Se. Schwarz et al., CHARACTERIZATION OF HUMAN HECT DOMAIN FAMILY MEMBERS AND THEIR INTERACTION WITH UBCH5 AND UBCH7, The Journal of biological chemistry, 273(20), 1998, pp. 12148-12154
The beet domain protein family was originally identified by sequence s
imilarity of its members to the C-terminal region of E6-AP, an E3 ubiq
uitin-protein ligase. Since the C terminus of E6-AP mediates thioester
complex formation with ubiquitin, a necessary intermediate step in E6
-AP-dependent ubiquitination, it was proposed that members of the beet
domain family in general have E3 activity. The beet domain is approxi
mately 350 amino acids in length, and we show here that the beet domai
n of E6-AP is necessary and sufficient for ubiquitin thioester adduct
formation. Furthermore, the human genome encodes at least 20 different
beet domain proteins, and in further support of the hypothesis that b
eet domain proteins represent a family of E3s, several of these are sh
own to form thioester complexes with ubiquitin. In addition, some beet
domain proteins interact preferentially with UbcH5, whereas others in
teract with UbcH7, indicating that human beet domain proteins can be g
rouped into at least two classes based on their E2 specificity. Since
E3s are thought to play a major role in substrate recognition, the pre
sence of a large family of E3s should contribute to ensure the specifi
city and selectivity of ubiquitin-dependent proteolytic pathways.