ubiquitininteracting

Ubiquitin-interacting refers to the ability of proteins to bind ubiquitin or polyubiquitin chains, enabling a range of cellular processes. Many ubiquitin-interacting proteins do not modify ubiquitin themselves but recognize ubiquitin signals to regulate localization, activity, or turnover.

Mechanisms and domains: The interaction is usually mediated by ubiquitin-binding domains (UBDs) such as ubiquitin-associated (UBA) domains, ubiquitin-interacting motifs (UIMs), ubiquitin-binding zinc finger (UBZ) domains, NZF (Npl4-type zinc finger) domains, and CUE domains. Some proteins contain multiple UBDs, providing higher affinity or specificity for certain chain linkages (e.g., K48-linked or K63-linked chains). Ubiquitin recognition can distinguish mono-ubiquitination from polyubiquitination and may favor particular linkage types or chain lengths, influencing downstream outcomes.

Functional roles: Recognition of ubiquitin signals can recruit substrates to proteasomes, assemblies, or membranes, or regulate DNA repair, signaling pathways, endocytosis, and autophagy. Shuttle factors such as Rad23 and Dsk2 in yeast carry ubiquitinated clients to the proteasome via their UBA domains, linking recognition to degradation. Other ubiquitin-interacting proteins participate in signaling complexes, trafficking, or chromatin regulation by interpreting ubiquitin marks.

Biological significance: Proper ubiquitin-interacting function is essential for protein quality control and cellular homeostasis. Dysregulation is associated with neurodegenerative diseases and cancer. Research in this field maps ubiquitin-binding domains, clarifies chain-type preferences, and explores modulators that affect ubiquitin interactions as potential therapeutic strategies.