MOLECULAR-CLONING OF A NOVEL HUMAN GENE ENCODING A 63-KDA PROTEIN ANDITS SUBLOCALIZATION WITHIN THE 11Q13 LOCUS

A human cDNA previously isolated by virtue of its ability to complemen t partially the ultraviolet sensitivity of a xeroderma pigmentosum cel l line was further characterized. The transcription unit is expressed as a single 4.0-kb mRNA that encodes a novel 63-kDa cytoplasmic protei n, possibly initiating from an internal AUG codon. The gene encoding t his protein, named UVRAG, has been extremely well conserved during evo lution, implying an important role for this gene product in cell metab olism, The transcribed mRNA is constitutively expressed in a wide vari ety of human tissues. The protein encoded by this gene is predicted to contain a coiled-coil structure and is likely to be metabolically uns table based on the occurrence of a strong PEST domain. UVRAG was assig ned to human chromosome 11 by Southern hybridization to a somatic cell hybrid panel. Fluorescence in situ hybridization coupled with PCR ana lysis of human/rodent somatic cell hybrids containing segments of huma n chromosome 11 has localized this gene to a subregion of 11q13 in bet ween the D11S916 and the D11S906 loci, Importantly, this region has be en shown to be amplified in a variety of human malignancies, including breast cancer. (C) 1997 Academic Press.