The phosphoinositide binding Phox Homology Domain of Cytokine-Independent Survival Kinase
The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Cytokine-independent survival kinase (CISK), also called Serum- and Glucocorticoid-induced Kinase 3 (SGK3), plays a role in cell growth and survival. It is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. CISK/SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. N-terminal to a catalytic kinase domain, CISK contains a PX domain which binds highly phosphorylated PIs, directs membrane localization, and regulates the enzyme's activity.
Feature 1:phosphoinositide binding site [chemical binding site]
Evidence:
Comment:The PX domain of CISK targets highly phosphorylated phosphoinositides such as phosphatidylinositol-3,5-bisphosphate (PI(3,5)P2) and PI(3,4,5)P3.
Comment:Two basic residues are key in binding with phosphoinositides: one forms hydrogen bonds with the 3-phosphate of PI(3)P and another forms hydrogen bonds with the 4-and 5-hydroxyl groups of PI(3)P.
Jiyao W et al.(2023). "The conserved domain database in 2023.",