Ubiquitin-like protein

Ubiquitin-like proteins (UBLs) are a family of small proteins involved in post-translational modification of other proteins in a cell, usually with a regulatory function. The UBL protein family derives its name from the first member of the class to be discovered, ubiquitin (Ub), best known for its role in regulating protein degradation through covalent modification of other proteins. Following the discovery of ubiquitin, many additional evolutionarily related members of the group were described, involving parallel regulatory processes and similar chemistry. UBLs are involved in a widely varying array of cellular functions including autophagy, protein trafficking, inflammation and immune responses, transcription, DNA repair, RNA splicing, and cellular differentiation.

Discovery

Ubiquitin itself was first discovered in the 1970s and originally named "ubiquitous immunopoietic polypeptide". Subsequently, other proteins with sequence similarity to ubiquitin were occasionally reported in the literature, but the first shown to share the key feature of covalent protein modification was ISG15, discovered in 1987. A succession of reports in the mid 1990s is recognized as a turning point in the field, with the discovery of SUMO (small ubiquitin-like modifier, also known as Sentrin or SENP1) reported around the same time by a variety of investigators in 1996, NEDD8 in 1997, and Apg12 in 1998. A systematic survey has since identified over 10,000 distinct genes for ubiquitin or ubiquitin-like proteins represented in eukaryotic genomes.

Structure and classification

Members of the UBL family are small, non-enzymatic proteins that share a common structure exemplified by ubiquitin, which has 76 amino acid residues arranged into a "beta-grasp" protein fold consisting of a five-strand antiparallel beta sheet surrounding an alpha helix. The beta-grasp fold is widely distributed in other proteins of both eukaryotic and prokaryotic origin.