ATAD2b (also known as KIAA1240) is an eukaryotic protein located in the nucleus that contains an AAA domain and a bromodomain. AAA ATPase domains use the energy of adenosine tri-phosphate (ATP) binding to participate in cellular activities as diverse as cell cycle control, signal transduction, disassembly of macromolecular complexes and regulation of gene expression. Bromodomains bind acetyl-lysine motifs and are thought to regulate protein–protein interactions in chromatin remodeling and transcriptional control. In humans, ATAD2B is an E2F target gene that binds to the MYC oncogene. High ATAD2b levels correlate with a higher risk of distant recurrence in breast cancer, and mutation of the bromodomain in ATAD2b impairs the binding between ATAD2b and certain acetylated histone tails.
Function
Disease
AAA ATPase Domain
The AAA domains share a common conserved module of approximately 230 amino acid residues. This is a large, functionally diverse protein family belonging to the AAA superfamily of ring-shaped P-loop NTPases, which exert their activity through the energy-dependent remodeling or translocation of macromolecules. Members of the AAA family are found in all organisms and they are essential for many cellular functions. They are involved in processes such as DNA replication, protein degradation, membrane fusion, microtubule severing, peroxisome biogenesis, signal transduction and the regulation of gene expression. ATP hydrolysis by AAA ATPases involves a nucleophilic attack on the ATP gamma-phosphate by an activated water molecule, leading to movement of the N-terminal and C-terminal AAA subdomains relative to each other. This movement allows the exertion of mechanical force, amplified by other ATPase domains within the same oligomeric structure.
Bromodomain
Bromodomains contain about 110 residues, recognize acetylated lysine side chains mainly in histones and are thus involved in transcriptional regulation. In the human genome there are 46 proteins with a total of 61 different bromodomains, with up to six bromodomains per protein. All bromodomains show a conserved four-helix bundle topology in which the ZA-loop and BC-loop connect the first two α helices (called Z and A) and last two α helices (called B and C), respectively. The acetyl-lysine binding site is very similar in all structures of bromodomains. The BC-loop contributes the evolutionary conserved asparagine side chain which acts as hydrogen bond donor to the acetylated lysine side chain. There are also two conserved tyrosine residues present in the ZA-loop and BC-loop.
Relevance
Structural highlights
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