Ubiquitin/UBLs

Ubiquitin (Ub) is an evolutionarily conserved, heat-stable small protein containing 76 amino acids that is ubiquitously expressed in eukaryotic cells. It is highly conserved with little variance in animal species from insects to humans. Only 2-3 amino-acid residues vary between the yeast and plant and the yeast and human protein. Ubiquitin serves as a post-translational modifier of cellular substrates. Ubiquitin can be reversibly attached onto other proteins as a monomer or as a poly-ubiquitin chain of diverse structural topologies, and provides exceptionally flexible control over processes from cell division to cell death, from gene transcription to protein degradation, by dictating protein interaction, function, and turnover. Ubiquitin-like proteins (UBLs) encompass a family of proteins that share structural and evolutionary relationships with ubiquitin. The UBLs, including ubiquitin itself, share the same basic three-dimensional core structure, the β-grasp fold. Most UBLs are conjugated to proteins via an enzymatic cascade that resembles ubiquitylation, and many of their components are related to those involved in ubiquitylation. The UBLs family includes 10 members: small ubiquitin modifier (SUMO), neural precursor cell expressed developmentally downregulated 8 (NEDD8) or Related to Ubiquitin 1 (RUB 1) in yeast, Ubiquitin-Related Modifier-1 (URM1), Ubiquitin-fold Modifier 1 (UFM1), autophagy-related proteins 8 and 12 (ATG8 and ATG12), interferon-stimulated gene 15 (ISG15), human leukocyte antigen (HLA)-F adjacent transcript 10 (FAT10), fan ubiquitin-like protein 1 (FUB1), and histone mono-ubiquitination 1 (HUB1). Ubiquitin and UBLs are critical regulators of complex cellular processes such as the cell cycle, DNA repair, transcription, chromatin remodeling, signal translation, and protein degradation.