase C-activating dopamine receptor signaling pathway Inferred from electronic annotation. Source: Compara protein complex assembly Traceable author statement Ref.2. Source: ProtInc regulation of excretion Inferred from electronic annotation. Source: Compara regulation of protein kinase activity Inferred from sequence or structural similarity. Source: UniProtKB regulation of sodium:hydrogen antiporter activity Non-traceable author statement PubMed 9560162. Source: UniProtKB renal phosphate ion absorption Inferred from mutant phenotype Ref.38. Source: UniProtKB renal sodium ion transport Inferred from electronic annotation. Source: Compara
Cellular_component	actin 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: Compara 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 filopodium Inferred from electronic annotation. Source: UniProtKB-SubCell intracellular membrane-bounded organelle Inferred from direct assay. Source: HPA 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 direct assay PubMed 12881487. Source: UniProtKB protein self-association Inferred from direct assay PubMed 17242191. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CFTR	P13569	2	EBI-349787,EBI-349854
MSN	P26038	5	EBI-349787,EBI-528768
NF2	P35240-1	4	EBI-349787,EBI-1014500

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.4 Ref.5

Chain

2 – 358

357

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

PRO_0000096799

Regions

Domain

14 – 94

81

PDZ 1

Domain

154 – 234

81

PDZ 2

Amino acid modifications

Modified residue

2

1

N-acetylserine Ref.5

Modified residue

46

1

Phosphoserine Ref.28

Modified residue

162

1

Phosphoserine Ref.30

Modified residue

269

1

Phosphoserine Ref.30

Modified residue

280

1

Phosphoserine Ref.20 Ref.21 Ref.22 Ref.24 Ref.28 Ref.30

Modified residue

288

1

Phosphoserine By similarity

Modified residue

290

1

Phosphoserine

Modified residue

291

1

Phosphoserine

Modified residue

293

1

Phosphothreonine

Modified residue

294

1

Phosphoserine By similarity

Modified residue

302

1

Phosphoserine By similarity

Natural variations

Natural variant

68

1

E → A in NPHLOP2; impairs the interaction with SLC34A1; causes a reduction of SLC34A1 amount on cell membrane and affects SLC34A1-dependent phosphate uptake. Ref.31

VAR_067661

Natural variant

110

1

L → 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.38
Corresponds to variant rs35910969 [ dbSNP | Ensembl ].

VAR_034899

Natural variant

153

1

R → Q in NPHLOP2; the mutant expressed in cultured renal cells increases the generation of cAMP by PTH and inhibits phosphate transport. Ref.38
Corresponds to variant rs41282065 [ dbSNP | Ensembl ].

VAR_048021

Natural variant

225

1

E → K in NPHLOP2; the mutant expressed in cultured renal cells increases the generation of cAMP by PTH and inhibits phosphate transport. Ref.38

VAR_048022

Experimental info

Mutagenesis

355

1

F → R: Loss of MSX binding. Ref.35

Mutagenesis

358

1

Missing: Reduces MSX binding. Ref.35

Secondary structure

1

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358

Helix Strand Turn

Details...

Beta strand

13 – 18

6

Beta strand

26 – 30

5

Beta strand

32 – 34

3

Beta strand

35 – 42

8

Helix

47 – 50

4

Beta strand

58 – 62

5

Helix

72 – 80

9

Beta strand

83 – 91

9

Beta strand

153 – 158

6

Turn

160 – 162

3

Beta strand

166 – 170

5

Beta strand

172 – 182

11

Helix

187 – 191

5

Beta strand

198 – 202

5

Helix

212 – 221

10

Turn

222 – 224

3

Beta strand

225 – 233

9

Helix

248 – 251

4

Beta strand

286 – 289

4

Helix

297 – 299

3

Beta strand

300 – 302

3

Beta strand

313 – 315

3

Helix

323 – 328

6

Helix

329 – 333

5

Helix

348 – 355

8

Sequences

	Sequence		Length	Mass (Da)
	O14745 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: E33AF87016D37A65	FASTA	358	38,868
	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

References

	« Hide 'large scale' referencesShow '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, 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]	"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.
[19]	"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.
[20]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[21]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[22]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[23]	"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.
[24]	"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, MASS SPECTROMETRY. Tissue: Platelet.
[25]	"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.
[26]	"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.
[27]	"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.
[28]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[29]	"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].
[30]	"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, MASS SPECTROMETRY.
[31]	"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.
[32]	"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.
[33]	"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.
[34]	"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.
[35]	"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.
[36]	"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.
[37]	"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.
[38]	"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.

IPI

IPI00003527.

RefSeq

NP_004243.1. NM_004252.4.

UniGene

Hs.741153.
Hs.741251.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1G9O	X-ray	1.50	A	11-99	[»]
1GQ4	X-ray	1.90	A	11-94	[»]
1GQ5	X-ray	2.20	A	11-94	[»]
1I92	X-ray	1.70	A	11-94	[»]
1SGH	X-ray	3.50	B	321-358	[»]
2D10	X-ray	2.50	E/F/G/H	331-358	[»]
2JXO	NMR	-	A	150-240	[»]
2KJD	NMR	-	A	150-270	[»]
2KRG	NMR	-	A	150-358	[»]
2OZF	X-ray	1.50	A	150-235	[»]

ProteinModelPortal

O14745.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29092N.

IntAct

O14745. 12 interactions.

MINT

MINT-4998796.

STRING

9606.ENSP00000262613.

Protein family/group databases

TCDB

8.A.24.1.1. ezrin/radixin/moesin-binding phosphoprotein 50 (EBP50) family.

PTM databases

PhosphoSite

O14745.

Proteomic databases

PaxDb

O14745.

PeptideAtlas

O14745.

PRIDE

O14745.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000262613; ENSP00000262613; ENSG00000109062.

GeneID

9368.

KEGG

hsa:9368.

UCSC

uc002jlo.3. human.

Organism-specific databases

CTD

9368.

GeneCards

GC17P072744.

HGNC

HGNC:11075. SLC9A3R1.

HPA

CAB001962.
HPA009672.
HPA027247.

MIM

604990. gene.
612287. phenotype.

neXtProt

NX_O14745.

Orphanet

244305. Dominant hypophosphatemia with nephrolithiasis or osteoporosis.

PharmGKB

PA35931.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG321335.

HOGENOM

HOG000089940.

HOVERGEN

HBG052616.

InParanoid

O14745.

KO

K13365.

OMA

VEKETHQ.

PhylomeDB

O14745.

Enzyme and pathway databases

Pathway_Interaction_DB

pdgfrbpathway. PDGFR-beta signaling pathway.
txa2pathway. Thromboxane A2 receptor signaling.

Gene expression databases

ArrayExpress

O14745.

Bgee

O14745.

CleanEx

HS_SLC9A3R1.

Genevestigator

O14745.

GermOnline

ENSG00000109062. Homo sapiens.

Family and domain databases

InterPro

IPR015098. EBP50_C-term.
IPR017300. NaH_exchngr_reg_CF_NHE-RF.
IPR001478. PDZ.
[Graphical view]

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

ChiTaRS

SLC9A3R1. human.

EvolutionaryTrace

O14745.

GenomeRNAi

9368.

NextBio

35084.

SOURCE

Search...

Entry information

Entry name

NHRF1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 139 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.