Biology:Sodium-hydrogen antiporter 3 regulator 1
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Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
Sodium-hydrogen antiporter 3 regulator 1 is a regulator of Sodium-hydrogen antiporter 3. It is encoded by the gene SLC9A3R1. It is also known as ERM Binding Protein 50 (EBP50) or Na+/H+ Exchanger Regulatory Factor (NHERF1). It is believed[1] to interact via long-range allostery, involving significant protein dynamics.
Mechanism
Members of the ezrin (VIL2; MIM 123900)-radixin (RDX; MIM 179410)-moesin (MSN; MIM 309845) (ERM) protein family are highly concentrated in the apical aspect of polarized epithelial cells. These cells are studded with microvilli containing bundles of actin filaments, which must attach to the membrane to assemble and maintain the microvilli. The ERM proteins, together with merlin, the NF2 (MIM 607379) gene product, are thought to be linkers between integral membrane and cytoskeletal proteins, and they bind directly to actin in vitro. Actin cytoskeleton reorganization requires the activation of a sodium/hydrogen exchanger (SLC9A3; MIM 182307). SLC9A3R1 is an ERM-binding protein.[supplied by OMIM][2]
Interactions
Sodium-hydrogen antiporter 3 regulator 1 has been shown to interact with:
- ADRB2,[3][4][5]
- Beta-catenin,[6]
- CFTR,[4][7][8][9][10][11][12]
- GNAQ,[13]
- OPRK1,[14][15]
- PAG1,[16]
- PDGFRA,[17]
- PDGFRB,[17]
- PDZK1,[18]
- PTH1R,[19]
- SLC4A8,[7][20]
- YAP1,[21] and
- EZR[16][22]
See also
- Cystic fibrosis transmembrane conductance regulator
- Ezrin
- Moesin
- Neutron spin echo
- Radixin
- Solute carrier family
References
- ↑ "Activation of nanoscale allosteric protein domain motion revealed by neutron spin echo spectroscopy". Biophys. J. 99 (10): 3473–82. November 2010. doi:10.1016/j.bpj.2010.09.058. PMID 21081097. Bibcode: 2010BpJ....99.3473F.
- ↑ "Entrez Gene: SLC9A3R1 solute carrier family 9 (sodium/hydrogen exchanger), member 3 regulator 1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9368.
- ↑ "Structural determinants of the Na+/H+ exchanger regulatory factor interaction with the beta 2 adrenergic and platelet-derived growth factor receptors". J. Biol. Chem. 277 (21): 18973–8. May 2002. doi:10.1074/jbc.M201507200. PMID 11882663.
- ↑ 4.0 4.1 "A C-terminal motif found in the beta2-adrenergic receptor, P2Y1 receptor and cystic fibrosis transmembrane conductance regulator determines binding to the Na+/H+ exchanger regulatory factor family of PDZ proteins". Proc. Natl. Acad. Sci. U.S.A. 95 (15): 8496–501. July 1998. doi:10.1073/pnas.95.15.8496. PMID 9671706. Bibcode: 1998PNAS...95.8496H.
- ↑ "The beta2-adrenergic receptor interacts with the Na+/H+-exchanger regulatory factor to control Na+/H+ exchange". Nature 392 (6676): 626–30. April 1998. doi:10.1038/33458. PMID 9560162. Bibcode: 1998Natur.392..626H.
- ↑ "EBP50, a beta-catenin-associating protein, enhances Wnt signaling and is over-expressed in hepatocellular carcinoma". Hepatology 38 (1): 178–86. July 2003. doi:10.1053/jhep.2003.50270. PMID 12830000.
- ↑ 7.0 7.1 "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. 277 (52): 50503–9. Dec 2002. doi:10.1074/jbc.M201862200. PMID 12403779.
- ↑ "C-terminal phosphorylation of MRP2 modulates its interaction with PDZ proteins". Biochem. Biophys. Res. Commun. 302 (3): 454–61. March 2003. doi:10.1016/S0006-291X(03)00196-7. PMID 12615054.
- ↑ "Peptide binding consensus of the NHE-RF-PDZ1 domain matches the C-terminal sequence of cystic fibrosis transmembrane conductance regulator (CFTR)". FEBS Lett. 427 (1): 103–8. May 1998. doi:10.1016/S0014-5793(98)00402-5. PMID 9613608.
- ↑ "The PDZ-interacting domain of cystic fibrosis transmembrane conductance regulator is required for functional expression in the apical plasma membrane". J. Biol. Chem. 275 (35): 27069–74. September 2000. doi:10.1074/jbc.M004951200. PMID 10852925.
- ↑ "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. 278 (8): 6440–9. February 2003. doi:10.1074/jbc.M211050200. PMID 12471024.
- ↑ "An apical PDZ protein anchors the cystic fibrosis transmembrane conductance regulator to the cytoskeleton". J. Biol. Chem. 273 (31): 19797–801. July 1998. doi:10.1074/jbc.273.31.19797. PMID 9677412.
- ↑ "Regulation of GTP-binding protein alpha q (Galpha q) signaling by the ezrin-radixin-moesin-binding phosphoprotein-50 (EBP50)". J. Biol. Chem. 277 (43): 40751–9. October 2002. doi:10.1074/jbc.M207910200. PMID 12193606.
- ↑ "kappa Opioid receptor interacts with Na(+)/H(+)-exchanger regulatory factor-1/Ezrin-radixin-moesin-binding phosphoprotein-50 (NHERF-1/EBP50) to stimulate Na(+)/H(+) exchange independent of G(i)/G(o) proteins". J. Biol. Chem. 279 (24): 25002–9. June 2004. doi:10.1074/jbc.M313366200. PMID 15070904.
- ↑ "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. 277 (30): 27545–52. July 2002. doi:10.1074/jbc.M200058200. PMID 12004055.
- ↑ 16.0 16.1 "Interaction between two adapter proteins, PAG and EBP50: a possible link between membrane rafts and actin cytoskeleton". FEBS Lett. 507 (2): 133–6. October 2001. doi:10.1016/S0014-5793(01)02955-6. PMID 11684085.
- ↑ 17.0 17.1 "Platelet-derived growth factor receptor association with Na(+)/H(+) exchanger regulatory factor potentiates receptor activity". Mol. Cell. Biol. 20 (22): 8352–63. November 2000. doi:10.1128/MCB.20.22.8352-8363.2000. PMID 11046132.
- ↑ "PDZK1: I. a major scaffolder in brush borders of proximal tubular cells". Kidney Int. 64 (5): 1733–45. November 2003. doi:10.1046/j.1523-1755.2003.00266.x. PMID 14531806.
- ↑ "Na(+)/H(+ ) exchanger regulatory factor 2 directs parathyroid hormone 1 receptor signalling". Nature 417 (6891): 858–61. June 2002. doi:10.1038/nature00816. PMID 12075354. Bibcode: 2002Natur.417..858M.
- ↑ "The COOH termini of NBC3 and the 56-kDa H+-ATPase subunit are PDZ motifs involved in their interaction". Am. J. Physiol., Cell Physiol. 284 (3): C667–73. March 2003. doi:10.1152/ajpcell.00225.2002. PMID 12444018.
- ↑ "Yes-associated protein 65 localizes p62(c-Yes) to the apical compartment of airway epithelia by association with EBP50". J. Cell Biol. 147 (4): 879–90. November 1999. doi:10.1083/jcb.147.4.879. PMID 10562288.
- ↑ "Identification of EBP50: A PDZ-containing phosphoprotein that associates with members of the ezrin-radixin-moesin family". J. Cell Biol. 139 (1): 169–79. October 1997. doi:10.1083/jcb.139.1.169. PMID 9314537.
Further reading
- "Characterization of a protein cofactor that mediates protein kinase A regulation of the renal brush border membrane Na(+)-H+ exchanger". J. Clin. Invest. 95 (5): 2143–9. 1995. doi:10.1172/JCI117903. PMID 7738182.
- "cAMP-mediated inhibition of the epithelial brush border Na+/H+ exchanger, NHE3, requires an associated regulatory protein". Proc. Natl. Acad. Sci. U.S.A. 94 (7): 3010–5. 1997. doi:10.1073/pnas.94.7.3010. PMID 9096337. Bibcode: 1997PNAS...94.3010Y.
- "NHE-RF, a regulatory cofactor for Na(+)-H+ exchange, is a common interactor for merlin and ERM (MERM) proteins". J. Biol. Chem. 273 (3): 1273–6. 1998. doi:10.1074/jbc.273.3.1273. PMID 9430655.
- "G protein-coupled receptor kinase 6A phosphorylates the Na(+)/H(+) exchanger regulatory factor via a PDZ domain-mediated interaction". J. Biol. Chem. 274 (34): 24328–34. 1999. doi:10.1074/jbc.274.34.24328. PMID 10446210.
- "A kinase-regulated PDZ-domain interaction controls endocytic sorting of the beta2-adrenergic receptor". Nature 401 (6750): 286–90. 1999. doi:10.1038/45816. PMID 10499588. Bibcode: 1999Natur.401..286C.
- "The B1 subunit of the H+ATPase is a PDZ domain-binding protein. Colocalization with NHE-RF in renal B-intercalated cells". J. Biol. Chem. 275 (24): 18219–24. 2000. doi:10.1074/jbc.M909857199. PMID 10748165.
- "Association of mammalian trp4 and phospholipase C isozymes with a PDZ domain-containing protein, NHERF". J. Biol. Chem. 275 (48): 37559–64. 2001. doi:10.1074/jbc.M006635200. PMID 10980202.
- "Interaction of the type IIa Na/Pi cotransporter with PDZ proteins". J. Biol. Chem. 276 (12): 9206–13. 2001. doi:10.1074/jbc.M008745200. PMID 11099500.
- "Identification of Epi64, a Tbc/Rabgap Domain–Containing Microvillar Protein That Binds to the First PDZ Domain of Ebp50 and E3karp". J. Cell Biol. 153 (1): 191–206. 2001. doi:10.1083/jcb.153.1.191. PMID 11285285.
- "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. 276 (23): 19683–6. 2001. doi:10.1074/jbc.C100154200. PMID 11304524.
- "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. 308 (5): 963–73. 2001. doi:10.1006/jmbi.2001.4634. PMID 11352585.
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