CUE Domain Containing 1 Human Recombinant
CUE Domain Containing 2 Human Recombinant
CUE domain-containing proteins are characterized by the presence of a CUE domain, a ubiquitin-binding motif approximately 40 amino acids in length . The CUE domain was first identified in yeast Cue1 and human Tollip proteins . These domains are structurally related to the ubiquitin-associated (UBA) domain and are involved in various cellular processes, including protein degradation and sorting .
Key Biological Properties: CUE domains bind both mono- and polyubiquitin, and some CUE domain-containing proteins are ubiquitinated in a CUE domain-dependent manner . The domain is composed of a three-helix bundle with conserved motifs that interact with ubiquitin .
Expression Patterns and Tissue Distribution: CUE domain-containing proteins are expressed in various tissues and are involved in multiple cellular functions. For example, CUEDC2 is highly expressed in many types of tumors and plays a role in cell cycle regulation, inflammation, and tumorigenesis .
Primary Biological Functions: CUE domain-containing proteins are involved in the degradation of misfolded proteins in the endoplasmic reticulum and protein sorting . They also play roles in immune responses and pathogen recognition by interacting with ubiquitin and other signaling molecules .
Role in Immune Responses and Pathogen Recognition: These proteins are implicated in the regulation of immune responses through their interactions with ubiquitin and other immune signaling pathways .
Mechanisms with Other Molecules and Cells: CUE domains interact with ubiquitin through conserved motifs, forming domain-swapped dimers that enhance their binding affinity . These interactions facilitate the degradation of misfolded proteins and the regulation of various signaling pathways .
Binding Partners and Downstream Signaling Cascades: CUE domain-containing proteins bind to mono- and polyubiquitin, and their binding partners include proteins like Vps9, Cue1, and Tollip . These interactions trigger downstream signaling cascades involved in protein degradation and immune responses .
Regulatory Mechanisms Controlling Expression and Activity: The expression and activity of CUE domain-containing proteins are regulated at multiple levels, including transcriptional regulation and post-translational modifications .
Transcriptional Regulation and Post-Translational Modifications: CUEDC2, for example, is phosphorylated by Cdk1 during mitosis, promoting the release of the anaphase-promoting complex or cyclosome (APC/C) from checkpoint inhibition . It also interacts with IκB kinase α (IKKα) and IKKβ, inhibiting the activation of nuclear factor-κB .
Biomedical Research: CUE domain-containing proteins are valuable in biomedical research for understanding protein degradation pathways and immune responses .
Diagnostic Tools and Therapeutic Strategies: These proteins have potential applications in diagnostic tools and therapeutic strategies, particularly in cancer research. For instance, CUEDC2’s role in regulating hormone receptors makes it a target for breast cancer therapies .
Role Throughout the Life Cycle: CUE domain-containing proteins play critical roles throughout the life cycle, from development to aging and disease. They are involved in cell cycle regulation, inflammation, and tumorigenesis . Their functions in protein degradation and immune responses are essential for maintaining cellular homeostasis and responding to environmental stressors .