E3 ubiquitin-protein ligase KCMF1 (KCMF1)

E3 ubiquitin-protein ligase KCMF1 (KCMF1) is a zinc finger-containing E3 ligase that regulates protein ubiquitination, autophagy, and potentially potassium channel activity[1][2][3]. KCMF1 forms a functional E2–E3 complex with RAD6 and UBR4, mediating polyubiquitination and targeting damaged or oxidized proteins for lysosome-mediated degradation, especially under cellular stress[1][2][3]. The protein is implicated in multiple cancer types, often exhibiting dysregulated expression in tumors (e.g., upregulation in pancreatic cancer or as a prognostic biomarker in oral squamous cell carcinoma)[1][2][3]. KCMF1 may act as either a tumor suppressor or oncogene depending on context, and also contributes to kidney tubulogenesis and suppressing or promoting cell proliferation[1][3]. While not a channel itself, it influences potassium ion channel activity and cellular ionic homeostasis, especially in cancer environments. KCMF1 dysfunction is associated with abnormal autophagy, disrupted protein degradation, and alterations in tumor microenvironmental ion composition. There are no direct drug modulators currently established for KCMF1[2][3].

Other names

Potassium channel modulatory factor 1FIGCZZZ1PCMFDEBT91DKFZP434L1021FGF-induced in gastric cancerZZ-type zinc finger-containing protein 1FGF-induced ubiquitin-protein ligase in gastric cancersRING-type E3 ubiquitin transferase KCMF1zinc finger, ZZ domain containing 1

Targeted for therapeutic inhibition to restore protein homeostasis or autophagy (theoretical, not drug-validated); Indirect modulation by microRNAs impacting expression (e.g., miR-210, miR-346)