UBA5 Protein, Human (His)

UBA5, functioning as an E1-like enzyme, plays a pivotal role in the initiation of ufmylation, a post-translational modification process. The activation of UFM1 begins with the adenylation of its C-terminal glycine residue by UBA5 in conjunction with ATP. This results in the formation of a UFM1-E1 thioester and free AMP. Notably, UBA5 achieves this through a trans-binding mechanism, where UFM1 interacts with distinct sites in both subunits of the UBA5 homodimer. This trans-binding not only facilitates the stabilization of the UBA5 homodimer but also enhances ATP-binding. Subsequently, UFM1 is transferred from UBA5 to the E2-like enzyme UFC1, again employing a trans mechanism. Ufmylation, orchestrated by UBA5, emerges as a critical process involved in reticulophagy (ER-phagy) triggered by endoplasmic reticulum stress. Moreover, Ufmylation proves indispensable for the erythroid differentiation of both megakaryocytes and erythrocytes. UBA5 exists as a homodimer, and this homodimerization is essential for UFM1 activation. UBA5 also engages in specific interactions with UFM1, GABARAPL2, GABARAP, GABARAPL1, and UFC1, underscoring its intricate involvement in diverse cellular processes.