Comparisons of POU domain genes across the animals suggests that the family can be divided into six major classes (POU1-POU6).Pit-1 is part of the POU1 class,Oct-1 andOct-2 are members of POU2, while Unc-86 is a member ofPOU4. The six classes diverged early in animal evolution: POU1, POU3, POU4, and POU6 classes evolved before the last common ancestor ofsponges andeumetazoans, POU2 evolved in theBilatera, and POU5 appears to be unique tovertebrates.[2]
There is a surprisingly high degree of amino acid sequence conservation (37%-42%) of POU homeodomains to the transcriptional regulator comS, the competence protein from thegram positiveprokaryoteBacillus subtilis.[3] Akin to the way that POU homeodomain regulators lead to tissue differentiation inmetazoans, this transcription factor is critical for differentiation of a subpopulation ofB. subtilis into a state ofgenetic competence.
The POU domain is a bipartite domain composed of two subunits separated by a non-conserved region of 15-55 aa. TheN-terminal subunit is known as the POU-specific (POUs) domain (InterPro: IPR000327), while theC-terminal subunit is a homeobox domain (InterPro: IPR007103). 3D structures of complexes including both POU subdomains bound to DNA are available. Both subdomains contain the structural motif 'helix-turn-helix', which directly associates with the two components of bipartite DNA binding sites, and both are required for high affinity sequence-specific DNA-binding. The domain may also be involved in protein-protein interactions.[8] The subdomains are connected by aflexible linker.[9][10][11] In proteins a POU-specific domain is always accompanied by a homeodomain. Despite the lack of sequence homology, 3D structure of POUs is similar to 3D structure ofbacteriophage lambda repressor and other members of HTH_3 family.[9][10]
^Phillips K, Luisi B (Oct 2000). "The virtuoso of versatility: POU proteins that flex to fit".Journal of Molecular Biology.302 (5):1023–39.doi:10.1006/jmbi.2000.4107.PMID11183772.
^Assa-Munt N, Mortishire-Smith RJ, Aurora R, Herr W, Wright PE (Apr 1993). "The solution structure of the Oct-1 POU-specific domain reveals a striking similarity to the bacteriophage lambda repressor DNA-binding domain".Cell.73 (1):193–205.doi:10.1016/0092-8674(93)90171-L.PMID8462099.S2CID24276357.
^Johnson WA, Hirsh J (Feb 1990). "Binding of a Drosophila POU-domain protein to a sequence element regulating gene expression in specific dopaminergic neurons".Nature.343 (6257):467–470.doi:10.1038/343467a0.PMID1967821.S2CID9315961.
^abPhillips K, Luisi B (Oct 2000). "The virtuoso of versatility: POU proteins that flex to fit".Journal of Molecular Biology.302 (5):1023–1039.doi:10.1006/jmbi.2000.4107.PMID11183772.
^abKlemm JD, Rould MA, Aurora R, Herr W, Pabo CO (Apr 1994). "Crystal structure of the Oct-1 POU domain bound to an octamer site: DNA recognition with tethered DNA-binding modules".Cell.77 (1):21–32.doi:10.1016/0092-8674(94)90231-3.PMID8156594.S2CID36371069.
