|PROSITE documentation PDOC51698|
The molecular mechanism underlying the transfer of ubiquitin (Ub) to a substrate consists of three key enzymatic steps. First, ubiquitin itself is adenylated at its C-terminal glycine residue by an activating enzyme (E1). Second, the adenylated Ub forms a covalent linkage to a conjugating enzyme (E2). Finally, a ligating enzyme (E3) recruits both the Ub-charged E2 species and the target protein. There are three classes of E3 enzymes: HECT (see <PDOC50237>), RING (see <PDOC00449>), and U-box, which are distinguished on the basis of their E2-recruiting domains. The U-box and RING classes of E3 ligases act as scaffolding molecules that recruit and colocalize both a Ub-charged E2 and the substrate concomitantly. The recruitement of substrate in these proteins involves protein interaction modules such as a WD-40 repeat (see <PDOC00574>), TPR (see <PDOC50005>), and armadillo repeat (see <PDOC50176>) domains. In addition to a common organization, the architecture of U-box and RING domains are similar. Both contain a central α-helix flanked by two surface-exposed loops arranged in a cross-brace formation. the structure of RING domains is built around two zinc binding sites that are critical to its stability. In contrast, U-boxes do not bind zinc but have evolved instead networks of hydrogen bonds and salt bridges in corresponding location in the structure. Other similarities between these two domains include an antiparallel β-sheet type arrangement involving the first surface exposed loop and the central α helix. The β-sheet is stabilized by highly conserved hydrophobic residues responsible for the core packing and stability of the molecule. Most U-box and RING domain structures also contain an elongated C-terminal helix. The physical basis and physiological rationale for evolving distinct U-box and RING E3 ligases are not yet known [1,2,3].
The U-box is a domain of ~70 amino acids that is present in proteins from yeast to human. It consists of the ββαβα-fold typical of U-box and RING domains (see <PDB:2QIZ>). The central α-helix is flanked by two prominent surface-exposed loop regions. The characteristic network of hydrogen bonds within each loop stabilizes the overall structure. The U-box protein appear to catalyze their own ubiquitination as well as that of heterologous substrate [1,2,3].
The profile we developed covers the entire U-box domain.Last update:
December 2013 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Nordquist K.A. Dimitrova Y.N. Brzovic P.S. Ridenour W.B. Munro K.A. Soss S.E. Caprioli R.M. Klevit R.E. Chazin W.J.|
|Title||Structural and functional characterization of the monomeric U-box domain from E4B.|
|2||Authors||Hatakeyama S. Yada M. Matsumoto M. Ishida N. Nakayama K.-I.|
|Title||U box proteins as a new family of ubiquitin-protein ligases.|
|Source||J. Biol. Chem. 276:33111-33120(2001).|
|3||Authors||Wiborg J. O'Shea C. Skriver K.|
|Title||Biochemical function of typical and variant Arabidopsis thaliana U-box E3 ubiquitin-protein ligases.|
|Source||Biochem. J. 413:447-457(2008).|