MYCBP2
GeneName
MYCBP2
Summary
MYCBP2, also known as PAM or Phr1, is a 514 kDa protein that is expressed in various cellular compartments including the nucleus, cytoplasm, axon, and plasma membrane. It functions primarily as a guanyl-nucleotide exchange factor and ubiquitin protein ligase, playing a role in the regulation of small GTPases and protein ubiquitination. MYCBP2 is involved in critical biological processes such as axon guidance, neuromuscular processes, and the regulation of cytoskeleton organisation, contributing to the proper localisation and assembly of proteins at synapses.
Importance
MYCBP2 is relevant to: - Neuronal development and function, particularly in axon guidance and synaptic assembly, which are essential for proper neural connectivity - Circadian regulation of gene expression, impacting various physiological processes - The regulation of protein ubiquitination, which is crucial for maintaining protein homeostasis and cellular functions - Potential implications in neurodegenerative diseases where axon guidance and synaptic integrity are disrupted
Top Products
For researchers investigating MYCBP2, we recommend the well-cited polyclonal antibody, Anti-MYCBP2 antibody (ab86078). This antibody has garnered 15 citations, reflecting its reliability and trust within the research community. It is particularly effective for Western blotting (WB), making it an excellent choice for those looking to study MYCBP2 in detail.
Abcam Product Citation Summary
The MYCBP2 target has been investigated in various contexts, particularly in relation to Wallerian degeneration and colon cancer. The use of Western blot analysis highlights its relevance in understanding protein expression in both mouse models and human cancer cell lines.
Abcam Product Citation Table
Domain
The PHR domains are compact beta-sandwich folds composed of 11 antiparallel strands and decorated with conserved apical loops. They are likely to play a structural role and mediate interactions with substrates or partners (By similarity).
The tandem cysteine domain region confers threonine specificity and contains the two essential catalytic cysteine residues that relay ubiquitin. It binds four zinc ions in a C5HC7HC2 configuration.
Function
Atypical E3 ubiquitin-protein ligase which specifically mediates ubiquitination of threonine and serine residues on target proteins, instead of ubiquitinating lysine residues (PubMed:29643511). Shows esterification activity towards both threonine and serine, with a preference for threonine, and acts via two essential catalytic cysteine residues that relay ubiquitin to its substrate via thioester intermediates (PubMed:29643511). Interacts with the E2 enzymes UBE2D1, UBE2D3, UBE2E1 and UBE2L3 (PubMed:18308511, PubMed:29643511). Plays a key role in neural development, probably by mediating ubiquitination of threonine residues on target proteins (Probable). Involved in different processes such as regulation of neurite outgrowth, synaptic growth, synaptogenesis and axon degeneration (By similarity). Required for the formation of major central nervous system axon tracts (By similarity). Required for proper axon growth by regulating axon navigation and axon branching: acts by regulating the subcellular location and stability of MAP3K12/DLK (By similarity). Required for proper localization of retinogeniculate projections but not for eye-specific segregation (By similarity). Regulates axon guidance in the olfactory system (By similarity). Involved in Wallerian axon degeneration, an evolutionarily conserved process that drives the loss of damaged axons: acts by promoting destabilization of NMNAT2, probably via ubiquitination of NMNAT2 (By similarity). Catalyzes ubiquitination of threonine and/or serine residues on NMNAT2, consequences of threonine and/or serine ubiquitination are however unknown (PubMed:29643511). Regulates the internalization of TRPV1 in peripheral sensory neurons (By similarity). Mediates ubiquitination and subsequent proteasomal degradation of TSC2/tuberin (PubMed:18308511, PubMed:27278822). Independently of the E3 ubiquitin-protein ligase activity, also acts as a guanosine exchange factor (GEF) for RAN in neurons of dorsal root ganglia (PubMed:26304119). May function as a facilitator or regulator of transcriptional activation by MYC (PubMed:9689053). Acts in concert with HUWE1 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (PubMed:20534529).
Pathway
Protein modification; protein ubiquitination.
Post-translational modifications
Autoubiquitinated.
Sequence Similarities
Belongs to the RING-Cys relay (RCR) family.
Tissue Specificity
Expressed in all tissues examined, expression is exceptionally abundant in brain and thymus. Colocalizes with TSC1 and TSC2 along the neurites and in the growth cones. Highly expressed in peripheral and central neurons. Colocalized with TSC1 in one of the filopodial extensions at the tip of a growth cone.
Cellular localization
- Nucleus
- Cell projection
- Axon
- Cytoplasm
- Cytoskeleton
- Localizes to axon shafts and associates with microtubule cytoskeleton (By similarity). Translocates to the nucleus following interaction with sumoylated RANGAP1 (PubMed:26304119).
Alternative names
KIAA0916, PAM, MYCBP2, E3 ubiquitin-protein ligase MYCBP2, Myc-binding protein 2, Protein associated with Myc