Sequence analysis predicted that the 4,834-amino acid protein, which is 95% identical and 99% similar to the mouse protein, contains 3 RCC1-like domains (RLDs); a putative ZZ-type zinc finger motif with 6 conserved cysteines and 2 outlying histidine residues; a C-terminal HECT or E3 ubiquitin ligase domain; and several potential phosphorylation sites. The overall structure is similar to that of HERC1, although HERC1 has only 2 RLDs and no zinc finger motif. The C-terminal region of HERC2 resembles that of HERC3.

Northern blot analysis revealed ubiquitous expression of a 15.5-kb HERC2 transcript, with high levels in fetal tissues and adult skeletal muscle, heart, ovary, testis, and brain.