STRUCTURE AND ORGANIZATION OF THE HUMAN METAXIN GENE (MTX) AND PSEUDOGENE

Metaxin encodes a mitochondrial protein and is an essential nuclear ge ne in mice. The cDNA sequence and genomic organization of the human me taxin gene (MIX) have now been determined, MIX is 6 kb and consists of eight protein-encoding exons, The gene is contiguous to thrombospondi n 3 (THBS3) and to the pseudogene for glucocerebrosidase (psGBA), but is transcribed in a direction opposite to the latter two genes. Thus, MIX and THBS3 share a common promoter region and are transcribed diver gently, whereas MIX and psGBA are transcribed convergently and have cl osely apposed polyadenylation sites, Human metaxin contains 317 amino acids and is 91.5% identical to mouse metaxin. Metaxin is rich in leuc ine (14.2%) and in basic (12.9%) and acidic (12.0%) amino acids, The p redicted protein lacks an amino-terminal signal sequence and N-glycosy lation sites, but contains a putative transmembrane domain near its ca rboxy terminus, A DNA duplication has led to a direct repeat and the e volution of a pseudogene for GBA. A pseudogene for metaxin (psMTX) is also located within the 16 kb of DNA separating GBA from psGBA. The ps MTX 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 hig hly 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 MIX and at least in liver, the pseudogene is n ot expressed. (C) 1996 Academic Press, Inc.