Structure and organization of the human metaxin gene (MTX) and pseudogene

Metaxin encodes a mitochondrial protein and is an essential nuclear gene in mice. The cDNA sequence and genomic organization of the human metaxin gene (MTX) have now been determined. MTX is 6 kb and consists of eight protein- encoding exons. The gene is contiguous to thrombospondin 3 (THBS3) and to the pseudogene for glucocerebrosidase (psGBA), but is transcribed in a direction opposite to the latter two genes. Thus, MTX and THBS3 share a common promoter region and are transcribed divergently, whereas MTX and psGBA are transcribed convergently and have closely apposed polyadenylation sites. Human metaxin contains 317 amino acids and is 91.5% identical to mouse metaxin. Metaxin is rich in leucine (14.2%) and in basic (12.9%) and acidic (12.0%) amino acids. The predicted protein lacks an amino-terminal signal sequence and N- glycosylation sites, but contains a putative transmembrane domain near its carboxy terminus. A DNA duplication has led to a direct repeat and the evolution of a pseudogene for GBA. A pseudogene for metaxin (psMTX) is also located within the 16 kb of DNA separating GBA from psGBA. The psMTX sequence is nearly identical to the 3' part of exon 2 through exon 8 of MTX, and both the intronic and the 3'-flanking sequences are highly conserved. Thus, there is a 278 amino acid open reading frame that is 97.8% identical to metaxin. However, psMTX lacks the first intron and promoter present in MTX, and at least in liver, the pseudogene is not expressed.