Fig. 1

The functional domains of HUWE1 and functional enrichment of HUWE1. a Schematic diagram of the structural features of HUWE1 protein. Huwe1 protein mainly contains four domains: 1) the UBA domain and 2) the WWE domain, 3) the BH3 domain, and 4) the HECT domain. The HECT domain contains a catalytic cysteine residue for the ubiquitin-thioester bond formation and therefore carries the enzymatic activity of HUWE1 protein. Crystal structural analysis shows that the activity of HUWE1 can be self-activated through an activation segment. HUWE1 proteins exhibit the dimerization ability using the region close to the N-terminus of the HECT domain. b Functional enrichment of HUWE1. Based on the substrates regulated by HUWE1, HUWE1 is involved in four major aspects of cellular regulation: Proliferation/differentiation, apoptosis, DNA repair, and stress response. Dysregulation of HUWE1, either through the impaired enzymatic activity or the aberrant expression of HUWE1, leads to disease development, such as tumor formation