The ubiquitin-associated (UBA) domain is an approximately 40 amino acid motif that was first recognized in proteins associated with ubiquitination but is also found in proteins involved in DNA nucleotide excision-repair and other proteins (1). UBA domains have been shown to bind mono-, di-, tri-, and tetra-ubiquitin in vitro but appear to bind to polyubiquitin with a higher affinity and it is thought that polyubiquitinated proteins represent the true in vivo binding substrates. As well, some UBA domains appear to homo and heterodimerize and to bind other substrates. Functionally, the UBA domain has been proposed to limit ubiquitin chain elongation and to target ubiquitinated proteins to the 26S proteasome for degradation. Evidence that ubiquitin binds to UBA domains leads to the prediction that the hydrophobic surface patch of UBA domains interacts with the hydrophobic surface on the five-stranded beta-sheet of ubiquitin (2).

1. http://pfam.xfam.org/family/PF00627

2. Mueller TD, Feigon J. (2002). Solution structures of UBA domains reveal a conserved hydrophobic surface for protein-protein interactions. J Mol Biol., 319(5):1243-55. PMID: 12079361