Makorin ring finger protein 1 (MKRN1)

Makorin ring finger protein 1 (MKRN1) is an E3 ubiquitin ligase characterized by a RING finger motif and multiple C3H-type zinc finger domains, conferring both ubiquitin ligase activity and RNA-binding capacity. MKRN1 catalyzes the transfer of ubiquitin to target proteins, marking them for proteasomal degradation or modulating their function, localization, or turnover. Key substrates include proteins involved in cell cycle control (p53, p21), apoptosis (FADD), metabolism (AMPK, PTEN), and viral defense. MKRN1 also directly binds to RNA, influencing mRNA stability, translation, and responses to cellular stress. Its dysregulation is implicated in metabolic diseases (by controlling energy sensors like AMPK), various cancers (via tumor suppressor degradation), cardiovascular disease, and viral pathogenesis. As such, MKRN1 is both mechanistically and therapeutically relevant, though it remains without approved drugs targeting it directly.

Other names

E3 ubiquitin-protein ligase makorin-1RNF61RING finger protein 61RING-type E3 ubiquitin transferase makorin-1

MKRN1 functions as an E3 ubiquitin ligase, mediating ubiquitination and subsequent proteasomal degradation of various substrates, including AMPK, p53, p21, PTEN, APC, FADD, and select viral proteins. This includes the ubiquitylation of AMPKα, which influences energy metabolism and insulin signaling.