Sodium-hydrogen exchange regulatory cofactor 2

Solute carrier family 9 (sodium/hydrogen exchanger), member 3 regulator 2

PDB rendering based on 2he4.
Symbols SLC9A3R2; E3KARP; MGC104639; NHE3RF2; NHERF-2; NHERF2; OCTS2; SIP-1; SIP1; TKA-1
External IDs OMIM606553 MGI1890662 HomoloGene56962 GeneCards: SLC9A3R2 Gene
RNA expression pattern
PBB GE SLC9A3R2 209830 s at tn.png
More reference expression data
Species Human Mouse
Entrez 9351 65962
Ensembl ENSG00000065054 ENSMUSG00000002504
UniProt Q15599 Q9JHL1
RefSeq (mRNA) NM_001130012.1 NM_023055
RefSeq (protein) NP_001123484.1 NP_075542
Location (UCSC) Chr 16:
2.08 – 2.09 Mb
Chr 17:
24.78 – 24.79 Mb
PubMed search [1] [2]

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.



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]


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


  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. ^ a b Chun, Jaesun; Kwon Taegun, Lee Eunjung, Suh Pann-Ghill, Choi Eui-Ju, Sun Kang Sang (Oct. 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 (Mar. 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, Jae Ho; Lee-Kwon Whaseon, Park Jong Bae, Ryu Sung Ho, Yun C H Chris, Donowitz Mark (Jun. 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 (Jun. 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 (Oct. 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 (Sep. 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 (Jan. 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 (Jul. 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 (Jun. 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 (Sep. 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 (Jun. 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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