UBA1

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UBA1 (ubiquitin-like modifier activating enzyme 1) is a human enzyme that starts the process of tagging proteins with ubiquitin, a small protein that marks proteins for destruction or changes how they behave in the cell. It activates ubiquitin using ATP, forms a temporary bond, and then passes ubiquitin to the next enzyme in the tagging chain. UBA1 also helps regulate the related NEDD8 pathway, which is involved in protein folding and stress responses.

UBA1 is the main ubiquitin-activating enzyme in humans, with UBA6 as the other family member. Because ubiquitination controls many cell activities, UBA1 participates in essential processes such as the cell cycle, endocytosis, signaling, apoptosis, DNA repair, and gene regulation. Mutations in UBA1 are linked to X‑linked spinal muscular atrophy type 2, and the gene has also been associated with certain neurodegenerative diseases and cancers. A somatic mutation at methionine 41 in UBA1 causes VEXAS syndrome, an autoinflammatory condition.

Researchers are exploring UBA1 inhibitors as cancer therapies. Compounds like largazole (and its derivatives) block the first step of ubiquitin attachment, while others target the NEDD8 pathway (e.g., MLN4924). Early studies show potential for cancer treatment, but because UBA1 is important for normal cells, safety is carefully considered. The UBA1 gene is located on the X chromosome in humans.