Evolutionary divergence in the broad complex, tramtrack and bric à brac/poxviruses and zinc finger domain from the candidate tumor suppressor gene hypermethylated in cancer.

Hypermethylated in cancer, a new candidate tumor suppressor gene located in 17p13.3, encodes a protein with five Krüppel-like C2H2 zinc finger motifs and a N-terminal protein/protein interaction domain called broad complex, tramtrack and bric à brac/poxviruses and zinc finger domain. Hypermethylated in cancer appears unique in the broad complex, tramtrack and bric à brac/poxviruses and zinc finger family since it contains a 13 amino acid insertion located in a loop between the conserved beta-strand beta5 and helix alpha5 which are involved in dimerization and scaffolding of the broad complex, tramtrack and bric à brac/poxviruses and zinc finger domain. Cloning and sequencing of a murine hypermethylated in cancer gene suggests that this insertion has been acquired late in the evolution since it is present in two mammalian hypermethylated in cancer genes but absent in its zebrafish and avian counterparts. This is a unique example of a high divergence of the same broad complex, tramtrack and bric à brac/poxviruses and zinc finger domain in different species.