Sodium-hydrogen exchange regulatory cofactor 2: Difference between revisions

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{{Infobox_gene}}
{{PBB_Controls
'''Sodium-hydrogen exchange regulatory cofactor NHE-RF2''' (NHERF-2) also known as '''tyrosine kinase activator protein 1''' (TKA-1) or '''SRY-interacting protein 1''' (SIP-1) is a [[protein]] that in humans is encoded by the ''SLC9A3R2'' (solute carrier family 9 isoform A3 regulatory factor 2) [[gene]].<ref name="pmid9054412">{{cite journal |vauthors=Poulat F, de Santa Barbara P, Desclozeaux M, Soullier S, Moniot B, Bonneaud N, Boizet B, Berta P | title = The human testis determining factor SRY binds a nuclear factor containing PDZ protein interaction domains | journal = J. Biol. Chem. | volume = 272 | issue = 11 | pages = 7167–72 |date=March 1997 | pmid = 9054412 | doi = 10.1074/jbc.272.11.7167 }}</ref><ref name="pmid9671706">{{cite journal |vauthors=Hall RA, Ostedgaard LS, Premont RT, Blitzer JT, Rahman N, Welsh MJ, Lefkowitz RJ | title = 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 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 95 | issue = 15 | pages = 8496–501 |date=July 1998 | pmid = 9671706 | pmc = 21104 | doi = 10.1073/pnas.95.15.8496}}</ref>
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
NHERF-2) is a scaffold protein that connects plasma membrane proteins with members of the [[Merlin (protein)|ezrin/moesin/radixin]] family and thereby helps to link them to the [[actin]] [[cytoskeleton]] and to regulate their surface expression. It is necessary for cAMP-mediated [[phosphorylation]] and inhibition of [[SLC9A3]]. In addition, it may also act as scaffold protein in the [[Cell nucleus|nucleus]].
{{GNF_Protein_box
| image = PBB_Protein_SLC9A3R2_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 2he4.
| PDB = {{PDB2|2he4}}, {{PDB2|2ocs}}
| Name = Solute carrier family 9 (sodium/hydrogen exchanger), member 3 regulator 2
| HGNCid = 11076
| Symbol = SLC9A3R2
| AltSymbols =; SIP1; E3KARP; MGC104639; NHE3RF2; NHERF-2; NHERF2; OCTS2; SIP-1; TKA-1
| OMIM = 606553
| ECnumber = 
| Homologene = 56962
| MGIid = 1890662
| GeneAtlas_image1 = PBB_GE_SLC9A3R2_209830_s_at_tn.png
| Function = {{GNF_GO|id=GO:0008022 |text = protein C-terminus binding}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005886 |text = plasma membrane}} {{GNF_GO|id=GO:0016324 |text = apical plasma membrane}}
| Process = {{GNF_GO|id=GO:0006461 |text = protein complex assembly}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 9351
    | Hs_Ensembl = ENSG00000065054
    | Hs_RefseqProtein = NP_004776
    | Hs_RefseqmRNA = NM_004785
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 16
    | Hs_GenLoc_start = 2016897
    | Hs_GenLoc_end = 2028481
    | Hs_Uniprot = Q15599
    | Mm_EntrezGene = 65962
    | Mm_Ensembl = ENSMUSG00000002504
    | Mm_RefseqmRNA = NM_023055
    | Mm_RefseqProtein = NP_075542
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 17
    | Mm_GenLoc_start = 24366888
    | Mm_GenLoc_end = 24377905
    | Mm_Uniprot = Q9JHL1
  }}
}}


== Function ==


This regulatory protein (factor) interacts with a sodium/hydrogen exchanger NHE3 ([[SLC9A3]]) in the brush border membrane of the [[proximal tubule]], [[small intestine]], and [[Colon (anatomy)|colon]] that plays a major role in transepithelial sodium absorption. SLC9A3R2, as well as [[SLC9A3R1]] and [[protein kinase A]] phosphorylation, may play a role in NHE3 regulation.<ref>{{cite web | title = Entrez Gene: SLC9A3R2 solute carrier family 9 (sodium/hydrogen exchanger), member 3 regulator 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9351| accessdate = }}</ref>


'''Sodium-hydrogen exchange regulatory cofactor 2''' (gene name '''SLC9A3R2'''; also known as '''NHERF-2''' and '''Tyrosine kinase activator protein 1''') is a human scaffold protein that connects plasma membrane proteins with members of the [[Merlin (protein)|ezrin/moesin/radixin]] family and thereby helps to link them to the [[actin]] [[cytoskeleton]] and to regulate their surface expression. It is necessary for cAMP-mediated [[phosphorylation]] and inhibition of [[SLC9A3]]. May also act as scaffold protein in the [[nucleus]].
==Interactions==
 
Sodium-hydrogen exchange regulatory cofactor 2 has been shown to [[Protein-protein interaction|interact]] with [[SGK]],<ref name=pmid12387817>{{cite journal |last=Chun |first=Jaesun |authorlink= |author2=Kwon Taegun |author3=Lee Eunjung |author4=Suh Pann-Ghill |author5=Choi Eui-Ju |author6=Sun Kang Sang |date=October 2002 |title=The Na(+)/H(+) exchanger regulatory factor 2 mediates phosphorylation of serum- and glucocorticoid-induced protein kinase 1 by 3-phosphoinositide-dependent protein kinase 1 |journal=Biochem. Biophys. Res. Commun. |volume=298 |issue=2 |pages=207–15 |publisher= |location = United States| issn = 0006-291X| pmid = 12387817 |doi=10.1016/S0006-291X(02)02428-2 }}</ref><ref name=pmid11751930>{{cite journal |last=Yun |first=C Chris |authorlink= |author2=Chen Yueping |author3=Lang Florian  |date=March 2002 |title=Glucocorticoid activation of Na(+)/H(+) exchanger isoform 3 revisited. The roles of SGK1 and NHERF2 |journal=J. Biol. Chem. |volume=277 |issue=10 |pages=7676–83 |publisher= |location = United States| issn = 0021-9258| pmid = 11751930 |doi = 10.1074/jbc.M107768200 }}</ref> [[Actinin alpha 4]],<ref name=pmid11948184>{{cite journal |vauthors = Kim JH, Lee-Kwon W, Park JB, Ryu SH, Yun CH, Donowitz M |date=June 2002 |title=Ca(2+)-dependent inhibition of Na+/H+ exchanger 3 (NHE3) requires an NHE3-E3KARP-alpha-actinin-4 complex for oligomerization and endocytosis |journal=J. Biol. Chem. |volume=277 |issue=26 |pages=23714–24 |publisher= |location = United States| issn = 0021-9258| pmid = 11948184 |doi = 10.1074/jbc.M200835200 }}</ref> [[Parathyroid hormone receptor 1]],<ref name=pmid12075354>{{cite journal |last=Mahon |first=Matthew J |authorlink= |author2=Donowitz Mark |author3=Yun C Chris |author4=Segre Gino V  |date=June 2002 |title=Na(+)/H(+ ) exchanger regulatory factor 2 directs parathyroid hormone 1 receptor signalling |journal=[[Nature (journal)|Nature]] |volume=417 |issue=6891 |pages=858–61 |publisher= |location = England| issn = 0028-0836| pmid = 12075354 |doi = 10.1038/nature00816 }}</ref> [[Phosphoinositide-dependent kinase-1]],<ref name=pmid12387817/> [[ezrin|EZR]],<ref name=pmid9748260>{{cite journal |last=Yun |first=C H |authorlink= |author2=Lamprecht G |author3=Forster D V |author4=Sidor A  |date=October 1998 |title=NHE3 kinase A regulatory protein E3KARP binds the epithelial brush border Na+/H+ exchanger NHE3 and the cytoskeletal protein ezrin |journal=J. Biol. Chem. |volume=273 |issue=40 |pages=25856–63 |publisher= |location = UNITED STATES| issn = 0021-9258| pmid = 9748260 |doi=10.1074/jbc.273.40.25856 }}</ref><ref name=pmid12080047>{{cite journal |last=Sitaraman |first=Shanthi V |authorlink= |author2=Wang Lixin |author3=Wong Michelle |author4=Bruewer Matthias |author5=Hobert Michael |author6=Yun C-H |author7=Merlin Didier |author8=Madara James L  |date=September 2002 |title=The adenosine 2b receptor is recruited to the plasma membrane and associates with E3KARP and Ezrin upon agonist stimulation |journal=J. Biol. Chem. |volume=277 |issue=36 |pages=33188–95 |publisher= |location = United States| issn = 0021-9258| pmid = 12080047 |doi = 10.1074/jbc.M202522200 }}</ref> [[PODXL]],<ref name=pmid15642748>{{cite journal |last=Meder |first=Doris |authorlink= |author2=Shevchenko Anna |author3=Simons Kai |author4=Füllekrug Joachim  |date=January 2005 |title=Gp135/podocalyxin and NHERF-2 participate in the formation of a preapical domain during polarization of MDCK cells |journal=J. Cell Biol. |volume=168 |issue=2 |pages=303–13 |publisher= |location = United States| issn = 0021-9525| pmid = 15642748 |doi = 10.1083/jcb.200407072 |pmc=2171597 }}</ref><ref name=pmid11457882>{{cite journal |last=Takeda |first=T |authorlink= |author2=McQuistan T |author3=Orlando R A |author4=Farquhar M G  |date=July 2001 |title=Loss of glomerular foot processes is associated with uncoupling of podocalyxin from the actin cytoskeleton |journal=J. Clin. Invest. |volume=108 |issue=2 |pages=289–301 |publisher= |location = United States| issn = 0021-9738| pmid = 11457882 |doi = 10.1172/JCI12539 |pmc=203027 }}</ref><ref name=pmid11997330>{{cite journal |last=Li |first=Yong |authorlink= |author2=Li Jian |author3=Straight Samuel W |author4=Kershaw David B  |date=June 2002 |title=PDZ domain-mediated interaction of rabbit podocalyxin and Na(+)/H(+) exchange regulatory factor-2 |journal=Am. J. Physiol. Renal Physiol. |volume=282 |issue=6 |pages=F1129–39 |publisher= |location = United States| issn = 0363-6127| pmid = 11997330 |doi = 10.1152/ajprenal.00131.2001 }}</ref> [[Cystic fibrosis transmembrane conductance regulator]]<ref name=pmid10893422>{{cite journal |last=Sun |first=F |authorlink= |author2=Hug M J |author3=Lewarchik C M |author4=Yun C H |author5=Bradbury N A |author6=Frizzell R A  |date=September 2000 |title=E3KARP mediates the association of ezrin and protein kinase A with the cystic fibrosis transmembrane conductance regulator in airway cells |journal=J. Biol. Chem. |volume=275 |issue=38 |pages=29539–46 |publisher= |location = UNITED STATES| issn = 0021-9258| pmid = 10893422 |doi = 10.1074/jbc.M004961200 }}</ref> and [[PLCB3]].<ref name=pmid10748023>{{cite journal |last=Hwang |first=J I |authorlink= |author2=Heo K |author3=Shin K J |author4=Kim E |author5=Yun C |author6=Ryu S H |author7=Shin H S |author8=Suh P G  |date=June 2000 |title=Regulation of phospholipase C-beta 3 activity by Na+/H+ exchanger regulatory factor 2 |journal=J. Biol. Chem. |volume=275 |issue=22 |pages=16632–7 |publisher= |location = UNITED STATES| issn = 0021-9258| pmid = 10748023 |doi = 10.1074/jbc.M001410200 }}</ref>
<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
{{PBB_Summary
| section_title =  
| summary_text = This regulatory protein (factor) interacts with a sodium/hydrogen exchanger NHE3 ([[SLC9A3]]; MIM 182307) in the brush border membrane of the [[proximal tubule]], [[small intestine]], and [[colon]] that plays a major role in transepithelial sodium absorption. SLC9A3R2, as well as SLC9A3R1 (MIM 604990) and [[protein kinase A]] phosphorylation, may play a role in NHE3 regulation.[supplied by OMIM]<ref>{{cite web | title = Entrez Gene: SLC9A3R2 solute carrier family 9 (sodium/hydrogen exchanger), member 3 regulator 2| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9351| accessdate = }}</ref>
}}


==See also==
==See also==
Line 61: Line 15:


==References==
==References==
{{reflist|2}}
{{Reflist}}


==Further reading==
==Further reading==
{{refbegin | 2}}
{{Refbegin | 2}}
{{PBB_Further_reading
*{{cite journal   |vauthors=Yun CH, Oh S, Zizak M, etal |title=cAMP-mediated inhibition of the epithelial brush border Na+/H+ exchanger, NHE3, requires an associated regulatory protein. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=94 |issue= 7 |pages= 3010–5 |year= 1997 |pmid= 9096337 |doi=10.1073/pnas.94.7.3010  | pmc=20313 }}
| citations =
*{{cite journal  |vauthors=Reczek D, Berryman M, Bretscher A |title=Identification of EBP50: A PDZ-containing phosphoprotein that associates with members of the ezrin-radixin-moesin family. |journal=J. Cell Biol. |volume=139 |issue= 1 |pages= 169–79 |year= 1998 |pmid= 9314537 |doi=10.1083/jcb.139.1.169  | pmc=2139813  }}
*{{cite journal | author=Poulat F, Barbara PS, Desclozeaux M, ''et al.'' |title=The human testis determining factor SRY binds a nuclear factor containing PDZ protein interaction domains. |journal=J. Biol. Chem. |volume=272 |issue= 11 |pages= 7167-72 |year= 1997 |pmid= 9054412 |doi=  }}
*{{cite journal  |vauthors=Yun CH, Lamprecht G, Forster DV, Sidor A |title=NHE3 kinase A regulatory protein E3KARP binds the epithelial brush border Na+/H+ exchanger NHE3 and the cytoskeletal protein ezrin. |journal=J. Biol. Chem. |volume=273 |issue= 40 |pages= 25856–63 |year= 1998 |pmid= 9748260 |doi=10.1074/jbc.273.40.25856  }}
*{{cite journal  | author=Yun CH, Oh S, Zizak M, ''et al.'' |title=cAMP-mediated inhibition of the epithelial brush border Na+/H+ exchanger, NHE3, requires an associated regulatory protein. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=94 |issue= 7 |pages= 3010-5 |year= 1997 |pmid= 9096337 |doi= }}
*{{cite journal   |vauthors=Imai K, Sarker AH, Akiyama K, etal |title=Genomic structure and sequence of a human homologue (NTHL1/NTH1) of Escherichia coli endonuclease III with those of the adjacent parts of TSC2 and SLC9A3R2 genes. |journal=Gene |volume=222 |issue= 2 |pages= 287–95 |year= 1999 |pmid= 9831664 |doi=10.1016/S0378-1119(98)00485-5  }}
*{{cite journal  | author=Reczek D, Berryman M, Bretscher A |title=Identification of EBP50: A PDZ-containing phosphoprotein that associates with members of the ezrin-radixin-moesin family. |journal=J. Cell Biol. |volume=139 |issue= 1 |pages= 169-79 |year= 1998 |pmid= 9314537 |doi= }}
*{{cite journal   |vauthors=Zizak M, Lamprecht G, Steplock D, etal |title=cAMP-induced phosphorylation and inhibition of Na(+)/H(+) exchanger 3 (NHE3) are dependent on the presence but not the phosphorylation of NHE regulatory factor. |journal=J. Biol. Chem. |volume=274 |issue= 35 |pages= 24753–8 |year= 1999 |pmid= 10455146 |doi=10.1074/jbc.274.35.24753 }}
*{{cite journal | author=Hall RA, Ostedgaard LS, Premont RT, ''et al.'' |title=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. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=95 |issue= 15 |pages= 8496-501 |year= 1998 |pmid= 9671706 |doi= }}
*{{cite journal   |vauthors=Hwang JI, Heo K, Shin KJ, etal |title=Regulation of phospholipase C-beta 3 activity by Na+/H+ exchanger regulatory factor 2. |journal=J. Biol. Chem. |volume=275 |issue= 22 |pages= 16632–7 |year= 2000 |pmid= 10748023 |doi= 10.1074/jbc.M001410200 }}
*{{cite journal | author=Yun CH, Lamprecht G, Forster DV, Sidor A |title=NHE3 kinase A regulatory protein E3KARP binds the epithelial brush border Na+/H+ exchanger NHE3 and the cytoskeletal protein ezrin. |journal=J. Biol. Chem. |volume=273 |issue= 40 |pages= 25856-63 |year= 1998 |pmid= 9748260 |doi=  }}
*{{cite journal   |vauthors=Sun F, Hug MJ, Lewarchik CM, etal |title=E3KARP mediates the association of ezrin and protein kinase A with the cystic fibrosis transmembrane conductance regulator in airway cells. |journal=J. Biol. Chem. |volume=275 |issue= 38 |pages= 29539–46 |year= 2000 |pmid= 10893422 |doi= 10.1074/jbc.M004961200 }}
*{{cite journal | author=Imai K, Sarker AH, Akiyama K, ''et al.'' |title=Genomic structure and sequence of a human homologue (NTHL1/NTH1) of Escherichia coli endonuclease III with those of the adjacent parts of TSC2 and SLC9A3R2 genes. |journal=Gene |volume=222 |issue= 2 |pages= 287-95 |year= 1999 |pmid= 9831664 |doi= }}
*{{cite journal   |vauthors=Kanai F, Marignani PA, Sarbassova D, etal |title=TAZ: a novel transcriptional co-activator regulated by interactions with 14-3-3 and PDZ domain proteins. |journal=EMBO J. |volume=19 |issue= 24 |pages= 6778–91 |year= 2001 |pmid= 11118213 |doi= 10.1093/emboj/19.24.6778  | pmc=305881 }}
*{{cite journal | author=Zizak M, Lamprecht G, Steplock D, ''et al.'' |title=cAMP-induced phosphorylation and inhibition of Na(+)/H(+) exchanger 3 (NHE3) are dependent on the presence but not the phosphorylation of NHE regulatory factor. |journal=J. Biol. Chem. |volume=274 |issue= 35 |pages= 24753-8 |year= 1999 |pmid= 10455146 |doi= }}
*{{cite journal  |vauthors=Reczek D, Bretscher A |title=Identification of EPI64, a TBC/rabGAP domain-containing microvillar protein that binds to the first PDZ domain of EBP50 and E3KARP. |journal=J. Cell Biol. |volume=153 |issue= 1 |pages= 191–206 |year= 2001 |pmid= 11285285 |doi=10.1083/jcb.153.1.191  | pmc=2185518  }}
*{{cite journal | author=Hwang JI, Heo K, Shin KJ, ''et al.'' |title=Regulation of phospholipase C-beta 3 activity by Na+/H+ exchanger regulatory factor 2. |journal=J. Biol. Chem. |volume=275 |issue= 22 |pages= 16632-7 |year= 2000 |pmid= 10748023 |doi= 10.1074/jbc.M001410200 }}
*{{cite journal  |vauthors=Takeda T, McQuistan T, Orlando RA, Farquhar MG |title=Loss of glomerular foot processes is associated with uncoupling of podocalyxin from the actin cytoskeleton. |journal=J. Clin. Invest. |volume=108 |issue= 2 |pages= 289–301 |year= 2001 |pmid= 11457882 |doi=10.1172/JCI12539  | pmc=203027  }}
*{{cite journal  | author=Sun F, Hug MJ, Lewarchik CM, ''et al.'' |title=E3KARP mediates the association of ezrin and protein kinase A with the cystic fibrosis transmembrane conductance regulator in airway cells. |journal=J. Biol. Chem. |volume=275 |issue= 38 |pages= 29539-46 |year= 2000 |pmid= 10893422 |doi= 10.1074/jbc.M004961200 }}
*{{cite journal  |vauthors=Yun CC, Chen Y, Lang F |title=Glucocorticoid activation of Na(+)/H(+) exchanger isoform 3 revisited. The roles of SGK1 and NHERF2. |journal=J. Biol. Chem. |volume=277 |issue= 10 |pages= 7676–83 |year= 2002 |pmid= 11751930 |doi= 10.1074/jbc.M107768200 }}
*{{cite journal  | author=Kanai F, Marignani PA, Sarbassova D, ''et al.'' |title=TAZ: a novel transcriptional co-activator regulated by interactions with 14-3-3 and PDZ domain proteins. |journal=EMBO J. |volume=19 |issue= 24 |pages= 6778-91 |year= 2001 |pmid= 11118213 |doi= 10.1093/emboj/19.24.6778 }}
*{{cite journal  |vauthors=DeMarco SJ, Chicka MC, Strehler EE |title=Plasma membrane Ca2+ ATPase isoform 2b interacts preferentially with Na+/H+ exchanger regulatory factor 2 in apical plasma membranes. |journal=J. Biol. Chem. |volume=277 |issue= 12 |pages= 10506–11 |year= 2002 |pmid= 11786550 |doi= 10.1074/jbc.M111616200 }}
*{{cite journal  | author=Reczek D, Bretscher A |title=Identification of EPI64, a TBC/rabGAP domain-containing microvillar protein that binds to the first PDZ domain of EBP50 and E3KARP. |journal=J. Cell Biol. |volume=153 |issue= 1 |pages= 191-206 |year= 2001 |pmid= 11285285 |doi= }}
*{{cite journal  |vauthors=Ingraffea J, Reczek D, Bretscher A |title=Distinct cell type-specific expression of scaffolding proteins EBP50 and E3KARP: EBP50 is generally expressed with ezrin in specific epithelia, whereas E3KARP is not. |journal=Eur. J. Cell Biol. |volume=81 |issue= 2 |pages= 61–8 |year= 2002 |pmid= 11893083 |doi=10.1078/0171-9335-00218  }}
*{{cite journal  | author=Takeda T, McQuistan T, Orlando RA, Farquhar MG |title=Loss of glomerular foot processes is associated with uncoupling of podocalyxin from the actin cytoskeleton. |journal=J. Clin. Invest. |volume=108 |issue= 2 |pages= 289-301 |year= 2001 |pmid= 11457882 |doi= }}
*{{cite journal   |vauthors=Kim JH, Lee-Kwon W, Park JB, etal |title=Ca(2+)-dependent inhibition of Na+/H+ exchanger 3 (NHE3) requires an NHE3-E3KARP-alpha-actinin-4 complex for oligomerization and endocytosis. |journal=J. Biol. Chem. |volume=277 |issue= 26 |pages= 23714–24 |year= 2002 |pmid= 11948184 |doi= 10.1074/jbc.M200835200 }}
*{{cite journal  | author=Yun CC, Chen Y, Lang F |title=Glucocorticoid activation of Na(+)/H(+) exchanger isoform 3 revisited. The roles of SGK1 and NHERF2. |journal=J. Biol. Chem. |volume=277 |issue= 10 |pages= 7676-83 |year= 2002 |pmid= 11751930 |doi= 10.1074/jbc.M107768200 }}
*{{cite journal  |vauthors=Li Y, Li J, Straight SW, Kershaw DB |title=PDZ domain-mediated interaction of rabbit podocalyxin and Na(+)/H(+) exchange regulatory factor-2. |journal=Am. J. Physiol. Renal Physiol. |volume=282 |issue= 6 |pages= F1129–39 |year= 2002 |pmid= 11997330 |doi= 10.1152/ajprenal.00131.2001 }}
*{{cite journal | author=DeMarco SJ, Chicka MC, Strehler EE |title=Plasma membrane Ca2+ ATPase isoform 2b interacts preferentially with Na+/H+ exchanger regulatory factor 2 in apical plasma membranes. |journal=J. Biol. Chem. |volume=277 |issue= 12 |pages= 10506-11 |year= 2002 |pmid= 11786550 |doi= 10.1074/jbc.M111616200 }}
*{{cite journal  |vauthors=Mahon MJ, Donowitz M, Yun CC, Segre GV |title=Na(+)/H(+ ) exchanger regulatory factor 2 directs parathyroid hormone 1 receptor signalling. |journal=Nature |volume=417 |issue= 6891 |pages= 858–61 |year= 2002 |pmid= 12075354 |doi= 10.1038/nature00816 }}
*{{cite journal  | author=Ingraffea J, Reczek D, Bretscher A |title=Distinct cell type-specific expression of scaffolding proteins EBP50 and E3KARP: EBP50 is generally expressed with ezrin in specific epithelia, whereas E3KARP is not. |journal=Eur. J. Cell Biol. |volume=81 |issue= 2 |pages= 61-8 |year= 2002 |pmid= 11893083 |doi= }}
*{{cite journal   |vauthors=Sitaraman SV, Wang L, Wong M, etal |title=The adenosine 2b receptor is recruited to the plasma membrane and associates with E3KARP and Ezrin upon agonist stimulation. |journal=J. Biol. Chem. |volume=277 |issue= 36 |pages= 33188–95 |year= 2002 |pmid= 12080047 |doi= 10.1074/jbc.M202522200 }}
*{{cite journal  | author=Kim JH, Lee-Kwon W, Park JB, ''et al.'' |title=Ca(2+)-dependent inhibition of Na+/H+ exchanger 3 (NHE3) requires an NHE3-E3KARP-alpha-actinin-4 complex for oligomerization and endocytosis. |journal=J. Biol. Chem. |volume=277 |issue= 26 |pages= 23714-24 |year= 2002 |pmid= 11948184 |doi= 10.1074/jbc.M200835200 }}
*{{cite journal   |vauthors=Lamprecht G, Heil A, Baisch S, etal |title=The down regulated in adenoma (dra) gene product binds to the second PDZ domain of the NHE3 kinase A regulatory protein (E3KARP), potentially linking intestinal Cl-/HCO3- exchange to Na+/H+ exchange. |journal=Biochemistry |volume=41 |issue= 41 |pages= 12336–42 |year= 2002 |pmid= 12369822 |doi=10.1021/bi0259103 }}
*{{cite journal | author=Li Y, Li J, Straight SW, Kershaw DB |title=PDZ domain-mediated interaction of rabbit podocalyxin and Na(+)/H(+) exchange regulatory factor-2. |journal=Am. J. Physiol. Renal Physiol. |volume=282 |issue= 6 |pages= F1129-39 |year= 2002 |pmid= 11997330 |doi= 10.1152/ajprenal.00131.2001 }}
{{Refend}}
*{{cite journal | author=Mahon MJ, Donowitz M, Yun CC, Segre GV |title=Na(+)/H(+ ) exchanger regulatory factor 2 directs parathyroid hormone 1 receptor signalling. |journal=Nature |volume=417 |issue= 6891 |pages= 858-61 |year= 2002 |pmid= 12075354 |doi= 10.1038/nature00816 }}
*{{cite journal  | author=Sitaraman SV, Wang L, Wong M, ''et al.'' |title=The adenosine 2b receptor is recruited to the plasma membrane and associates with E3KARP and Ezrin upon agonist stimulation. |journal=J. Biol. Chem. |volume=277 |issue= 36 |pages= 33188-95 |year= 2002 |pmid= 12080047 |doi= 10.1074/jbc.M202522200 }}
*{{cite journal  | author=Lamprecht G, Heil A, Baisch S, ''et al.'' |title=The down regulated in adenoma (dra) gene product binds to the second PDZ domain of the NHE3 kinase A regulatory protein (E3KARP), potentially linking intestinal Cl-/HCO3- exchange to Na+/H+ exchange. |journal=Biochemistry |volume=41 |issue= 41 |pages= 12336-42 |year= 2002 |pmid= 12369822 |doi= }}
}}
{{refend}}


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{{NLM content}}
{{NLM content}}
{{PDB Gallery|geneid=9351}}
{{Membrane transport proteins}}
{{Membrane transport proteins}}
[[Category:Solute carrier family]]
[[Category:Solute carrier family]]
{{WH}}
[[Category:Membrane proteins]]
{{WS}}

Latest revision as of 00:32, 27 October 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Sodium-hydrogen exchange regulatory cofactor NHE-RF2 (NHERF-2) also known as tyrosine kinase activator protein 1 (TKA-1) or SRY-interacting protein 1 (SIP-1) is a protein that in humans is encoded by the SLC9A3R2 (solute carrier family 9 isoform A3 regulatory factor 2) gene.[1][2]

NHERF-2) is a 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. It is necessary for cAMP-mediated phosphorylation and inhibition of SLC9A3. In addition, it may also act as scaffold protein in the nucleus.

Function

This regulatory protein (factor) interacts with a sodium/hydrogen exchanger NHE3 (SLC9A3) in the brush border membrane of the proximal tubule, small intestine, and colon that plays a major role in transepithelial sodium absorption. SLC9A3R2, as well as SLC9A3R1 and protein kinase A phosphorylation, may play a role in NHE3 regulation.[3]

Interactions

Sodium-hydrogen exchange regulatory cofactor 2 has been shown to interact with SGK,[4][5] Actinin alpha 4,[6] Parathyroid hormone receptor 1,[7] Phosphoinositide-dependent kinase-1,[4] EZR,[8][9] PODXL,[10][11][12] Cystic fibrosis transmembrane conductance regulator[13] and PLCB3.[14]

See also

References

  1. ↑ Poulat F, de Santa Barbara P, Desclozeaux M, Soullier S, Moniot B, Bonneaud N, Boizet B, Berta P (March 1997). "The human testis determining factor SRY binds a nuclear factor containing PDZ protein interaction domains". J. Biol. Chem. 272 (11): 7167–72. doi:10.1074/jbc.272.11.7167. PMID 9054412.
  2. ↑ Hall RA, Ostedgaard LS, Premont RT, Blitzer JT, Rahman N, Welsh MJ, Lefkowitz RJ (July 1998). "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. doi:10.1073/pnas.95.15.8496. PMC 21104. PMID 9671706.
  3. ↑ "Entrez Gene: SLC9A3R2 solute carrier family 9 (sodium/hydrogen exchanger), member 3 regulator 2".
  4. ↑ 4.0 4.1 Chun, Jaesun; Kwon Taegun; Lee Eunjung; Suh Pann-Ghill; Choi Eui-Ju; Sun Kang Sang (October 2002). "The Na(+)/H(+) exchanger regulatory factor 2 mediates phosphorylation of serum- and glucocorticoid-induced protein kinase 1 by 3-phosphoinositide-dependent protein kinase 1". Biochem. Biophys. Res. Commun. United States. 298 (2): 207–15. doi:10.1016/S0006-291X(02)02428-2. ISSN 0006-291X. PMID 12387817.
  5. ↑ Yun, C Chris; Chen Yueping; Lang Florian (March 2002). "Glucocorticoid activation of Na(+)/H(+) exchanger isoform 3 revisited. The roles of SGK1 and NHERF2". J. Biol. Chem. United States. 277 (10): 7676–83. doi:10.1074/jbc.M107768200. ISSN 0021-9258. PMID 11751930.
  6. ↑ Kim JH, Lee-Kwon W, Park JB, Ryu SH, Yun CH, Donowitz M (June 2002). "Ca(2+)-dependent inhibition of Na+/H+ exchanger 3 (NHE3) requires an NHE3-E3KARP-alpha-actinin-4 complex for oligomerization and endocytosis". J. Biol. Chem. United States. 277 (26): 23714–24. doi:10.1074/jbc.M200835200. ISSN 0021-9258. PMID 11948184.
  7. ↑ Mahon, Matthew J; Donowitz Mark; Yun C Chris; Segre Gino V (June 2002). "Na(+)/H(+ ) exchanger regulatory factor 2 directs parathyroid hormone 1 receptor signalling". Nature. England. 417 (6891): 858–61. doi:10.1038/nature00816. ISSN 0028-0836. PMID 12075354.
  8. ↑ Yun, C H; Lamprecht G; Forster D V; Sidor A (October 1998). "NHE3 kinase A regulatory protein E3KARP binds the epithelial brush border Na+/H+ exchanger NHE3 and the cytoskeletal protein ezrin". J. Biol. Chem. UNITED STATES. 273 (40): 25856–63. doi:10.1074/jbc.273.40.25856. ISSN 0021-9258. PMID 9748260.
  9. ↑ Sitaraman, Shanthi V; Wang Lixin; Wong Michelle; Bruewer Matthias; Hobert Michael; Yun C-H; Merlin Didier; Madara James L (September 2002). "The adenosine 2b receptor is recruited to the plasma membrane and associates with E3KARP and Ezrin upon agonist stimulation". J. Biol. Chem. United States. 277 (36): 33188–95. doi:10.1074/jbc.M202522200. ISSN 0021-9258. PMID 12080047.
  10. ↑ Meder, Doris; Shevchenko Anna; Simons Kai; Füllekrug Joachim (January 2005). "Gp135/podocalyxin and NHERF-2 participate in the formation of a preapical domain during polarization of MDCK cells". J. Cell Biol. United States. 168 (2): 303–13. doi:10.1083/jcb.200407072. ISSN 0021-9525. PMC 2171597. PMID 15642748.
  11. ↑ Takeda, T; McQuistan T; Orlando R A; Farquhar M G (July 2001). "Loss of glomerular foot processes is associated with uncoupling of podocalyxin from the actin cytoskeleton". J. Clin. Invest. United States. 108 (2): 289–301. doi:10.1172/JCI12539. ISSN 0021-9738. PMC 203027. PMID 11457882.
  12. ↑ Li, Yong; Li Jian; Straight Samuel W; Kershaw David B (June 2002). "PDZ domain-mediated interaction of rabbit podocalyxin and Na(+)/H(+) exchange regulatory factor-2". Am. J. Physiol. Renal Physiol. United States. 282 (6): F1129–39. doi:10.1152/ajprenal.00131.2001. ISSN 0363-6127. PMID 11997330.
  13. ↑ Sun, F; Hug M J; Lewarchik C M; Yun C H; Bradbury N A; Frizzell R A (September 2000). "E3KARP mediates the association of ezrin and protein kinase A with the cystic fibrosis transmembrane conductance regulator in airway cells". J. Biol. Chem. UNITED STATES. 275 (38): 29539–46. doi:10.1074/jbc.M004961200. ISSN 0021-9258. PMID 10893422.
  14. ↑ Hwang, J I; Heo K; Shin K J; Kim E; Yun C; Ryu S H; Shin H S; Suh P G (June 2000). "Regulation of phospholipase C-beta 3 activity by Na+/H+ exchanger regulatory factor 2". J. Biol. Chem. UNITED STATES. 275 (22): 16632–7. doi:10.1074/jbc.M001410200. ISSN 0021-9258. PMID 10748023.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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