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8.A.24.1.1
NHERF1; NHERF-1; EBP50; SlcA3R1.  Na+/H+ exchanger regulatory factor (NHERF) proteins are a family of PSD-95/Discs-large/ZO-1 (PDZ)-scaffolding proteins, three of which (NHERFs 1-3) are localized to the brush border in kidney and intestinal epithelial cells. All NHERF proteins are involved in anchoring membrane proteins that contain PDZ recognition motifs to form multiprotein signaling complexes.  These NHERF proteins exhibit differential mobility in membranes (Yang et al. 2013).  Sites involved in binding to NPT2A (TC# 2.A.58.1.1) have been identified (Mamonova et al. 2015).

Accession Number:O14745
Protein Name:EBP50 aka NHERF-1
Length:358
Molecular Weight:38868.00
Species:Homo sapiens (Human) [9606]
Location1 / Topology2 / Orientation3: Endomembrane system1 / Peripheral membrane protein2
Substrate NONE

Cross database links:

Genevestigator: O14745 O14745
eggNOG: prNOG08540 NOG321335
HEGENOM: HBG714863 HOG000089940
DIP: DIP-29092N DIP-29092N
RefSeq: NP_004243.1   
Entrez Gene ID: 9368   
Pfam: PF09007    PF00595   
OMIM: 604990  gene
612287  phenotype
KEGG: hsa:9368    hsa:9368   

Gene Ontology

GO:0015629 C:actin cytoskeleton
GO:0012505 C:endomembrane system
GO:0030175 C:filopodium
GO:0043231 C:intracellular membrane-bounded organelle
GO:0005902 C:microvillus
GO:0001726 C:ruffle
GO:0031698 F:beta-2 adrenergic receptor binding
GO:0030165 F:PDZ domain binding
GO:0006461 P:protein complex assembly
GO:0032415 P:regulation of sodium:hydrogen antiporter ac...
GO:0016055 P:Wnt receptor signaling pathway
GO:0016324 C:apical plasma membrane
GO:0031526 C:brush border membrane
GO:0005813 C:centrosome
GO:0031528 C:microvillus membrane
GO:0017081 F:chloride channel regulator activity
GO:0030036 P:actin cytoskeleton organization
GO:0007191 P:adenylate cyclase-activating dopamine receptor signaling pathway
GO:0060158 P:phospholipase C-activating dopamine receptor signaling pathway
GO:0006915 P:apoptotic process
GO:0032782 P:bile acid secretion
GO:0030643 P:cellular phosphate ion homeostasis
GO:0034613 P:cellular protein localization
GO:0034635 P:glutathione transport
GO:0030033 P:microvillus assembly
GO:0030336 P:negative regulation of cell migration
GO:0008285 P:negative regulation of cell proliferation
GO:0070373 P:negative regulation of ERK1 and ERK2 cascade
GO:0014067 P:negative regulation of phosphatidylinositol 3-kinase cascade
GO:0010642 P:negative regulation of platelet-derived growth factor receptor signaling pathway
GO:0051898 P:negative regulation of protein kinase B signaling cascade
GO:0010766 P:negative regulation of sodium ion transport
GO:0032416 P:negative regulation of sodium:hydrogen antiporter activity
GO:0044062 P:regulation of excretion
GO:0045859 P:regulation of protein kinase activity
GO:0032415 P:regulation of sodium:hydrogen antiporter activity
GO:0097291 P:renal phosphate ion absorption
GO:0003096 P:renal sodium ion transport

References (62)

[1] “Identification of EBP50: a PDZ-containing phosphoprotein that associates with members of the ezrin-radixin-moesin family.”  Reczek D.et.al.   9314537
[2] “NHE-RF, a regulatory cofactor for Na(+)-H+ exchange, is a common interactor for merlin and ERM (MERM) proteins.”  Murthy A.et.al.   9430655
[3] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[4] “Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides.”  Gevaert K.et.al.   12665801
[5] “cAMP-mediated inhibition of the epithelial brush border Na+/H+ exchanger, NHE3, requires an associated regulatory protein.”  Yun C.H.C.et.al.   9096337
[6] “A kinase-regulated PDZ-domain interaction controls endocytic sorting of the beta2-adrenergic receptor.”  Cao T.T.et.al.   10499588
[7] “Interaction between two adapter proteins, PAG and EBP50: a possible link between membrane rafts and actin cytoskeleton.”  Brdickova N.et.al.   11684085
[8] “Identification of EPI64, a TBC/rabGAP domain-containing microvillar protein that binds to the first PDZ domain of EBP50 and E3KARP.”  Reczek D.et.al.   11285285
[9] “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.et.al.   11956211
[10] “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.et.al.   12004055
[11] “Epithelial inducible nitric-oxide synthase is an apical EBP50-binding protein that directs vectorial nitric oxide output.”  Glynne P.A.et.al.   12080081
[12] “Regulation of GTP-binding protein alpha q (Galpha q) signaling by the ezrin-radixin-moesin-binding phosphoprotein-50 (EBP50).”  Rochdi M.D.et.al.   12193606
[13] “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.et.al.   12403779
[14] “The PDZ-interacting domain of TRPC4 controls its localization and surface expression in HEK293 cells.”  Mery L.et.al.   12154080
[15] “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.et.al.   12145337
[16] “The COOH termini of NBC3 and the 56-kDa H+-ATPase subunit are PDZ motifs involved in their interaction.”  Pushkin A.et.al.   12444018
[17] “EBP50, a beta-catenin-associating protein, enhances Wnt signaling and is over-expressed in hepatocellular carcinoma.”  Shibata T.et.al.   12830000
[18] “The PDZ-binding chloride channel ClC-3B localizes to the Golgi and associates with cystic fibrosis transmembrane conductance regulator-interacting PDZ proteins.”  Gentzsch M.et.al.   12471024
[19] “Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.”  Olsen J.V.et.al.   17081983
[20] “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.et.al.   17924679
[21] “Phosphoproteome of resting human platelets.”  Zahedi R.P.et.al.   18088087
[22] “Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis.”  Cantin G.T.et.al.   18220336
[23] “A quantitative atlas of mitotic phosphorylation.”  Dephoure N.et.al.   18669648
[24] “MCC, a new interacting protein for Scrib, is required for cell migration in epithelial cells.”  Arnaud C.et.al.   19555689
[25] “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.et.al.   11304524
[26] “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.et.al.   11352585
[27] “Structural determinants of the Na+/H+ exchanger regulatory factor interaction with the beta 2 adrenergic and platelet-derived growth factor receptors.”  Karthikeyan S.et.al.   11882663
[28] “The EBP50-moesin interaction involves a binding site regulated by direct masking on the FERM domain.”  Finnerty C.M.et.al.   15020681
[29] “Structural basis for NHERF recognition by ERM proteins.”  Terawaki S.et.al.   16615918
[30] “NHERF1 mutations and responsiveness of renal parathyroid hormone.”  Karim Z.et.al.   18784102
[31] “Identification of EBP50: a PDZ-containing phosphoprotein that associates with members of the ezrin-radixin-moesin family.”  Reczek D.et.al.   9314537
[32] “NHE-RF, a regulatory cofactor for Na(+)-H+ exchange, is a common interactor for merlin and ERM (MERM) proteins.”  Murthy A.et.al.   9430655
[33] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[34] “Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides.”  Gevaert K.et.al.   12665801
[35] “cAMP-mediated inhibition of the epithelial brush border Na+/H+ exchanger, NHE3, requires an associated regulatory protein.”  Yun C.H.C.et.al.   9096337
[36] “A kinase-regulated PDZ-domain interaction controls endocytic sorting of the beta2-adrenergic receptor.”  Cao T.T.et.al.   10499588
[37] “Interaction between two adapter proteins, PAG and EBP50: a possible link between membrane rafts and actin cytoskeleton.”  Brdickova N.et.al.   11684085
[38] “Identification of EPI64, a TBC/rabGAP domain-containing microvillar protein that binds to the first PDZ domain of EBP50 and E3KARP.”  Reczek D.et.al.   11285285
[39] “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.et.al.   11956211
[40] “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.et.al.   12004055
[41] “Epithelial inducible nitric-oxide synthase is an apical EBP50-binding protein that directs vectorial nitric oxide output.”  Glynne P.A.et.al.   12080081
[42] “Regulation of GTP-binding protein alpha q (Galpha q) signaling by the ezrin-radixin-moesin-binding phosphoprotein-50 (EBP50).”  Rochdi M.D.et.al.   12193606
[43] “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.et.al.   12403779
[44] “The PDZ-interacting domain of TRPC4 controls its localization and surface expression in HEK293 cells.”  Mery L.et.al.   12154080
[45] “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.et.al.   12145337
[46] “The COOH termini of NBC3 and the 56-kDa H+-ATPase subunit are PDZ motifs involved in their interaction.”  Pushkin A.et.al.   12444018
[47] “EBP50, a beta-catenin-associating protein, enhances Wnt signaling and is over-expressed in hepatocellular carcinoma.”  Shibata T.et.al.   12830000
[48] “The PDZ-binding chloride channel ClC-3B localizes to the Golgi and associates with cystic fibrosis transmembrane conductance regulator-interacting PDZ proteins.”  Gentzsch M.et.al.   12471024
[49] “Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.”  Olsen J.V.et.al.   17081983
[50] “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.et.al.   17924679
[51] “Phosphoproteome of resting human platelets.”  Zahedi R.P.et.al.   18088087
[52] “Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis.”  Cantin G.T.et.al.   18220336
[53] “A quantitative atlas of mitotic phosphorylation.”  Dephoure N.et.al.   18669648
[54] “MCC, a new interacting protein for Scrib, is required for cell migration in epithelial cells.”  Arnaud C.et.al.   19555689
[55] “Initial characterization of the human central proteome.”  Burkard T.R.et.al.   21269460
[56] “A new human NHERF1 mutation decreases renal phosphate transporter NPT2a expression by a PTH-independent mechanism.”  Courbebaisse M.et.al.   22506049
[57] “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.et.al.   11304524
[58] “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.et.al.   11352585
[59] “Structural determinants of the Na+/H+ exchanger regulatory factor interaction with the beta 2 adrenergic and platelet-derived growth factor receptors.”  Karthikeyan S.et.al.   11882663
[60] “The EBP50-moesin interaction involves a binding site regulated by direct masking on the FERM domain.”  Finnerty C.M.et.al.   15020681
[61] “Structural basis for NHERF recognition by ERM proteins.”  Terawaki S.et.al.   16615918
[62] “NHERF1 mutations and responsiveness of renal parathyroid hormone.”  Karim Z.et.al.   18784102
Structure:
1G9O   1GQ4   1GQ5   1I92   1SGH   2D10   2JXO   2KJD   2KRG   2OZF   [...more]

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FASTA formatted sequence
1:	MSADAAAGAP LPRLCCLEKG PNGYGFHLHG EKGKLGQYIR LVEPGSPAEK AGLLAGDRLV 
61:	EVNGENVEKE THQQVVSRIR AALNAVRLLV VDPETDEQLQ KLGVQVREEL LRAQEAPGQA 
121:	EPPAAAEVQG AGNENEPREA DKSHPEQREL RPRLCTMKKG PSGYGFNLHS DKSKPGQFIR 
181:	SVDPDSPAEA SGLRAQDRIV EVNGVCMEGK QHGDVVSAIR AGGDETKLLV VDRETDEFFK 
241:	KCRVIPSQEH LNGPLPVPFT NGEIQKENSR EALAEAALES PRPALVRSAS SDTSEELNSQ 
301:	DSPPKQDSTA PSSTSSSDPI LDFNISLAMA KERAHQKRSS KRAPQMDWSK KNELFSNL