Recombinant Mouse Na (+)/H (+) exchange regulatory cofactor NHE-RF3 (Pdzk1)

Function

A scaffold protein that connects plasma membrane proteins and regulatory components, regulating their surface expression in epithelial cells apical domains. May be involved in the coordination of a diverse range of regulatory processes for ion transport and second messenger cascades. In complex with NHERF1, may cluster proteins that are functionally dependent in a mutual fashion and modulate the trafficking and the activity of the associated membrane proteins. May play a role in the cellular mechanisms associated with multidrug resistance through its interaction with ABCC2 and PDZK1IP1. May potentiate the CFTR chloride channel activity (By similarity). Required for normal cell-surface expression of SCARB1. Plays a role in maintaining normal plasma cholesterol levels via its effects on SCARB1. Plays a role in the normal localization and function of the chloride-anion exchanger SLC26A6 to the plasma membrane in the brush border of the proximal tubule of the kidney. May be involved in the regulation of proximal tubular Na(+)-dependent inorganic phosphate cotransport therefore playing an important role in tubule function

Subcellular Location

Membrane (Peripheral membrane protein); Cell membrane

Tissue Specificity

Expressed in kidney, liver, small intestine. brain, lung, and testis (at protein level)

Subunit

Interacts with PDZK1IP1 and ABCC2. Binds to the C-terminal region of SLC26A3. Interacts (via C-terminal PDZ domain) with SLC26A6 (via C-terminal domain). Interacts (via C-terminal PDZ domain) with SLC9A3 (via C-terminal domain) (By similarity). Component of a complex, composed of PDZK1, SYNGAP1, KLHL17 and NMDA receptors. Interacts (via PDZ1 domain) directly with KLHL17; the interaction is important for integrity of actin cytoskeleton structures in neurons (By similarity). Forms a heterodimeric complex with NHERF1. Interacts with AKAP2, BCR, CFTR, SLCO1A1, SLC22A12, SLC22A4, SLC22A5, SLC26A6, NHERF2 and SLC17A1. Interacts (via the first PDZ domain) with PTGIR (via non-isoprenylated C-terminus). Interacts (via PDZ domains 1 and 3) with SCARB1 (C-terminal domain). Interacts (via PDZ domains 1 and 3) with SLC5A8 (via PDZ-binding motif); interaction increases nicotinate transport activity of SLC5A8 (By similarity)

• Wang S. et al. Accessory protein facilitated CFTR-CFTR interaction, a molecular mechanism to potentiate the chloride channel activity. — Cell (2000)
• Kocher O. et al. Targeted disruption of the PDZK1 gene by homologous recombination. — Mol. Cell. Biol. (2003)
• Carninci P. et al. The transcriptional landscape of the mammalian genome. — Science (2005)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Gisler S.M. et al. Interaction of the type IIa Na/Pi-cotransporter with PDZ proteins. — J. Biol. Chem. (2001)
• Gisler S.M. et al. PDZK1: I. a major scaffolder in brush borders of proximal tubular cells. — Kidney Int. (2003)
• Kato Y. et al. PDZK1 directly regulates the function of organic cation/carnitine transporter OCTN2. — Mol. Pharmacol. (2005)
• Thomson R.B. et al. Role of PDZK1 in membrane expression of renal brush border ion exchangers. — Proc. Natl. Acad. Sci. U.S.A. (2005)