|PROSITE documentation PDOC50030 [for PROSITE entry PS50030]|
Covalent modification of proteins by the small, evolutionary conserved protein ubiquitin (see <PDOC00271>) plays a central role in a variety of cellular processes, including bulk protein degradation, cell-cycle control, stress response, DNA repair, signal transduction, transcriptional regulation and vesicular traffic. A cascade of three enzymes (called E1, E2 and E3) catalyzes the conjugation of ubiquitin to lysine side-chains of target proteins. Ubiquitination is a reversible process: several specific ubiquitin carboxy-terminal hydrolases (UBPs) can remove ubiquitin from proteins. The variety of cellular processes regulated by ubiquitination demands a high substrate specificity of the ubiquitination machinery as well as the existence of diverse downstream effector proteins interacting with ubiquitinated substrates. Most of these cellular effectors are characterized by a modular composition of ubiquitin-binding motifs and further domains mediating specific functions. The ubiquitin-associated (UBA) domain is a short sequence motif of ~45 amino acid residues that was initially identified in E2s, E3s, UBPs and several other proteins having connections to ubiquitin and the ubiquitination pathway. The UBA domain was latter found to occur frequently either as a single copy or as multiple copies in tandem arrangement in proteins found in all eukaryotes. In addition to many enzymes of the ubiquitination pathway, the UBA domain occurs in UV excision repair proteins and protein kinases involved in cell-signaling pathways and cell-cycle control. The UBA domain has been shown to bind ubiquitin but also proteins without ubiquitin-like domains and lacking an obvious link to ubiquitin, such as HIV Vpr, 3-methyladenine DNA glycosylase (MPG) or the nuclear mRNA export factor TAP/Mex67 [1,2,3].
The three dimensional structure of the UBA domain is a compact three-helix bundle with an unusually large hydrophobic surface patch (see <PDBD:1DV0>). It has been proposed that this hydrophobic surface patch is a common protein-interacting surface present in diverse UBA domains .
Some proteins known to contain an UBA domain are listed below:
The profile we developed covers the entire UBA domain.Expert(s) to contact by email:
March 2003 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Hofmann K. Bucher P.|
|Title||The UBA domain: a sequence motif present in multiple enzyme classes of the ubiquitination pathway.|
|Source||Trends Biochem. Sci. 21:172-173(1996).|
|Title||From UBA to UBX: new words in the ubiquitin vocabulary.|
|Source||Trends Cell Biol. 12:216-221(2002).|
|3||Authors||Mueller T.D. Feigon J.|
|Title||Solution structures of UBA domains reveal a conserved hydrophobic surface for protein-protein interactions.|
|Source||J. Mol. Biol. 319:1243-1255(2002).|