HERC2 Protein, Human (His)

HERC2 Protein, functioning as an E3 ubiquitin-protein ligase, plays a crucial role in the regulation of ubiquitin-dependent retention of repair proteins on damaged chromosomes, particularly in response to ionizing radiation (IR). Upon recruitment to sites of DNA damage, HERC2 facilitates the assembly of UBE2N and RNF8, promoting the formation of 'Lys-63'-linked ubiquitin chains crucial for DNA damage-induced responses. Acting as a mediator between UBE2N and RNF8, it ensures binding specificity, while also contributing to the maintenance of RNF168 levels. Moreover, HERC2 serves as an E3 ligase that orchestrates the ubiquitination and subsequent proteasomal degradation of XPA, impacting the circadian oscillation of DNA excision repair activity. Beyond its role in DNA repair, HERC2 indirectly regulates the insulin-like growth factor receptor signaling pathway by controlling the steady-state expression of the IGF1R receptor. Additionally, HERC2 plays a role in iron metabolism by modulating the basal turnover of FBXL5. This multifaceted functionality highlights the importance of HERC2 in coordinating various cellular processes essential for genomic stability and signaling regulation.