The hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) is a zinc-finger protein that interacts with STAM and undergoes tyrosine phosphorylation in response to IL2, CSF2 or HGF. Hrs is involved in intracellular trafficking and signal transduction and is associated with early endosomes. H contains a phosphatidylinositol 3-phosphate-binding domain that contributes to its endosomal targeting, where Hrs colocalizes with Clathrin via a Clathrin box motif at the carboxy terminus of Hrs. Hrs is essential for ventral folding morphogenesis and shares structual similarity to the yeast protein Vps27p, which is involved in vacuolar protein sorting. The human Hrs gene, which maps to chromosome 17q25, enodes a 777 amino acid protein. In Schwann cells, Hrs colocalizes at endosomes with the tumor suppressor protein schwannomin, suggesting a role for schwannomin in Hrs-mediated cell signaling.