NHERF2

SLC9A3R2
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2D11, 2HE4, 2OCS, 4P0C
Identifiers
Aliases	SLC9A3R2, E3KARP, NHE3RF2, NHERF-2, NHERF2, OCTS2, SIP-1, SIP1, TKA-1, Sodium-hydrogen exchange regulatory cofactor 2, SLC9A3 regulator 2
External IDs	OMIM: 606553; MGI: 1890662; HomoloGene: 56962; GeneCards: SLC9A3R2; OMA: SLC9A3R2 - orthologs
Gene location ( Human)
Chr.	Chromosome 16 (human)
End	2,039,026 bp
Gene location ( Mouse)
Chr.	Chromosome 17 (mouse)
End	24,869,301 bp
RNA expression pattern
	Top expressed in
	apex of heart; ; right lung; ; right lobe of liver; ; upper lobe of left lung; ; right lobe of thyroid gland; ; right auricle; ; right coronary artery; ; left lobe of thyroid gland; ; left uterine tube; ; left coronary artery;
	Top expressed in
	external carotid artery; ; aortic valve; ; motor neuron; ; internal carotid artery; ; ascending aorta; ; right lung; ; right lung lobe; ; carotid body; ; left lung; ; right ventricle;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	molecular adaptor activity; phosphatase binding; beta-catenin binding; signaling receptor binding; protein C-terminus binding; protein binding; cadherin binding;
Cellular component	plasma membrane; extracellular exosome; apical plasma membrane; membrane; endomembrane system; nucleus; focal adhesion;
Biological process	protein-containing complex assembly;
	Sources: Amigo / QuickGO
Orthologs
	9351
	65962
	ENSG00000065054
	ENSMUSG00000002504
	Q15599
	Q9JHL1
	NM_001130012; NM_001252073; NM_001252075; NM_001252076; NM_004785
	NM_023055; NM_023449; NM_001357796
	NP_001123484; NP_001239002; NP_001239004; NP_001239005; NP_004776
	NP_075542; NP_075938; NP_001344725
	Wikidata
View/Edit Human	View/Edit Mouse

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.^[5]^[6]

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.^[7]

Interactions

Sodium-hydrogen exchange regulatory cofactor 2 has been shown to interact with SGK,^[8]^[9] Actinin alpha 4,^[10] Parathyroid hormone receptor 1,^[11] Phosphoinositide-dependent kinase-1,^[8] EZR,^[12]^[13] PODXL,^[14]^[15]^[16] Cystic fibrosis transmembrane conductance regulator^[17] and PLCB3.^[18]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000065054 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000002504 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ 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. Bibcode: 1998PNAS...95.8496H. doi: 10.1073/pnas.95.15.8496. PMC 21104. PMID 9671706.
^ "Entrez Gene: SLC9A3R2 solute carrier family 9 (sodium/hydrogen exchanger), member 3 regulator 2".
^ ^a ^b Chun J, 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. 298 (2). United States: 207–15. doi: 10.1016/S0006-291X(02)02428-2. ISSN 0006-291X. PMID 12387817.
^ Yun CC, Chen Yueping, Lang Florian (March 2002). "Glucocorticoid activation of Na(+)/H(+) exchanger isoform 3 revisited. The roles of SGK1 and NHERF2". J. Biol. Chem. 277 (10). United States: 7676–83. doi: 10.1074/jbc.M107768200. ISSN 0021-9258. PMID 11751930.
^ 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. 277 (26). United States: 23714–24. doi: 10.1074/jbc.M200835200. ISSN 0021-9258. PMID 11948184.
^ Mahon MJ, Donowitz Mark, Yun C Chris, Segre Gino V (June 2002). "Na(+)/H(+ ) exchanger regulatory factor 2 directs parathyroid hormone 1 receptor signalling". Nature. 417 (6891). England: 858–61. Bibcode: 2002Natur.417..858M. doi: 10.1038/nature00816. ISSN 0028-0836. PMID 12075354. S2CID 4379134.
^ Yun CH, 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. 273 (40). UNITED STATES: 25856–63. doi: 10.1074/jbc.273.40.25856. ISSN 0021-9258. PMID 9748260.
^ Sitaraman SV, 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. 277 (36). United States: 33188–95. doi: 10.1074/jbc.M202522200. ISSN 0021-9258. PMID 12080047.
^ Meder D, 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. 168 (2). United States: 303–13. doi: 10.1083/jcb.200407072. ISSN 0021-9525. PMC 2171597. PMID 15642748.
^ 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. 108 (2). United States: 289–301. doi: 10.1172/JCI12539. ISSN 0021-9738. PMC 203027. PMID 11457882.
^ Li Y, 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. 282 (6). United States: F1129–39. doi: 10.1152/ajprenal.00131.2001. ISSN 0363-6127. PMID 11997330.
^ 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. 275 (38). UNITED STATES: 29539–46. doi: 10.1074/jbc.M004961200. ISSN 0021-9258. PMID 10893422.
^ Hwang JI, 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. 275 (22). UNITED STATES: 16632–7. doi: 10.1074/jbc.M001410200. ISSN 0021-9258. PMID 10748023.

External links

Overview of all the structural information available in the PDB for UniProt: Q15599 (Na(+)/H(+) exchange regulatory cofactor NHE-RF2) at the PDBe-KB.

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

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000065054 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000002504 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid9054412-5] 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.

[pmid9671706-6] 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. Bibcode: 1998PNAS...95.8496H. doi: 10.1073/pnas.95.15.8496. PMC 21104. PMID 9671706.

[7] "Entrez Gene: SLC9A3R2 solute carrier family 9 (sodium/hydrogen exchanger), member 3 regulator 2".

[pmid12387817-8] Chun J, 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. 298 (2). United States: 207–15. doi: 10.1016/S0006-291X(02)02428-2. ISSN 0006-291X. PMID 12387817.

[pmid11751930-9] Yun CC, Chen Yueping, Lang Florian (March 2002). "Glucocorticoid activation of Na(+)/H(+) exchanger isoform 3 revisited. The roles of SGK1 and NHERF2". J. Biol. Chem. 277 (10). United States: 7676–83. doi: 10.1074/jbc.M107768200. ISSN 0021-9258. PMID 11751930.

[pmid11948184-10] 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. 277 (26). United States: 23714–24. doi: 10.1074/jbc.M200835200. ISSN 0021-9258. PMID 11948184.

[pmid12075354-11] Mahon MJ, Donowitz Mark, Yun C Chris, Segre Gino V (June 2002). "Na(+)/H(+ ) exchanger regulatory factor 2 directs parathyroid hormone 1 receptor signalling". Nature. 417 (6891). England: 858–61. Bibcode: 2002Natur.417..858M. doi: 10.1038/nature00816. ISSN 0028-0836. PMID 12075354. S2CID 4379134.

[pmid9748260-12] Yun CH, 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. 273 (40). UNITED STATES: 25856–63. doi: 10.1074/jbc.273.40.25856. ISSN 0021-9258. PMID 9748260.

[pmid12080047-13] Sitaraman SV, 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. 277 (36). United States: 33188–95. doi: 10.1074/jbc.M202522200. ISSN 0021-9258. PMID 12080047.

[pmid15642748-14] Meder D, 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. 168 (2). United States: 303–13. doi: 10.1083/jcb.200407072. ISSN 0021-9525. PMC 2171597. PMID 15642748.

[pmid11457882-15] 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. 108 (2). United States: 289–301. doi: 10.1172/JCI12539. ISSN 0021-9738. PMC 203027. PMID 11457882.

[pmid11997330-16] Li Y, 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. 282 (6). United States: F1129–39. doi: 10.1152/ajprenal.00131.2001. ISSN 0363-6127. PMID 11997330.

[pmid10893422-17] 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. 275 (38). UNITED STATES: 29539–46. doi: 10.1074/jbc.M004961200. ISSN 0021-9258. PMID 10893422.

[pmid10748023-18] Hwang JI, 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. 275 (22). UNITED STATES: 16632–7. doi: 10.1074/jbc.M001410200. ISSN 0021-9258. PMID 10748023.

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Function

Interactions

See also

References

Further reading

External links

Function

Interactions

See also

References

Further reading

External links

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