IDENTIFICATION OF A SET OF YEAST GENES-CODING FOR A NOVEL FAMILY OF PUTATIVE ATPASES WITH HIGH SIMILARITY TO CONSTITUENTS OF THE 26S PROTEASE COMPLEX

There is accumulating evidence for a large, highly conserved gene fami ly of putative ATPases. We have identified 12 different members of thi s novel gene family (the YTA family) in yeast and determined the nucle otide sequences of nine of these genes. All of the putative gene produ cts are characterized by the presence of a highly conserved domain of 300 amino acids containing specialized forms of the A and B boxes of A TPases. YTA1, YTA2, YTA3 and YTA5 exhibit significant similarity to pr oteins involved in human immunodeficiency virus Tat-mediated gene expr ession but more significantly to subunits of the human 26S proteasome. YTA1 and YTA2 are essential genes in yeast. Remarkably, the cDNA of h uman TBP-1 can compensate for the loss of YTA1. Preliminary experiment s indicate that YTA1 is a component of the 26S protease complex from y east. Our findings lead us to propose that YTA1, YTA2, YTA3 and YTA5 f unction as regulatory subunits of the yeast 26S proteasome. YTA10, YTA 11 and YTA12 share significant homology with the Escherchia coli FtsH protein, and together with YTA4 and YTA6 may constitute a separate sub class within this family of putative ATPases.