Ubiquitin-like modifier-activating enzyme 5 (UBA5)

Ubiquitin-like modifier-activating enzyme 5 (UBA5) is an E1-like enzyme responsible for activating UFM1 (ubiquitin-fold modifier 1), a ubiquitin-like protein, via initial adenylation of UFM1's C-terminal glycine with ATP and subsequent formation of a thioester bond with its catalytic cysteine (Cys250) within the enzyme's adenylation domain[1][2][5]. UBA5 thus catalyzes the first step in the ufmylation cascade, analogous to ubiquitylation, forming a UBA5~UFM1 thioester intermediate, which subsequently enables transfer of UFM1 to the E2 enzyme UFC1 and, ultimately, conjugation to target proteins[2][3][4]. UBA5 is unique among E1 enzymes for its structural simplicity and the distinctive location of its catalytic cysteine, and its activity is essential for normal development and neurological function, as evidenced by disease-causing mutations in humans[5]. There are currently no approved drugs known to interact directly with UBA5.

Other names

UBE1DC1FLJ23251ThiFP1UFM1-activating enzymeUbiquitin-activating enzyme E1 domain-containing protein 1DEE44EIEE44SCAR24THIFP1Ubiquitin-activating enzyme E1 homolog (yeast)

No clinically established drugs currently target UBA5 directly. Mechanistically, inhibition or modulation would in principle disrupt ufmylation by preventing activation of UFM1 and downstream signaling.