Multiple Forms of the Menkes Cu-ATPase

The 5′ region of MNK cDNAs has a 45 bp insert terminating at the 5′end with an AGATG sequence. The ATG in the sequence is in-frame with the ATG downstream identified by Vulpe et al (1993) as a translation start site for MNK mRNA. Inserts of 192 bp and 45 bp have been found in the 5′ region of MNK mRNAs from BeWo cells, Caco-2 cells and normal human fibroblasts. Extensions to the 5′ end of these mRNAs could foretell a modified N-ter-mini in certain forms of the Menkes Cu-ATPase These modified H2N-terminal extensions are postulated to be targeting signals for post-translational processing and cellular localization. In this report, we provide evidence that the primary Menkes transcript in non-Menkes cells undergoes post-transcriptional splicing that gives rise to multiple transcripts. The data suggest that the Menkes gene is a copper locus that codes for more than one form of the Menkes Cu-ATPase and one of these forms could be a small Cu transport protein.