Home  |  Contact
PROSITE documentation PDOC50030 [for PROSITE entry PS50030]

Ubiquitin-associated domain (UBA) profile





Description

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 [3].

Some proteins known to contain an UBA domain are listed below:

  • Mammalian E2-25K and several other ubiquitin-conjugating enzymes (E2), catalyzing the second step in protein ubiquitination.
  • Drosophila hyperplastic discs protein, a putative ubiquitin-protein ligase (E3), catalyzing the third and final step in protein ubiquitination.
  • Eukaryotic ubiquitin isopeptidase T and several other ubiquitin C-terminal hydrolases, catalyzing regulatory protein de-ubiquitination.
  • Yeast RAD23 and its mammalian homologues. These proteins act in UV excision repair and contain a N-terminal domain similar to ubiquitin itself.
  • Yeast DSK2. It is required for spindle pole body duplication. This protein contains an N-terminal domain similar to ubiquitin itself.
  • Mammalian proto-oncogene c-cbl, a protein interacting with multiple signal transduction factors. Cbl has recently been shown to undergo regulatory ubiquination upon macrophage stimulation.
  • Drosophila Ref(2)P protein and its mammalian homologues.
  • A large family of SNF1-like kinases from various plants and other organisms.

The profile we developed covers the entire UBA domain.

Expert(s) to contact by email:

Hofmann K.

Last update:

March 2003 / First entry.

Technical section

PROSITE method (with tools and information) covered by this documentation:

UBA, PS50030; Ubiquitin-associated domain (UBA) profile  (MATRIX)


References

1AuthorsHofmann K. Bucher P.
TitleThe UBA domain: a sequence motif present in multiple enzyme classes of the ubiquitination pathway.
SourceTrends Biochem. Sci. 21:172-173(1996).
PubMed ID8871400

2AuthorsBuchberger A.
TitleFrom UBA to UBX: new words in the ubiquitin vocabulary.
SourceTrends Cell Biol. 12:216-221(2002).
PubMed ID12062168

3AuthorsMueller T.D. Feigon J.
TitleSolution structures of UBA domains reveal a conserved hydrophobic surface for protein-protein interactions.
SourceJ. Mol. Biol. 319:1243-1255(2002).
PubMed ID12079361
DOI10.1016/S0022-2836(02)00302-9



PROSITE is copyright. It is produced by the SIB Swiss Institute Bioinformatics. There are no restrictions on its use by non-profit institutions as long as its content is in no way modified. Usage by and for commercial entities requires a license agreement. For information about the licensing scheme send an email to
Prosite License or see: prosite_license.html.

Miscellaneous

View entry in original PROSITE document format
View entry in raw text format (no links)