Sodium-hydrogen exchange regulatory cofactor NHE-RF2 (NHERF2)

Sodium-hydrogen exchange regulatory cofactor NHE-RF2 (NHERF2) is a PDZ domain-containing scaffold protein encoded by the SLC9A3R2 gene. It organizes membrane protein complexes by connecting plasma membrane proteins (such as NHE3 and CFTR) with cytoskeletal proteins from the ezrin/moesin/radixin family, linking them to the actin cytoskeleton and regulating their membrane expression and function[4][7]. NHERF2 is crucial for cAMP-mediated phosphorylation and inhibition of the sodium/hydrogen exchanger NHE3, thus playing a significant role in intestinal and renal sodium absorption and homeostasis[4][7]. It may also act as a nuclear scaffold protein[4]. Its interactions regulate cystic fibrosis transmembrane conductance regulator (CFTR) activity, calcium signaling via mGluR5, cell adhesion, and cell proliferation[2][5][1]. NHERF2 is implicated in several diseases through these functions, most notably cystic fibrosis and vascular/endothelial disorders[7][5]. Disruption or modulation of NHERF2 scaffolding interactions has been proposed for therapeutic intervention in CFTR-related diseases and inflammation[1][3].

Other names

Na(+)/H(+) exchange regulatory cofactor NHE-RF2SLC9A3R2NHERF-2SIP-1TKA-1E3KARP (NHE3 kinase A regulatory protein)SRY-interacting protein 1Sodium-hydrogen exchanger regulatory factor 2Solute carrier family 9 isoform A3 regulatory factor 2Tyrosine kinase activator protein 1OCTS2NHE3RF2

Modulation/Disruption of PDZ domain-mediated scaffolding to alter protein complex formation and downstream signaling; Inhibition or enhancement of binding to cystic fibrosis transmembrane conductance regulator to regulate chloride transport; Targeting its interaction with NHE3 to alter sodium absorption.