Recombinant Human Ub protein

**Background of UBR4 Recombinant Protein**

UBR4 (Ubiquitin Protein Ligase E3 Component N-Recognin 4) is a member of the N-end rule pathway, a conserved proteolytic system that targets specific proteins for degradation via the ubiquitin-proteasome system. As an E3 ubiquitin ligase, UBR4 plays a critical role in recognizing substrate proteins bearing destabilizing N-terminal residues, marking them for polyubiquitination and subsequent proteasomal breakdown. Beyond its canonical role in protein quality control, UBR4 is implicated in diverse cellular processes, including DNA repair, apoptosis, cell cycle regulation, and maintenance of genomic stability. Its large size (~600 kDa) and structural complexity, featuring multiple substrate-binding domains (e.g., UBA, RING), enable interactions with a wide array of partners, underscoring its functional versatility.

Recombinant UBR4 protein is engineered for in vitro studies to dissect its molecular mechanisms, substrate specificity, and regulatory networks. Produced using heterologous expression systems (e.g., mammalian cells, baculovirus), recombinant UBR4 retains enzymatic activity and structural integrity, enabling biochemical assays, structural analyses (e.g., cryo-EM), and screening for modulators. Research highlights its involvement in pathologies: UBR4 dysregulation is linked to cancer progression, neurodegenerative disorders (e.g., Alzheimer’s), and developmental defects. For instance, UBR4 interacts with amyloid precursor protein (APP), influencing Aβ plaque formation, and its loss promotes genomic instability in tumors.

Despite advances, challenges remain in understanding UBR4’s full interactome and context-dependent roles. Recombinant UBR4 tools are pivotal for unraveling these complexities, offering potential therapeutic avenues for diseases tied to proteostasis imbalance.

Ubiquitin (Ub), a highly conserved 76-amino-acid protein found in eukaryotes, plays a central role in regulating cellular protein homeostasis. Discovered in 1975. Ub is best known for its ability to tag proteins for degradation via the ubiquitin-proteasome system (UPS). This post-translational modification, termed ubiquitination, involves a cascade of E1 (activating), E2 (conjugating), and E3 (ligating) enzymes that attach Ub to lysine residues on substrate proteins. Polyubiquitin chains typically serve as recognition signals for the 26S proteasome, directing marked proteins for proteolytic breakdown. Beyond degradation, Ub modifications also regulate diverse processes like DNA repair, immune signaling, and endocytosis, depending on chain topology and target sites.

Recombinant Ub proteins, produced through genetic engineering in bacterial (e.g., E. coli) or eukaryotic expression systems, retain native structure and functional properties. Their standardized production enables broad applications: studying UPS mechanisms, developing therapeutics targeting Ub-related pathways (e.g., cancer proteasome inhibitors), and serving as tools in structural biology. Modified variants—including mutant forms, fluorescent tags, or activity-based probes—have expanded research capabilities. For example, non-hydrolyzable Ub chains help dissect deubiquitinase functions, while tagged Ub aids in live-cell imaging. Recent advances in cryo-EM and mass spectrometry have further driven demand for high-purity recombinant Ub to investigate dynamic Ub-protein interactions at atomic resolution. As a cornerstone of cellular regulation, Ub continues to be a critical focus in both basic research and drug discovery.