GENOMIC STRUCTURE OF HUMAN TRANSCOBALAMIN-II - COMPARISON TO HUMAN INTRINSIC-FACTOR AND TRANSCOBALAMIN-I

Human transcobalamin II (TC II) gene was isolated and partially sequen ced. The gene is composed of nine exons and eight introns spanning sim ilar to 20 kb. Multiple potential transcription start sites were revea led by primer extension analysis. The 5'-flanking region of the gene c ontained no TATA-like motif, but a binding motif for HIP1, which is su ggested to be important in the transcription of TATA-less housekeeping genes, was identified in a region very close to the initiator methion ine codon. In addition, potential binding sites for a variety of trans cription factors such as SP1, AP2, CF1, NF-IL6, Ets-l, Myb and E2A wer e also observed. Comparison of the genomic structure of TC II to other Cbl-binding proteins, human gastric intrinsic factor (IF) and transco balamin I (TC I) revealed similar intron-exon organizations with respe ct to the number, position and size of exons. These results suggest th at TC II, TC I and IF genes have originated by gene duplications of an ancestral gene and TC II, unlike the other two Cbl-binding proteins, is the product of a ''housekeeping'' gene. (C) 1995 Academic Press, In c.