POU domain-containing protein, class 4-related <p>POU proteins are eukaryotic transcription factors containing a bipartite DNA-binding domain referred to as the POU domain. The acronym POU (pronounced 'pow') is named after the pituitary-specific Pit-1, octamer-binding proteins Oct-1 and Oct-2, and the neural Unc-86 from <taxon tax_id="6239">Caenorhabditis elegans</taxon>. The POU domain is a 70 to 75 amino-acid region found upstream of a homeobox domain in some transcription factors. POU domain genes have been described in organisms as divergent as C. elegans, <taxon tax_id="7227">Drosophila melanogaster</taxon> (Fruit fly), <taxon tax_id="8355">Xenopus laevis</taxon> (African clawed frog), <taxon tax_id="7955">Danio rerio</taxon> (Zebrafish) (Brachydanio rerio) and <taxon tax_id="9606">Homo sapiens</taxon> (Human) but have not been yet identified in plants and fungi. The various members of the POU family have a wide variety of functions, all of which are related to the development of an organism [<cite idref="PUB00007263"/>].</p> <p>The POU domain is a bipartite domain composed of two subunits separated by a non-conserved region of 15-55 amino acids. The N-terminal subunit is known as POU-specific (POUs) domain (<db_xref db="INTERPRO" dbkey="IPR000327"/>) and a C-terminal homeodomain. Both subdomains contain the structural motif 'helix-turn-helix', which directly associates with the two components of bipartite DNA-binding sites. The 3-D structure of the POU-domain has been determined by multidimensional NMR [<cite idref="PUB00000889"/>] and X-ray crystallography to 3.0 A resolution [<cite idref="PUB00000905"/>]. The subdomains are connected by a flexible linker [<cite idref="PUB00007264"/>, <cite idref="PUB00000905"/>, <cite idref="PUB00007265"/>]. Despite of the lack of sequence homology, 3D structure of POUs is similar to 3D structure of bacteriophage lambda repressor and other members of HTH_3 family [<cite idref="PUB00007264"/>, <cite idref="PUB00000905"/>].</p> <p>POU domain containing proteins bind to specific DNA sequences to cause temporal and spatial regulation of genes. Including genes: involved in the regulation of neuronal development in the central nervous system of mammals [<cite idref="PUB00004053"/>]; immunoglobulin light and heavy chains (Oct-2) [<cite idref="PUB00004699"/>]; and those for prolactin and growth hormone (Pit-1). Both elements of the POU-domain are required for high affinity sequence-specific DNA-binding. The domain may also be involved in protein-protein interactions [<cite idref="PUB00001223"/>].</p> <p>POU4-related transcription factors preferentially bind to the recognition sequence which consists of two distinct half-sites, ('GCAT') and ('TAAT'), separated by a nonconserved spacer region of 0, 2, or 3 nucleotides. Many are expressed at high levels in the brain including Brn-3A, Brn-3B, Brn-3C. BRN3A, -3B, -3C play a roles in the regulation of specific gene expression within a subset of neuronal lineages and play a role in determining or maintaining the identities of a small subset of visual system neurons.</p>