UBA domain found in vertebrate ubiquitin-conjugating enzyme E2 K (UBE2K), Drosophila melanogaster ubiquitin-conjugating enzyme E2-22 kDa (UbcD4) and similar proteins
UBE2K, also called Huntingtin-interacting protein 2 (HIP-2), ubiquitin carrier protein, ubiquitin-conjugating enzyme E2-25 kDa (E2-25K), or ubiquitin-protein ligase, is a multi-ubiquitinating enzyme with the ability to synthesize Lys48-linked polyubiquitin chains which is involved in the ubiquitin (Ub)-dependent proteolytic pathway. It interacts with the frameshift mutant of ubiquitin B and functions as a crucial factor regulating amyloid-beta neurotoxicity. It has also been characterized as Huntingtin-interacting protein that modulates the neurotoxicity of Amyloid-beta (Abeta), the principal protein involved in Alzheimer's disease pathogenesis. Moreover, E2-25K increases aggregate the formation of expanded polyglutamine proteins and polyglutamine-induced cell death in the pathology of polyglutamine diseases. UbcD4, also called ubiquitin carrier protein, or ubiquitin-protein ligase, is encoded by Drosophila E2 gene which is only expressed in pole cells in embryos. It is a putative E2 enzyme homologous to the Huntingtin interacting protein-2 (HIP2) of human. UbcD4 specifically interacts with the polyubiquitin-binding subunit of the proteasome. This family also includes a putative ubiquitin conjugating enzyme from plasmodium Yoelii (pyUCE). It shows a high level of sequence similarity with UBE2K and may also plays a role in the ubiquitin-mediated protein degradation pathway. All family members are class II E2 conjugating enzymes which contain a C-terminal ubiquitin-associated (UBA) domain in addition to an N-terminal catalytic ubiquitin-conjugating enzyme E2 (UBCc) domain.