CBFA2T1,a Gene Rearranged in Human Leukemia, Is a Member of a Multigene Family

MTG8(HGMW-approved symbolCBFA2T1) was originally identified as one of the loci involved in the t(8;21)(q22;q22) of acute myeloid leukemia. We characterize two humanMTG8-related genes,MTGR1andMTGR2(HGMW-approved symbolsCBFA2T2andCBFA2T3). The former is duplicated in mouse, one locus possibly being a retroposon. MultipleMTG8-related sequences are found in several vertebrate species, from fish to mammals, albeit not in a urodele.MTGR2maps to 16q24 and, likeMTG8andMTGR1,is close to one of three loci encoding a syntrophin (dystrophin-associated proteins). Moreover, an alternativeMTGR1promoter/5′ exon is contained within the α1-syntrophin locus. Thus, the two classes of genes may define novel paralogous groups.MTGR1is expressed mainly in brain, whileMTGR2is expressed in the thymus and possibly in monocytes. LikeMTG8, MTGR1is transcribed into a number of isoforms due to alternative splicing of different 5′ exons onto a common splice acceptor site. Comparison of the three predicted human MTG8-related polypeptides to theirDrosophilacounterpart (nervy) highlights four separate regions of sequence conservation that may correspond to distinct domains. The most NH₂-terminal of these is proportionately more conserved among the human polypeptides, presumably due to specific structural/functional constraints.