|PROSITE documentation PDOC00034 [for PROSITE entry PS51057]|
The paired domain is a ~126 amino acid DNA-binding domain, which is found in eukaryotic transcription regulatory proteins involved in embryogenesis. The domain was originally described as the 'paired box' in the Drosophila protein paired (prd) [1,2]. The paired DNA-binding domain is generally located in the N-terminal part. An octapeptide  and/or a homeodomain (see <PDOC00027>) can occur C-terminal to the paired DNA-binding domain, as well as a Pro-Ser-Thr-rich C-terminus. Paired DNA-binding domain proteins can function as transcription repressors or activators. The paired DNA-binding domain contains three subdomains, which show functional differences in DNA-binding.
The crystal structures of prd and Pax proteins show that the DNA-bound paired domain is bipartite, consisting of an N-terminal subdomain (PAI or NTD) and a C-terminal subdomain (RED or CTD), connected by a linker (see <PDB:1K78>). PAI and RED each form a three-helical fold, with the most C-terminal helices comprising a helix-turn-helix (HTH) motif that binds the DNA major groove. In addition, the PAI subdomain encompasses an N-terminal β-turn and β-hairpin, also named 'wing', participating in DNA-binding. The linker can bind into the DNA minor groove. Different Pax proteins and their alternatively spliced isoforms use different (sub)domains for DNA-binding to mediate the specificity of sequence recognition [4,5].
Some proteins known to contain a paired DNA-binding domain:
We use the region spanning positions 34 to 50 of the paired DNA-binding domain as a signature pattern. This conserved region spans the DNA-binding HTH located in the N-terminal subdomain. We also developed a profile that covers the entire paired DNA-binding domain, including the PAI and RED subdomains and which allows a more sensitive detection.Last update:
Jun 2019 / Text revised.
PROSITE methods (with tools and information) covered by this documentation:
|1||Authors||Bopp D. Burri M. Baumgartner S. Frigerio G. Noll M.|
|Title||Conservation of a large protein domain in the segmentation gene paired and in functionally related genes of Drosophila.|
|2||Authors||Baumgartner S. Bopp D. Burri M. Noll M.|
|Title||Structure of two genes at the gooseberry locus related to the paired gene and their spatial expression during Drosophila embryogenesis.|
|Source||Genes Dev. 1:1247-1267(1987).|
|3||Authors||Eberhard D. Jimenez G. Heavey B. Busslinger M.|
|Title||Transcriptional repression by Pax5 (BSAP) through interaction with corepressors of the Groucho family.|
|Source||EMBO J. 19:2292-2303(2000).|
|Title||Genetic and biochemical diversity in the Pax gene family.|
|Source||Biochem. Cell Biol. 78:629-638(2000).|
|5||Authors||Apuzzo S. Abdelhakim A. Fortin A.S. Gros P.|
|Title||Cross-talk between the paired domain and the homeodomain of Pax3: DNA binding by each domain causes a structural change in the other domain, supporting interdependence for DNA Binding.|
|Source||J. Biol. Chem. 279:33601-33612(2004).|