CHARACTERIZATION OF THE GENE (VBP1) AND TRANSCRIPT FOR THE VON-HIPPEL-LINDAU BINDING-PROTEIN AND ISOLATION OF THE HIGHLY CONSERVED MURINE HOMOLOG

A single copy, widely expressed gene of at least 30 kb and six exons w as discovered via a hybrid mRNA resulting from an inversion causing he mophilia A. A segment of the 1.7-kb message of this gene has been show n by others to encode a protein (named VBP1) interacting with the prod uct of the von Hippel-Lindau gene and thus is expected to participate in pathways involving this tumor suppressor gene, The mouse VBP1 messa ge we isolated encodes a polypeptide of 160 residues absolutely identi cal to that of human. Even the 3' untranslated tails of the mRNAs show 68% conservation, and both use the unusual ATTAAA polyadenylation sig nal, The mouse gene has a single transcription start while the human h omologue has two major starts and a minor start. This could result in amino-end extensions of the human protein. A polymorphism with 42% het erozygosity in the United Kingdom population was detected in the 3' ta il of the message. VBP1 is unlike other known proteins but a consensus for tyrosine phosphorylation possibly suggests regulation by kinases. (C) 1997 Academic Press.