Sodium-hydrogen exchange regulatory cofactor 2

Last updated

SLC9A3R2
Protein SLC9A3R2 PDB 2he4.png
Available structures
PDB Ortholog search: PDBe RCSB
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
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001130012
NM_001252073
NM_001252075
NM_001252076
NM_004785

Contents

NM_023055
NM_023449
NM_001357796

RefSeq (protein)

NP_001123484
NP_001239002
NP_001239004
NP_001239005
NP_004776

NP_075542
NP_075938
NP_001344725

Location (UCSC) Chr 16: 2.03 – 2.04 Mb Chr 17: 24.86 – 24.87 Mb
PubMed search [3] [4]
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]

See also

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000065054 Ensembl, May 2017
  2. 1 2 3 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.
  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.
  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".
  8. 1 2 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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.

Further reading

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