| Type: | Family | Name: | POU domain-containing protein, class 5 |
| Description: | 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 Caenorhabditis elegans. 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, Drosophila melanogaster(Fruit fly), Xenopus laevis(African clawed frog), Danio rerio(Zebrafish) (Brachydanio rerio) and Homo sapiens(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 [].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 () 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 [] and X-ray crystallography to 3.0 A resolution []. The subdomains are connected by a flexible linker [, , ]. 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 [, ].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 []; immunoglobulin light and heavy chains (Oct-2) []; 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 [].POU domain class 5 includes the Oct3/4 gene. Mice with targeted disruption of the Oct3/4 gene developed to the blastocyst stage; however, the inner cell mass cells were not pluripotent. Instead, they were restricted to differentiation along the extraembryonic trophoblast lineage. Furthermore, in the absence of a true inner cell mass, trophoblast proliferation was not maintained in Oct3/4 -/- embryos. Expansion of trophoblast precursors was restored by addition of fibroblast growth factor-4, an Oct4 target gene product. It is thought that Oct4 determines paracrine growth factor signalling from stem cells to the trophectoderm with the activity of Oct4 essential for the identity of the pluripotential founder cell population in the mammalian embryo. Critical amounts of OCT3/4 are required to sustain stem cell self-renewal, with increased or decreased amounts inducing divergent developmental programs. It has been suggested that OCT3/4 is a master regulator of pluripotency and controls lineage commitment. | Short Name: | POU_dom_5 |
