TRIADs: A new class of proteins with a novel cysteine-rich signature

Triad1 was recently identified as a nuclear RING finger protein, which is u p-regulated during retinoic acid induced granulocytic differentiation of ac ute leukemia cells. Here we show that a cysteine-rich domain (C6HC), presen t in Triad1, is conserved in at least 24 proteins encoded by various eukary otes. The C6HC consensus pattern C-x(4)C-x(14-30)-C-x(1-4)-C-x(4)-C-x(2)-C- x(4)-H-x(4)-C defines this structure as the fourth family member of the zin c-binding RING, LIM, and LAP/PHD fingers. Strikingly, in 22 of 24 proteins the C6HC domain is flanked by two RING finger structures. We have termed th e novel C6HC motif DRIL (double RING finger linked). The strong conservatio n of the larger tripartite TRIAD (two RING fingers and DRIL) structure indi cates that the three subdomains are functionally linked and identifies a no vel class of proteins.