The ubiquitin-conjugating enzyme UbcM4 was previously shown to be necessary for normal mouse development. As a first step in identifying target proteins or proteins involved in the specificity of UbcM4-mediated ubiquitylation, we have isolated seven cDNAs encoding proteins that specifically interact with UbcM4 but with none of the other Ubcs tested. This interaction was observed in yeast as well as in mammalian cells. With one exception, all UbcM4-interacting proteins (UIPs) belong to a family of proteins that contain a RING finger motif. As they are structurally related to RING finger proteins that have recently been shown to play an essential role in protein ubiquitylation and degradation, the possibility is discussed that UIPs are involved in the specific recognition of substrate proteins of UbcM4.