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

• We now report the derived amino acid sequence of two additional members of this gene family (UBA2 and UBA3) [5].
• Here we report that Uba3-mediated inhibition of ERalpha transactivation function is due to increased receptor protein turnover [6].
• But1 and But2 proteins bind to Uba3, a catalytic subunit of E1 for neddylation, in fission yeast [7].
• Using the two-hybrid system, we isolated novel genes from the Schizosaccharomyces pombe cDNA library whose products bind to Uba3, which is a catalytic protein for E1-like activity of the NEDD8 pathway [7].

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

• Nevertheless, the protein encoded by UBA3 catalyzes the ATP-dependent activation of ubiquitin in vitro [5].

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].

References