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 actincytoskeleton 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]
^ abChun, 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. 298 (2). United States: 207–15. doi:10.1016/S0006-291X(02)02428-2. ISSN0006-291X. PMID12387817.
^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. 282 (6). United States: F1129–39. doi:10.1152/ajprenal.00131.2001. ISSN0363-6127. PMID11997330.
Imai K, Sarker AH, Akiyama K, et al. (1999). "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". Gene. 222 (2): 287–95. doi:10.1016/S0378-1119(98)00485-5. PMID9831664.
Ingraffea J, Reczek D, Bretscher A (2002). "Distinct cell type-specific expression of scaffolding proteins EBP50 and E3KARP: EBP50 is generally expressed with ezrin in specific epithelia, whereas E3KARP is not". Eur. J. Cell Biol. 81 (2): 61–8. doi:10.1078/0171-9335-00218. PMID11893083.
Li Y, Li J, Straight SW, Kershaw DB (2002). "PDZ domain-mediated interaction of rabbit podocalyxin and Na(+)/H(+) exchange regulatory factor-2". Am. J. Physiol. Renal Physiol. 282 (6): F1129–39. doi:10.1152/ajprenal.00131.2001. PMID11997330.
Lamprecht G, Heil A, Baisch S, et al. (2002). "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". Biochemistry. 41 (41): 12336–42. doi:10.1021/bi0259103. PMID12369822.
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.