STRUCTURAL ORGANIZATION AND CHROMOSOMAL LOCALIZATION OF A HUMAN GENE (HIP PAP) ENCODING A C-TYPE LECTIN OVEREXPRESSED IN PRIMARY LIVER-CANCER/

We previously identified, through differential screening of a human pr imary liver cancer library, a novel gene (named HIP) the expression of which is markedly increased in 25% of human primary liver cancers. HI P mRNA expression is tissue specific since it is restricted to pancrea s and small intestine. HIP protein consists in a signal peptide linked to a carbohydrate-recognition domain (CRD), typical of C-type lectins without other binding domains. We have proposed that HIP and related proteins belong to a new family of C-type lectins. Drickamer [Drickame r, K. (1993) Curr. Opin. Struct. Biol. 3,393-400] included this group of proteins in his classification of C-type lectins as the free CRD (g roup VII) lectins. In the present report we describe the genomic organ ization and the chromosomal localization of HIP We have shown that HIP is in fact the pancreatitis-associated protein (PAP) and provided a p hylogenetic analysis of the free CRD lectins. Furthermore, the analy s is of HIP/PAP gene indicates that the HIP/PAP CRD is encoded by four e xons, a pattern shared with all members of this group of proteins. Thi s common intron-exon organization indicates an ancient divergence of t he free CRD-lectin group from other groups of C-type lectins. We provi de evidence for the localization of HIP/PAP on chromosome 2, suggestin g previous duplication of HIP/PAP and the related reg I alpha and reg I beta genes from the same ancestral gene. Finally, the sequence of th e 5' upstream region of the HIP gene shows several potential regulator y elements which might account for the enhanced expression of the gene during pancreatic inflammation and liver carcinogenesis.