The phosphoinositide binding Phox Homology domain of Sorting Nexin 15-like proteins
The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Members of this subfamily have similarity to sorting nexin 15 (SNX15), which contains an N-terminal PX domain and a C-terminal Microtubule Interacting and Trafficking (MIT) domain. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNX15 plays a role in protein trafficking processes in the endocytic pathway and the trans-Golgi network. The PX domain of SNX15 interacts with the PDGF receptor and is responsible for the membrane association of the protein. Other members of this subfamily contain an additional C-terminal kinase domain, similar to human RPK118, which binds sphingosine kinase and the antioxidant peroxiredoxin-3 (PRDX3). RPK118 may be involved in the transport of proteins such as PRDX3 from the cytoplasm to its site of function in the mitochondria.
Feature 1:phosphoinositide binding site [chemical binding site]
Comment:A majority of PX domain containing proteins binds phosphatidylinositol-3-phosphate (PI3P) at this site. In some cases, other phosphoinositides, such as PI4P or PI(3,4)P2, are the preferred substrates.
Comment:based on the structures of phosphatidylinositol-3-phosphate bound to other members of this superfamily
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.