Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2012) Nucleic Acids Res , doi:10.1093/nar/gkr931

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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):	Quality control of intracellular proteins is essential for cellular homeostasis. Molecular chaperones recognise and contribute to the refolding of misfolded or unfolded proteins, whereas the ubiquitin-proteasome system mediates the degradation of such abnormal proteins. Ubiquitin-protein ligases (E3s) determine the substrate specificity for ubiquitylation and have been classified into HECT and RING-finger families. More recently, however, U-box proteins, which contain a domain (the U box) of about 70 amino acids that is conserved from yeast to humans, have been identified as a new type of E3 [(PUBMED:12944364)]. Members of the U-box family of proteins constitute a class of ubiquitin-protein ligases (E3s) distinct from the HECT-type and RING finger-containing E3 families [(PUBMED:12944364)]. Using yeast two-hybrid technology, all mammalian U-box proteins have been reported to interact with molecular chaperones or co-chaperones, including Hsp90, Hsp70, DnaJc7, EKN1, CRN, and VCP. This suggests that the function of U box-type E3s is to mediate the degradation of unfolded or misfolded proteins in conjunction with molecular chaperones as receptors that recognise such abnormal proteins [(PUBMED:15115282), (PUBMED:15189447)]. Unlike the RING finger domain, IPR001841, that is stabilised by Zn2+ ions coordinated by the cysteines and a histidine, the U-box scaffold is probably stabilised by a system of salt-bridges and hydrogen bonds. The charged and polar residues that participate in this network of bonds are more strongly conserved in the U-box proteins than in classic RING fingers, which supports their role in maintaining the stability of the U box. Thus, the U box appears to have evolved from a RING finger domain by appropriation of a new set of residues required to stabilise its structure, concomitant with the loss of the original, metal-chelating residues [(PUBMED:10704423)].
GO process:	protein ubiquitination (GO:0016567)
GO component:	ubiquitin ligase complex (GO:0000151)
GO function:	ubiquitin-protein ligase activity (GO:0004842)
Family alignment:	View or CHROMA formatCLUSTALW formatMSF formatFASTA formatPIR format

There are 1335 Ubox domains in 1330 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a Ubox domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with Ubox domain is also avaliable.

  Useful shortcuts: Expand all nodes or Collapse tree
  Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes

• 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
  • Display abstract

  • 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	Main view	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
  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

• Links (links to other resources describing this domain)

• INTERPRO	IPR003613

Send comments to Ivica Letunic