THE HUMAN HIP GENE, OVEREXPRESSED IN PRIMARY LIVER-CANCER ENCODES FORA C-TYPE CARBOHYDRATE-BINDING PROTEIN WITH LACTOSE BINDING-ACTIVITY

HIP was originally identified as a gene expressed in primary liver can cers, and in normal tissues such as pancreas and small intestine. Base d on gene data base homologies, the HIP protein should consist of a si gnal peptide linked to a single carbohydrate recognition domain. To te st this hypothesis HIP and the putative carbohydrate recognition domai n encoded by the last 138 C-terminal amino acids, were expressed as gl utathione-S-transferase proteins (GST-HIP and GST-HIP-142, respectivel y). Both recombinant proteins were purified by a single affinity purif ication step from bacterial lysates and their ability to bind sacchari des coupled to trisacryl GF 2000M were tested. Our results show that H IP and HIP-142 proteins bind to lactose, moreover the binding requires divalent cations. Thus the HIP protein is a lactose-binding lectin wi th the characteristics of a C-type carbohydrate recognition domain of 138 amino acids in the C-terminal region.