E3 ubiquitin-protein ligase MYCBP2 (MYCBP2)

E3 ubiquitin-protein ligase MYCBP2 (abbreviated as MYCBP2 and also known as PAM, PHR1, and Highwire) is a large, multifunctional enzyme and signaling hub involved in fundamental cellular processes including neural development, synaptic growth, axon guidance, and cell cycle regulation[1][3][6]. As an atypical RING-type E3 ubiquitin ligase, MYCBP2 mediates proteasomal degradation of proteins primarily through ubiquitination of threonine and serine rather than classical lysine residues, utilizing a distinct RING–Cys–relay mechanism[3][6]. MYCBP2 directly regulates cAMP and mTOR signaling, autophagy, and interacts with key pathways in neural and cancer biology. Loss or mutation of MYCBP2 disrupts neuronal connectivity and axon stability; altered expression is linked to human diseases such as certain leukemia subtypes, neurodevelopmental defects, and cancer. In the nervous system, MYCBP2 works in complexes with proteins like FBXO45 and EPH receptors to integrate signals and regulate receptor turnover and cellular responses[1][3]. Despite its clear roles in disease, there are currently no drugs specifically approved or widely reported to target MYCBP2 directly.

Other names

MYC binding protein 2PAMKIAA0916PHR1Protein associated with MycMyc-bp2PAM/Highwire/RPM-1 protein 1HighwireFLJ10106RING-type E3 ubiquitin transferase MYCBP2

Inhibition or modulation of E3 ubiquitin-protein ligase activity; Disruption of MYCBP2-coupled signaling complexes