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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UBA Ubiquitin associated domain

SMART accession number:	SM00165
Description:	Present in Rad23, SNF1-like kinases. The newly-found UBA in p62 is known to bind ubiquitin.
Interpro abstract (IPR015940):	UBA domains are a commonly occurring sequence motif of approximately 45 amino acid residues that are found in diverse proteins involved in the ubiquitin/proteasome pathway, DNA excision-repair, and cell signalling via protein kinases [(PUBMED:8871400)]. The human homologue of yeast Rad23A is one example of a nucleotide excision-repair protein that contains both an internal and a C-terminal UBA domain. The solution structure of human Rad23A UBA(2) showed that the domain forms a compact three-helix bundle [(PUBMED:9846873)]. Comparison of the structures of UBA(1) and UBA(2) reveals that both form very similar folds and have a conserved large hydrophobic surface patch which may be a common protein-interacting surface present in diverse UBA domains. Evidence that ubiquitin binds to UBA domains leads to the prediction that the hydrophobic surface patch of UBA domains interacts with the hydrophobic surface on the five-stranded beta-sheet of ubiquitin [(PUBMED:12079361)]. This domain is similar in sequence to the N-terminal domain of translation elongation factor EF1B (or EF-Ts) from bacteria, mitochondria and chloroplasts. More information about EF1B (EF-Ts) proteins can be found at Protein of the Month: Elongation Factors [].
Family alignment:	View or CHROMA formatCLUSTALW formatMSF formatFASTA formatPIR format

There are 3186 UBA domains in 2547 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 UBA domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with UBA 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

• Cellular role (predicted cellular role)

• Binding / catalysis: protein-binding, ubiquitin-binding

• Literature (relevant references for this domain)

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

  • Dieckmann T, Withers-Ward ES, Jarosinski MA, Liu CF, Chen IS, Feigon J
  • Structure of a human DNA repair protein UBA domain that interacts with HIV-1 Vpr.
  • Nat Struct Biol. 1998; 5: 1042-7
  • Display abstract

  • The HIV-1 protein Vpr is critical for a number of viral functions including a unique ability to arrest T-cells at a G2/M checkpoint and induce subsequent apoptosis. It has been shown to interact specifically with the second UBA (ubiquitin associated) domain found in the DNA repair protein HHR23A, a highly evolutionarily conserved protein. This domain is a commonly occurring sequence motif in some members of the ubiquitination pathway, UV excision repair proteins, and certain protein kinases. The three dimensional structure of the UBA domain, determined by NMR spectroscopy, is presented. The protein domain forms a compact three-helix bundle. One side of the protein has a hydrophobic surface that is the most likely Vpr target site.

  • Grishin NV
  • The R3H motif: a domain that binds single-stranded nucleic acids.
  • Trends Biochem Sci. 1998; 23: 329-30

  • Schultz J, Milpetz F, Bork P, Ponting CP
  • SMART, a simple modular architecture research tool: identification of signaling domains.
  • Proc Natl Acad Sci U S A. 1998; 95: 5857-64
  • Display abstract

  • Accurate multiple alignments of 86 domains that occur in signaling proteins have been constructed and used to provide a Web-based tool (SMART: simple modular architecture research tool) that allows rapid identification and annotation of signaling domain sequences. The majority of signaling proteins are multidomain in character with a considerable variety of domain combinations known. Comparison with established databases showed that 25% of our domain set could not be deduced from SwissProt and 41% could not be annotated by Pfam. SMART is able to determine the modular architectures of single sequences or genomes; application to the entire yeast genome revealed that at least 6.7% of its genes contain one or more signaling domains, approximately 350 greater than previously annotated. The process of constructing SMART predicted (i) novel domain homologues in unexpected locations such as band 4.1-homologous domains in focal adhesion kinases; (ii) previously unknown domain families, including a citron-homology domain; (iii) putative functions of domain families after identification of additional family members, for example, a ubiquitin-binding role for ubiquitin-associated domains (UBA); (iv) cellular roles for proteins, such predicted DEATH domains in netrin receptors further implicating these molecules in axonal guidance; (v) signaling domains in known disease genes such as SPRY domains in both marenostrin/pyrin and Midline 1; (vi) domains in unexpected phylogenetic contexts such as diacylglycerol kinase homologues in yeast and bacteria; and (vii) likely protein misclassifications exemplified by a predicted pleckstrin homology domain in a Candida albicans protein, previously described as an integrin.

  • Hofmann K, Bucher P
  • The UBA domain: a sequence motif present in multiple enzyme classes of the ubiquitination pathway.
  • Trends Biochem Sci. 1996; 21: 172-3
• Metabolism (metabolic pathways involving proteins which contain this domain)

• Click the image to view the interactive version of the map in iPath

  % proteins involved KEGG pathway ID Description 22.35 map04120 Ubiquitin mediated proteolysis 12.94 map04012 ErbB signaling pathway 12.94 map04660 T cell receptor signaling pathway 12.94 map04630 Jak-STAT signaling pathway 12.94 map05220 Chronic myeloid leukemia 12.94 map04910 Insulin signaling pathway 9.41 map05040 Huntington's disease 1.18 map00562 Inositol phosphate metabolism 1.18 map00632 Benzoate degradation via CoA ligation 1.18 map03030 DNA replication 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 UBA domain which could be assigned to a KEGG orthologous group, and not all proteins containing UBA 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 UBA domains in PDB

  PDB code	Main view	Title
  1dv0		Refined nmr solution structure of the c-terminal uba domain of the human homologue of rad23a (hhr23a)
  1f4i		Solution structure of the hhr23a uba(2) mutant p333e, deficient in binding the hiv-1 accessory protein vpr
  1ify		Solution structure of the internal uba domain of hhr23a
  1oqy		Structure of the dna repair protein hhr23a
  1q02		Nmr structure of the uba domain of p62 (sqstm1)
  1qze		Hhr23a protein structure based on residual dipolar coupling data
  1veg		Solution structure of rsgi ruh-012, a uba domain from mouse cdna
  1vej		Solution structure of rsgi ruh-016, a uba domain from mouse cdna
  1vek		Solution structure of rsgi ruh-011, a uba domain from arabidopsis cdna
  1vg5		Solution structure of rsgi ruh-014, a uba domain from arabidopsis cdna
  1whc		Solution structure of rsgi ruh-027, a uba domain from mouse cdna
  1wiv		Solution structure of rsgi ruh-023, a uba domain from arabidopsis cdna
  1wj7		Solution structure of rsgi ruh-015, a uba domain from mouse cdna
  1wji		Solution structure of the uba domain of human tudor domain containing protein 3
  1wr1		The complex sturcture of dsk2p uba with ubiquitin
  1y8g		Catalytic and ubiqutin-associated domains of mark2/par-1: inactive double mutant with selenomethionine
  1yla		Ubiquitin-conjugating enzyme e2-25 kda (huntington interacting protein 2)
  1z96		Crystal structure of the mud1 uba domain
  1zmu		Catalytic and ubiqutin-associated domains of mark2/par-1: wild type
  1zmv		Catalytic and ubiqutin-associated domains of mark2/par-1: k82r mutant
  1zmw		Catalytic and ubiqutin-associated domains of mark2/par-1: t208a/s212a inactive double mutant
  2bwb		Crystal structure of the uba domain of dsk2 from s. cerevisiae
  2bwe		The crystal structure of the complex between the uba and ubl domains of dsk2
  2cpw		Solution structure of rsgi ruh-031, a uba domain from human cdna
  2cwb		Solution structure of the ubiquitin-associated domain of human bmsc-ubp and its complex with ubiquitin
  2d9s		Solution structure of rsgi ruh-049, a uba domain from mouse cdna
  2dag		Solution structure of the first uba domain in the human ubiquitin specific protease 5 (isopeptidase 5)
  2dah		Solution structure of the c-terminal uba domain in the human ubiquilin 3
  2dai		Solution structure of the first uba domain in the human ubiquitin associated domain containing 1 (ubadc1)
  2dak		Solution structure of the second uba domain in the human ubiquitin specific protease 5 (isopeptidase 5)
  2den		Solution structure of the ubiquitin-associated domain of human bmsc-ubp and its complex with ubiquitin
  2dkl		Solution structure of the uba domain in the human trinucleotide repeat containing 6c protein (htnrc6c)
  2do6		Solution structure of rsgi ruh-065, a uba domain from human cdna
  2ekk		Solution structure of ruh-074, a human uba domain
  2g3q		Solution structure of ede1 uba-ubiquitin complex
  2hak		Catalytic and ubiqutin-associated domains of mark1/par-1
  2jnh		Solution structure of the uba domain from cbl-b
  2juj		Solution structure of the uba domain from c-cbl
  2jy5		Nmr structure of ubiquilin 1 uba domain
  2jy6		Solution structure of the complex of ubiquitin and ubiquilin 1 uba domain
  2jy7		Nmr structure of the ubiquitin associated (uba) domain of p62 (sqstm1). rdc refined
  2jy8		Nmr structure of the ubiquitin associated (uba) domain of p62 (sqstm1) in complex with ubiquitin. rdc refined
  2k0b		Nmr structure of the uba domain of p62 (sqstm1)
  2o25		Ubiquitin-conjugating enzyme e2-25 kda complexed with sumo- 1-conjugating enzyme ubc9
  2oo9		Crystal structure of the uba domain from human c-cbl ubiquitin ligase
  2ooa		Crystal structure of the uba domain from cbl-b ubiquitin ligase
  2oob		Crystal structure of the uba domain from cbl-b ubiquitin ligase in complex with ubiquitin
  2pwq		Crystal structure of a putative ubiquitin conjugating enzyme from plasmodium yoelii
  2qnj		Kinase and ubiquitin-associated domains of mark3/par-1
  2qsf		Crystal structure of the rad4-rad23 complex
  2qsg		Crystal structure of rad4-rad23 bound to a uv-damaged dna
  2qsh		Crystal structure of rad4-rad23 bound to a mismatch dna
  2r0i		Crystal structure of a kinase mark2/par-1 mutant
  3e46		Crystal structure of ubiquitin-conjugating enzyme e2-25kda (huntington interacting protein 2) m172a mutant
  3f92		Crystal structure of ubiquitin-conjugating enzyme e2-25kda (huntington interacting protein 2) m172a mutant crystallized at ph 8.5
  3fe3		Crystal structure of the kinase mark3/par-1: t211a-s215a double mutant

• Links (links to other resources describing this domain)

• PFAM	UBA
  INTERPRO	IPR015940

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