E3 ubiquitin-protein ligase MIB1 (MIB1)

E3 ubiquitin-protein ligase MIB1 (MIB1) is a multi-domain enzyme containing ankyrin repeats, multiple RING finger domains, and zinc finger motifs, functioning as a RING-type E3 ubiquitin ligase[3][5]. It catalyzes the transfer of ubiquitin to specific substrate proteins, marking them for proteasomal degradation. MIB1 is a key positive regulator of Notch signaling, enabling the endocytosis and activation of Notch ligands (Delta/Jagged), which is crucial for cell-cell communication and differentiation in development[3][1][8]. Beyond Notch, MIB1 targets other substrates involved in diverse pathways, including Wnt/β-catenin signaling (via RYK), apoptosis (via DAPK1, cFLIP), the regulation of centriolar proteins (Plk4, PCM1), and the turnover of the survival of motor neuron (SMN) protein, implicating it in neurodegenerative disease[2][8][6]. Disruption or mutation of MIB1 has been linked to diseases such as cancer, cardiomyopathy (especially left ventricular noncompaction), and spinal muscular atrophy modifier phenotypes[3]. Due to its central role in development and homeostasis, therapeutic targeting of MIB1 must consider potential widespread effects[8][2].

Other names

DIP1KIAA1323ZZANK2ZZZ6DAPK-interacting protein 1Mind bomb homolog 1RING-type E3 ubiquitin transferase MIB1Zinc finger ZZ type with ankyrin repeat domain protein 2mindbomb E3 ubiquitin protein ligase 1ubiquitin ligase mind bomb

Protein ubiquitination and targeting for proteasomal degradation. Activation of Notch receptor pathway via ubiquitination of Notch ligands (Delta/Jagged). Modulation of Wnt/β-catenin pathway via receptor ubiquitination (e.g., RYK).