Protein Degradation: UBA Domain

Domain Binding and Function

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. 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.

Structure Reference

1. Mueller, T.D. and Feigon, J. (2002) J. Mol. Biol. 319 (5), 1243–1255.

Examples of Domain Proteins

Binding Examples

UBA Domain Proteins	Binding Partners
HHR23A	mono and polyubiquitin Rad23 (homodimerization) HHR23A (heterodimerization) HIV Vpr
c-Cbl	unknown
HIP-2 E2 ubiquitin-conjugating enzyme	unknown