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Showing Protein Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (HMDBP01793)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 1 metabolite
Identification
HMDB Protein ID HMDBP01793
Secondary Accession Numbers
  • 7150
Name Na(+)/H(+) exchange regulatory cofactor NHE-RF1
Synonyms
  1. EBP50
  2. Ezrin-radixin-moesin-binding phosphoprotein 50
  3. NHERF-1
  4. Regulatory cofactor of Na(+)/H(+) exchanger
  5. Sodium-hydrogen exchanger regulatory factor 1
  6. Solute carrier family 9 isoform A3 regulatory factor 1
Gene Name SLC9A3R1
Protein Type Unknown
Biological Properties
General Function Posttranslational modification, protein turnover, chaperones
Specific 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. Interacts with MCC
Pathways Not Available
Reactions Not Available
GO Classification
Function
binding
protein binding
Cellular Location
  1. Cytoplasm
  2. Endomembrane system
  3. Peripheral membrane protein
  4. Apical cell membrane
  5. Cell projection
  6. Cell projection
  7. Cell projection
  8. filopodium
  9. ruffle
  10. microvillus
Gene Properties
Chromosome Location Chromosome:1
Locus 17q25.1
SNPs SLC9A3R1
Gene Sequence 
>1077 bp
ATGAGCGCGGACGCAGCGGCCGGGGCGCCCCTGCCCCGGCTCTGCTGCCTGGAGAAGGGT
CCGAACGGCTACGGCTTCCACCTGCACGGGGAGAAGGGCAAGTTGGGCCAGTACATCCGG
CTGGTGGAGCCCGGCTCGCCGGCCGAGAAGGCGGGGCTGCTGGCGGGGGACCGGCTGGTG
GAGGTGAACGGCGAAAACGTGGAGAAGGAGACCCACCAGCAGGTGGTGAGCCGCATCCGC
GCCGCACTCAACGCCGTGCGCCTGCTGGTGGTCGACCCCGAGACGGACGAGCAGCTGCAG
AAGCTCGGCGTCCAGGTCCGAGAGGAGCTGCTGCGCGCCCAGGAAGCGCCGGGGCAGGCC
GAGCCGCCGGCCGCCGCCGAGGTGCAGGGGGCTGGCAACGAAAATGAGCCTCGCGAGGCC
GACAAGAGCCACCCGGAGCAGCGCGAGCTTCGGCCTCGGCTCTGTACCATGAAGAAGGGC
CCCAGTGGCTATGGCTTCAACCTGCACAGCGACAAGTCCAAGCCAGGCCAGTTCATCCGG
TCAGTGGACCCAGACTCCCCGGCTGAGGCTTCAGGGCTCCGGGCCCAGGATCGCATTGTG
GAGGTGAACGGGGTCTGCATGGAGGGGAAGCAGCATGGGGACGTGGTGTCCGCCATCAGG
GCTGGCGGGGACGAGACCAAGCTGCTGGTGGTGGACAGGGAAACTGACGAGTTCTTCAAG
AAATGCAGAGTGATCCCATCTCAGGAGCACCTGAATGGTCCCCTGCCTGTGCCCTTCACC
AATGGGGAGATACAGAAGGAGAACAGTCGTGAAGCCCTGGCAGAGGCAGCCTTGGAGAGC
CCCAGGCCAGCCCTGGTGAGATCCGCCTCCAGTGACACCAGCGAGGAGCTGAATTCCCAA
GACAGCCCCCCAAAACAGGACTCCACAGCGCCCTCGTCTACCTCCTCCTCCGACCCCATC
CTAGACTTCAACATCTCCCTGGCCATGGCCAAAGAGAGGGCCCACCAGAAACGCAGCAGC
AAACGGGCCCCGCAGATGGACTGGAGCAAGAAAAACGAACTCTTCAGCAACCTCTGA
Protein Properties
Number of Residues 358
Molecular Weight 38868.1
Theoretical pI 5.52
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence 
>Na(+)/H(+) exchange regulatory cofactor NHE-RF1
MSADAAAGAPLPRLCCLEKGPNGYGFHLHGEKGKLGQYIRLVEPGSPAEKAGLLAGDRLV
EVNGENVEKETHQQVVSRIRAALNAVRLLVVDPETDEQLQKLGVQVREELLRAQEAPGQA
EPPAAAEVQGAGNENEPREADKSHPEQRELRPRLCTMKKGPSGYGFNLHSDKSKPGQFIR
SVDPDSPAEASGLRAQDRIVEVNGVCMEGKQHGDVVSAIRAGGDETKLLVVDRETDEFFK
KCRVIPSQEHLNGPLPVPFTNGEIQKENSREALAEAALESPRPALVRSASSDTSEELNSQ
DSPPKQDSTAPSSTSSSDPILDFNISLAMAKERAHQKRSSKRAPQMDWSKKNELFSNL
GenBank ID Protein 3220019
UniProtKB/Swiss-Prot ID O14745
UniProtKB/Swiss-Prot Entry Name NHRF1_HUMAN
PDB IDs
GenBank Gene ID AF015926
GeneCard ID SLC9A3R1
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  3. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [PubMed:17081983 ]
  4. Yu LR, Zhu Z, Chan KC, Issaq HJ, Dimitrov DS, Veenstra TD: 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. J Proteome Res. 2007 Nov;6(11):4150-62. Epub 2007 Oct 9. [PubMed:17924679 ]
  5. Zahedi RP, Lewandrowski U, Wiesner J, Wortelkamp S, Moebius J, Schutz C, Walter U, Gambaryan S, Sickmann A: Phosphoproteome of resting human platelets. J Proteome Res. 2008 Feb;7(2):526-34. Epub 2007 Dec 19. [PubMed:18088087 ]
  6. Cantin GT, Yi W, Lu B, Park SK, Xu T, Lee JD, Yates JR 3rd: Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J Proteome Res. 2008 Mar;7(3):1346-51. doi: 10.1021/pr0705441. Epub 2008 Jan 26. [PubMed:18220336 ]
  7. Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J: Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol. 2003 May;21(5):566-9. Epub 2003 Mar 31. [PubMed:12665801 ]
  8. Glynne PA, Darling KE, Picot J, Evans TJ: Epithelial inducible nitric-oxide synthase is an apical EBP50-binding protein that directs vectorial nitric oxide output. J Biol Chem. 2002 Sep 6;277(36):33132-8. Epub 2002 Jun 21. [PubMed:12080081 ]
  9. Pushkin A, Abuladze N, Newman D, Muronets V, Sassani P, Tatishchev S, Kurtz I: The COOH termini of NBC3 and the 56-kDa H+-ATPase subunit are PDZ motifs involved in their interaction. Am J Physiol Cell Physiol. 2003 Mar;284(3):C667-73. Epub 2002 Nov 20. [PubMed:12444018 ]
  10. Karthikeyan S, Leung T, Ladias JA: Structural determinants of the Na+/H+ exchanger regulatory factor interaction with the beta 2 adrenergic and platelet-derived growth factor receptors. J Biol Chem. 2002 May 24;277(21):18973-8. Epub 2002 Mar 6. [PubMed:11882663 ]
  11. Cao TT, Deacon HW, Reczek D, Bretscher A, von Zastrow M: A kinase-regulated PDZ-domain interaction controls endocytic sorting of the beta2-adrenergic receptor. Nature. 1999 Sep 16;401(6750):286-90. [PubMed:10499588 ]
  12. Reczek D, Berryman M, Bretscher A: Identification of EBP50: A PDZ-containing phosphoprotein that associates with members of the ezrin-radixin-moesin family. J Cell Biol. 1997 Oct 6;139(1):169-79. [PubMed:9314537 ]
  13. Murthy A, Gonzalez-Agosti C, Cordero E, Pinney D, Candia C, Solomon F, Gusella J, Ramesh V: NHE-RF, a regulatory cofactor for Na(+)-H+ exchange, is a common interactor for merlin and ERM (MERM) proteins. J Biol Chem. 1998 Jan 16;273(3):1273-6. [PubMed:9430655 ]
  14. Yun CH, Oh S, Zizak M, Steplock D, Tsao S, Tse CM, Weinman EJ, Donowitz M: cAMP-mediated inhibition of the epithelial brush border Na+/H+ exchanger, NHE3, requires an associated regulatory protein. Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3010-5. [PubMed:9096337 ]
  15. Brdickova N, Brdicka T, Andera L, Spicka J, Angelisova P, Milgram SL, Horejsi V: Interaction between two adapter proteins, PAG and EBP50: a possible link between membrane rafts and actin cytoskeleton. FEBS Lett. 2001 Oct 26;507(2):133-6. [PubMed:11684085 ]
  16. Reczek D, Bretscher A: Identification of EPI64, a TBC/rabGAP domain-containing microvillar protein that binds to the first PDZ domain of EBP50 and E3KARP. J Cell Biol. 2001 Apr 2;153(1):191-206. [PubMed:11285285 ]
  17. Liedtke CM, Yun CH, Kyle N, Wang D: 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. J Biol Chem. 2002 Jun 21;277(25):22925-33. Epub 2002 Apr 15. [PubMed:11956211 ]
  18. Li JG, Chen C, Liu-Chen LY: 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. J Biol Chem. 2002 Jul 26;277(30):27545-52. Epub 2002 May 9. [PubMed:12004055 ]
  19. Rochdi MD, Watier V, La Madeleine C, Nakata H, Kozasa T, Parent JL: Regulation of GTP-binding protein alpha q (Galpha q) signaling by the ezrin-radixin-moesin-binding phosphoprotein-50 (EBP50). J Biol Chem. 2002 Oct 25;277(43):40751-9. Epub 2002 Aug 21. [PubMed:12193606 ]
  20. Park M, Ko SB, Choi JY, Muallem G, Thomas PJ, Pushkin A, Lee MS, Kim JY, Lee MG, Muallem S, Kurtz I: The cystic fibrosis transmembrane conductance regulator interacts with and regulates the activity of the HCO3- salvage transporter human Na+-HCO3- cotransport isoform 3. J Biol Chem. 2002 Dec 27;277(52):50503-9. Epub 2002 Oct 25. [PubMed:12403779 ]
  21. Mery L, Strauss B, Dufour JF, Krause KH, Hoth M: The PDZ-interacting domain of TRPC4 controls its localization and surface expression in HEK293 cells. J Cell Sci. 2002 Sep 1;115(Pt 17):3497-508. [PubMed:12154080 ]
  22. Ediger TR, Park SE, Katzenellenbogen BS: 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. Mol Endocrinol. 2002 Aug;16(8):1828-39. [PubMed:12145337 ]
  23. Shibata T, Chuma M, Kokubu A, Sakamoto M, Hirohashi S: EBP50, a beta-catenin-associating protein, enhances Wnt signaling and is over-expressed in hepatocellular carcinoma. Hepatology. 2003 Jul;38(1):178-86. [PubMed:12830000 ]
  24. Gentzsch M, Cui L, Mengos A, Chang XB, Chen JH, Riordan JR: The PDZ-binding chloride channel ClC-3B localizes to the Golgi and associates with cystic fibrosis transmembrane conductance regulator-interacting PDZ proteins. J Biol Chem. 2003 Feb 21;278(8):6440-9. Epub 2002 Dec 5. [PubMed:12471024 ]
  25. Arnaud C, Sebbagh M, Nola S, Audebert S, Bidaut G, Hermant A, Gayet O, Dusetti NJ, Ollendorff V, Santoni MJ, Borg JP, Lecine P: MCC, a new interacting protein for Scrib, is required for cell migration in epithelial cells. FEBS Lett. 2009 Jul 21;583(14):2326-32. doi: 10.1016/j.febslet.2009.06.034. Epub 2009 Jun 24. [PubMed:19555689 ]
  26. Karthikeyan S, Leung T, Ladias JA: Structural basis of the Na+/H+ exchanger regulatory factor PDZ1 interaction with the carboxyl-terminal region of the cystic fibrosis transmembrane conductance regulator. J Biol Chem. 2001 Jun 8;276(23):19683-6. Epub 2001 Apr 13. [PubMed:11304524 ]
  27. Karthikeyan S, Leung T, Birrane G, Webster G, Ladias JA: 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. J Mol Biol. 2001 May 18;308(5):963-73. [PubMed:11352585 ]
  28. Finnerty CM, Chambers D, Ingraffea J, Faber HR, Karplus PA, Bretscher A: The EBP50-moesin interaction involves a binding site regulated by direct masking on the FERM domain. J Cell Sci. 2004 Mar 15;117(Pt 8):1547-52. [PubMed:15020681 ]
  29. Terawaki S, Maesaki R, Hakoshima T: Structural basis for NHERF recognition by ERM proteins. Structure. 2006 Apr;14(4):777-89. [PubMed:16615918 ]
  30. 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: NHERF1 mutations and responsiveness of renal parathyroid hormone. N Engl J Med. 2008 Sep 11;359(11):1128-35. doi: 10.1056/NEJMoa0802836. [PubMed:18784102 ]