240-kDa proteasome inhibitor (CF-2) is identical to delta-aminolevulinic acid dehydratase.

The 240-kDa proteasome inhibitor has been reported to be an ATP-stabilized component (CF-2) of the 26 S proteasome complex. We now report that this inhibitory factor is indistinguishable from delta-aminolevulinic acid dehydratase (ALAD), the second enzyme in the pathway of heme synthesis, based upon the following observations: 1) common sequence of the first 14 N-terminal amino acids; 2) identical migration on native and SDS-polyacrylamide gel electrophoresis; 3) identical isoelectric points of pH 7.1; 4) cross-reactivity of specific polyclonal antibodies; 5) similar dehydratase and proteasome inhibitor specific activities in both proteins; and 6) the presence of both activities in recombinant ALAD. The dual role of this protein as CF-2 in the ATP/ubiquitin-dependent pathway and in heme synthesis may be an example of "gene sharing" and explains the unexpected abundance of ALAD noted in earlier studies.