UBA3 Activators

Common UBA3 Activators include, but are not limited to Spermidine CAS 124-20-9, Kinetin CAS 525-79-1, Trichostatin A CAS 58880-19-6, Rapamycin CAS 53123-88-9 and MG-132 [Z-Leu- Leu-Leu-CHO] CAS 133407-82-6.

UBA3 (Ubiquitin-like modifier-activating enzyme 3) is a crucial enzyme in the ubiquitin-like protein (UBL) conjugation pathway, specifically involved in the activation of NEDD8, a ubiquitin-like molecule. This enzyme forms a part of the NEDD8-activating enzyme (NAE) complex, which is essential for the neddylation process-a post-translational modification where NEDD8 is covalently attached to target proteins. Neddylation, akin to ubiquitination, alters the function, localization, or stability of substrate proteins and is pivotal for regulating various cellular processes, including cell cycle progression, signal transduction, and responses to stress. UBA3 plays a fundamental role in this pathway by catalyzing the first step in the neddylation cycle: the ATP-dependent activation of NEDD8. This activation is critical for the conjugation of NEDD8 to its substrates, a process that requires precise enzymatic coordination to ensure the transfer of NEDD8 from UBA3 to its target proteins through a cascade of enzymatic reactions involving E1, E2, and E3 enzymes, similar to the ubiquitination pathway.

The activation mechanism of UBA3 involves the formation of a heterodimer with UBA1 (also known as NAE1), which together bind ATP and NEDD8, facilitating the adenylation of the C-terminal glycine of NEDD8. This adenylation is a critical activation step, enabling the subsequent transfer of NEDD8 to the catalytic cysteine of UBA3 in an ATP-dependent manner. The formation of this thioester bond between NEDD8 and UBA3 is a key regulatory point in the neddylation pathway, determining the specificity and efficiency of NEDD8 transfer to downstream E2 enzymes and, ultimately, to substrate proteins. The intricate regulation of UBA3's activity is further modulated by the interaction with other cellular proteins and post-translational modifications, which can affect its stability, localization, and interaction with NEDD8 and E2 enzymes. These regulatory mechanisms ensure that neddylation is tightly controlled in response to cellular needs, allowing UBA3 to modulate various biological processes by influencing the function and degradation of key regulatory proteins. Through its central role in the neddylation pathway, UBA3 orchestrates the dynamic modulation of protein function, playing a vital role in maintaining cellular homeostasis and responding to cellular signals and stress conditions.