Hexokinase 2 (Hxk2) from Saccharomyces cerevisiae was one of the first metabolic enzymes described as a multifunctional protein. Hxk2 has a double subcellular localization, it functions as a glycolytic enzyme in the cytoplasm and as a regulator of gene transcription of several Mig1-regulated genes in the nucleus. However, the mechanism by which Hxk2 enters and leaves the nucleus is still unknown. In low-glucose conditions, Hxk2 is phosphorylated at serine-14, but how this phosphorylation may affect glucose signalling is also unknown at the moment. Here, we report that the Hxk2 protein is an export substrate of the carrier protein Xpo1(Crm1). We also show that the Hxk2 nuclear export and the binding of Hxk2 and Xpo1 involve two leucine-rich NES, located between leucine-23 and isoleucine-33 (NES1) and leucine-310 and leucine-318 (NES2). We also show that the Hxk2 phosphorylation at serine-14 promotes Hxk2 export by facilitating the association of Hxk2 with Xpo1. Our study uncovers a new cargo for the Xpo1 yeast exportin and identifies Hxk2 phosphorylation at serine-14 as a regulatory mechanism that controls its nuclear exit in function of the glucose levels.
|Evidence ID||Analyze ID||Interactor||Interactor Systematic Name||Interactor||Interactor Systematic Name||Type||Assay||Annotation||Action||Modification||Phenotype||Source||Reference||Note|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Gene Ontology Term||Gene Ontology Term ID||Qualifier||Aspect||Method||Evidence||Source||Assigned On||Annotation Extension||Reference|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Assay||Construct||Conditions||Strain Background||Reference|