This domain has a high identity with that of other human E3 ubiquitin ligases such as RNF128,18 RNF130,19 and mouse Rnf133.20In vitro ubiquitination reaction has shown that the recombinant RNF148 protein has E3 ubiquitin ligase activity.21 Now we found for the first time that RNF148 may have an important role in human gastric and colorectal cancer development through its E3 ubiquitin ligase function though more detailed molecular mechanisms of its ubiquitin-proteasome regulation of CHAC2 expression will be studied further. The gene discussed is RNF133; the disease is colorectal cancer.