ATPase Family, AAA Domain Containing Protein 2 (ATAD2)

The deduced 1,390-amino acid protein contains an N-terminal acidic region, followed by 2 AAA ATPase domains, and a bromodomain. Northern blot analysis detected ANCCA transcripts of 5 and 4.7 kb in estrogen-stimulated breast cancer cells. Western blot analysis revealed a 170-kD ANCCA protein. Immunofluorescence analysis showed ANCCA localized primarily in the nucleus.

ANCCA bound and hydrolyzed ATP and was critical for recruitment of coregulator CBP and histone hyperacetylation at the ER target chromatin. Mutation of lys473 and glu532 within the Walker A and Walker B motifs, respectively, of AAA domain-1 of ANCCA rendered ANCCA defective as a coactivator in mediating estrogen induction of gene expression.