Ubiquitin has a distinct and functionally important hydrophobic patch whose surface is defined by three residues including Leu⁸, Ile⁴⁴ and Val⁷⁰. These residues are solvent accessible in ubiquitin chains and are critical for poly-ubiquitin chain interaction and recognition by the 26S proteasome and subsequent target degradation. These hydrophobic residues interact directly with various factors that bind to Ub and/or mediate Ub-Ub interactions in ubiquitin chains that may influence orientation and recognition. Ubiquitin V70A can form an E1-catalyzed active thioester at the
C-terminus allowing the molecule to be transferred to the lysines of substrate proteins.