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Gene Review

UBA3  -  NEDD8-activating protein UBA3

Saccharomyces cerevisiae S288c

Synonyms: NEDD8-activating enzyme E1 catalytic subunit, RUB1-activating enzyme E1, Ubiquitin-activating enzyme E1 3, Ubiquitin-like protein-activating enzyme, YP9499.21, ...
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High impact information on UBA3

  • By modeling ubiquitin into the NEDD8 binding site and performing mutational analysis, we identify a single conserved arginine in APPBP1-UBA3 that acts as a selectivity gate, preventing misactivation of ubiquitin by NEDD8's E1 [1].
  • To determine the role of the NEDD8 system in mammals, we generated mice deficient in Uba3 gene that encodes a catalytic subunit of NEDD8-activating enzyme [2].
  • Human AppBp1-Uba3 follows hyperbolic kinetics for HsUbc12 transthiolation with 125I-Nedd8 (kcat = 3.5 +/- 0.2 s-1), yielding Km values for ATP (103 +/- 12 microm), 125I-Nedd8 (0.95 +/- 0.18 microm), and HsUbc12 (43 +/- 13 nm) similar to those for ubiquitin activation by Uba1 [3].
  • The human UBA3 gene is located on chromosome 3p13 and gave rise to a 2.2-kilobase pair transcript that was detected in all tissues [4].
  • Whereas the amino acid sequence of UBA2 is nearly identical to UBA1, the sequence of UBA3 is significantly different [5].

Biological context of UBA3


Associations of UBA3 with chemical compounds

  • Thus, Uba3 inhibits transcription induced by steroid hormone receptors through a novel mechanism that involves the neddylation pathway [8].

Enzymatic interactions of UBA3


Analytical, diagnostic and therapeutic context of UBA3

  • Sequence analysis revealed that Uba3 contains multiple nuclear receptor (NR)-interacting motifs (NR boxes), which are known to mediate interactions between coregulatory proteins and ligand-activated NRs [8].


  1. The structure of the APPBP1-UBA3-NEDD8-ATP complex reveals the basis for selective ubiquitin-like protein activation by an E1. Walden, H., Podgorski, M.S., Huang, D.T., Miller, D.W., Howard, R.J., Minor, D.L., Holton, J.M., Schulman, B.A. Mol. Cell (2003) [Pubmed]
  2. The NEDD8 system is essential for cell cycle progression and morphogenetic pathway in mice. Tateishi, K., Omata, M., Tanaka, K., Chiba, T. J. Cell Biol. (2001) [Pubmed]
  3. Conservation in the mechanism of Nedd8 activation by the human AppBp1-Uba3 heterodimer. Bohnsack, R.N., Haas, A.L. J. Biol. Chem. (2003) [Pubmed]
  4. Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway. Gong, L., Yeh, E.T. J. Biol. Chem. (1999) [Pubmed]
  5. Multiple forms of ubiquitin-activating enzyme E1 from wheat. Identification of an essential cysteine by in vitro mutagenesis. Hatfield, P.M., Vierstra, R.D. J. Biol. Chem. (1992) [Pubmed]
  6. The NEDD8 pathway is required for proteasome-mediated degradation of human estrogen receptor (ER)-alpha and essential for the antiproliferative activity of ICI 182,780 in ERalpha-positive breast cancer cells. Fan, M., Bigsby, R.M., Nephew, K.P. Mol. Endocrinol. (2003) [Pubmed]
  7. But1 and But2 proteins bind to Uba3, a catalytic subunit of E1 for neddylation, in fission yeast. Yashiroda, H., Tanaka, K. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  8. The activating enzyme of NEDD8 inhibits steroid receptor function. Fan, M., Long, X., Bailey, J.A., Reed, C.A., Osborne, E., Gize, E.A., Kirk, E.A., Bigsby, R.M., Nephew, K.P. Mol. Endocrinol. (2002) [Pubmed]
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