Ubiquitination factor E4A (UBE4A)

Ubiquitination factor E4A (UBE4A) is a member of the U-box family of enzymes that functions as both an E3 and E4 ubiquitin ligase, facilitating multiubiquitin chain assembly[2][4]. UBE4A plays a critical role in the DNA damage response, particularly in the repair of double-strand breaks (DSBs) by regulating the length of ubiquitin chains at sites of DNA damage[1]. It acts downstream of canonical E3 ligases and 53BP1, enabling precise control over protein ubiquitylation, ensuring balanced pathway choice between homologous recombination and alternative end-joining in DSB repair[1]. UBE4A is also involved in regulating chromosome condensation and separation through the polyubiquitination of securin[2]. Genetic disruption or deficiency in UBE4A leads to defects in DNA repair, contributing to neurodevelopmental disorders and possibly tumorigenesis. Autoantibodies against UBE4A have been observed in autoimmune diseases such as scleroderma and Crohn's disease[2]. UBE4A is evolutionarily conserved and operates in concert with other ubiquitin-proteasome pathway components, but as of now, there are no approved drugs targeting UBE4A directly.

Other names

Ubiquitin conjugation factor E4 AKIAA0126UBOX2UFD2E4RING-type E3 ubiquitin transferase E4ANEDHMS

Ubiquitin chain extension via E4 ligase activity, Lys48-linked polyubiquitination of substrates, Regulation of DNA repair pathway choice