MYCBP2

Description

The MYCBP2 (MYC binding protein 2) is a protein-coding gene located on chromosome 13.

MYCBP2, also known as myc-binding protein 2 or protein associates with myc (PAM), is an enzyme that in humans is encoded by the MYCBP2 gene. PAM contains a N-terminal leucine zipper, central MYC-binding, and C-terminal histone-binding protein homology domains. MYCBP2 has been shown to interact with Myc.

MYCBP2 is an atypical E3 ubiquitin-protein ligase that specifically targets threonine and serine residues on proteins for ubiquitination, instead of the more common lysine residues. It exhibits esterification activity towards both threonine and serine, with a preference for threonine, and relies on two catalytic cysteine residues to transfer ubiquitin to its substrates via thioester intermediates. MYCBP2 interacts with E2 enzymes such as UBE2D1, UBE2D3, UBE2E1, and UBE2L3. This protein plays a crucial role in neural development, likely by mediating ubiquitination of threonine residues on target proteins. It is involved in various processes, including regulation of neurite outgrowth, synaptic growth, synaptogenesis, and axon degeneration. MYCBP2 is essential for the formation of major central nervous system axon tracts and proper axon growth by regulating axon navigation and branching through the regulation of MAP3K12/DLK subcellular location and stability. It also plays a role in proper localization of retinogeniculate projections, axon guidance in the olfactory system, and Wallerian axon degeneration. MYCBP2 catalyzes ubiquitination of threonine and/or serine residues on NMNAT2, although the consequences of this modification are not fully understood. It regulates the internalization of TRPV1 in peripheral sensory neurons and mediates ubiquitination and subsequent proteasomal degradation of TSC2/tuberin. Beyond its E3 ubiquitin-protein ligase activity, MYCBP2 functions as a guanosine exchange factor (GEF) for RAN in neurons of dorsal root ganglia. It might also facilitate or regulate transcriptional activation by MYC. MYCBP2 collaborates with HUWE1 to regulate circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1. {ECO:0000250|UniProtKB:Q7TPH6, ECO:0000269|PubMed:18308511, ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:26304119, ECO:0000269|PubMed:27278822, ECO:0000269|PubMed:29643511, ECO:0000269|PubMed:9689053}

MYCBP2 is also known as Myc-bp2, PAM, PHR1, Phr.

Associated Diseases

WES Whole Exome Sequencing