PDZK1 (4th domain)
PDZK1 (4th domain): Human PDZ domain containing 1 (4th PDZ domain)
PDB Code: 2VSP
PDZK1 is a protein that consists of 4 tandem PDZ domains. As such it is a scaffold protein that connects plasma membrane proteins and regulatory components, regulating their surface expression in epithelial cells apical domains. It has been proposed to be involved in the coordination of a diverse range of regulatory processes for ion transport and second messenger cascades like regulation of proximal tubular Na(+)-dependent inorganic phosphate or cellular mechanisms associated with multidrug resistance through its interaction with ABCC2 and PDZK1IP1. PDZK1 has also been proposed to potentiate CFTR chloride channel activity and function to connect SCARB1 with the cellular machineries for intracellular cholesterol transport and/or metabolism. It plays a physiologically role in both oligopeptide handling as well as peptide-like drug transport in the human kidney and has been suggested in regulation of tubule function via regulation of phosphate cotransport . In addition PDZK1 is required for HDL/SR-BI signaling in endothelium and is involved in the maintenance of endothelial monolayer integrity.
Overexpression of PDZK1 has been found in several tumors of epithelial origin and estrogen receptor positive breast cancer and is likely to be associated with drug-resistance phenotype in multiple myeloma.
PDZK1 knockout mice do not have a gross anatomical phenotype but have elevated levels of cholesterol due to a defect in membrane expression of the scavenger receptor ((Kocher et al., 2003b) (Kocher et al., 2003a)). When these mice are challenged with a high phosphate diet, they show decreased NaPi-IIa expression and increased renal phosphate excretion compared with the wild-type animals.
Here we present the structure of the PDZ domain of human PDZ containing 1.
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