Ubox

Modified RING finger domain

• SMART accession number: SM00504
• Description: Modified RING finger domain, without the full complement of Zn2+-binding ligands. Probable involvement in E2-dependent ubiquitination.
• Interpro abstract (IPR003613):

  This entry represents the U-box domain.

  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, RING, 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, TPR, and armadillo repeat domains. In addition to a common organisation, the architecture of U-box and RING domains are similar. Both contain a central alpha-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 beta-sheet type arrangement involving the first surface exposed loop and the central alpha helix. The beta-sheet is stabilised 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 [ (PUBMED:20017557) (PUBMED:11435423) (PUBMED:18393940) ].

  The U-box is a domain of ~70 amino acids that is present in proteins from yeast to human. It consists of the beta-beta-alpha-beta-alpha-fold typical of U-box and RING domains (see PDB:2QIZ). The central alpha helix is flanked by two prominent surface-exposed loop regions. The characteristic network of hydrogen bonds within each loop stabilises the overall structure. The U-box protein appear to catalyze their own ubiquitination as well as that of heterologous substrate [ (PUBMED:20017557) (PUBMED:11435423) (PUBMED:18393940) ].

• GO process: protein ubiquitination (GO:0016567)
• GO function: ubiquitin-protein transferase activity (GO:0004842)

There are 15830 Ubox domains in 15767 proteins in SMART's nrdb database.

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Aravind L
• The WWE domain: a common interaction module in protein ubiquitination andADP ribosylation.
• Trends Biochem Sci. 2001; 26: 273-5

Sequence profile analysis was used to detect a conserved globular domainin several proteins including deltex, Trip12 and poly-ADP-ribosepolymerase homologs. It was named the WWE domain after its most conservedresidues and is predicted to mediate specific protein-protein interactionsin ubiquitin and ADP-ribose conjugation systems.

• Aravind L, Koonin EV
• The U box is a modified RING finger - a common domain in ubiquitination.
• Curr Biol. 2000; 10: 1324-1324

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
100.00	map04120	Ubiquitin mediated proteolysis

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with Ubox domain which could be assigned to a KEGG orthologous group, and not all proteins containing Ubox domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of Ubox domains in PDB

PDB code	Title
1n87	Solution structure of the U-box of Prp19
1t1h	NMR solution structure of the U box domain from AtPUB14, an armadillo repeat containing protein from Arabidopsis thaliana
1wgm	Solution structure of the U-box in human ubiquitin conjugation factor E4A
2bay	Crystal structure of the Prp19 U-box dimer
2c2l	Crystal structure of the CHIP U-box E3 ubiquitin ligase
2c2v	Crystal structure of the CHIP-UBC13-UEV1a complex
2f42	dimerization and U-box domains of Zebrafish C-terminal of HSP70 interacting protein
2kr4	U-box domain of the E3 Ubiquitin Ligase E4B
2kre	Solution structure of E4B/UFD2A U-Box domain
2oxq	Structure of the UbcH5 :CHIP U-box complex
2qiz	Structure of the yeast U-box-containing ubiquitin ligase Ufd2p
2qj0	Structure of the yeast U-box-containing ubiquitin ligase Ufd2p
3jb9	3JB9
3l1x	Crystal Structure of U-box Domain of Human E4B Ubiquitin Ligase
3l1z	Crystal structure of the U-BOX domain of human E4B ubiquitin ligase in complex with UBCH5C E2 ubiquitin conjugating enzyme
3m62	Crystal structure of Ufd2 in complex with the ubiquitin-like (UBL) domain of Rad23
3m63	Crystal structure of Ufd2 in complex with the ubiquitin-like (UBL) domain of Dsk2
4wz0	4WZ0
4wz2	4WZ2
4wz3	4WZ3
4xi1	4XI1
5gm6	5GM6
5gmk	5GMK
5lj5	5LJ5

Links (links to other resources describing this domain)

• INTERPRO: IPR003613