POU domain#Etymology

The acronym POU is derived from the names of three transcription

factors:

• the Pituitary-specific Pit-1
• the Octamer transcription factor proteins Oct-1 and Oct-2 (octamer sequence is ATGCAAAT)
• the neural Unc-86 transcription factor from Caenorhabditis elegans.

POU domain genes have been described in organisms as divergent as

Caenorhabditis elegans, Drosophila, Xenopus,

zebrafish and human but have not been yet identified in plants

and fungi.

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 and Oct-2 are members of POU2, while Unc-86 is a member of POU4. The six classes diverged early in animal evolution: POU1, POU3, POU4, and POU6 classes evolved before the last common ancestor of sponges and eumetazoans, POU2 evolved in the Bilatera, and POU5 appears to be unique to vertebrates.{{Cite journal|title = The Early Expansion and Evolutionary Dynamics of POU Class Genes|url= |journal = Molecular Biology and Evolution|date = 2014-12-01|issn = 0737-4038|pmc = 4245813|pmid = 25261405|pages = 3136–3147|volume = 31|issue = 12|doi = 10.1093/molbev/msu243|language = en|first1 = David A.|last1 = Gold|first2 = Ruth D.|last2 = Gates|first3 = David K.|last3 = Jacobs}}

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 the gram positive prokaryote Bacillus subtilis.{{cite journal | vauthors = D'Souza C, Nakano MM, Zuber P | title = Identification of comS, a gene of the srfA operon that regulates the establishment of genetic competence in Bacillus subtilis | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 91 | issue = 20 | pages = 9397–401 |date=September 1994 | pmid = 7937777 | pmc = 44819 | doi = 10.1073/pnas.91.20.9397

| doi-access = free }} Akin to the way that POU homeodomain

regulators lead to tissue differentiation in metazoans, this

transcription factor is critical for differentiation of a subpopulation

of B. subtilis into a state of genetic competence.

POU proteins are eukaryotic transcription factors containing a bipartite DNA binding domain referred to as the POU domain. The various members of the POU family have a wide variety of functions, all of which are related to the function of the neuroendocrine system{{cite journal | vauthors = Assa-Munt N, Mortishire-Smith RJ, Aurora R, Herr W, Wright PE | title = The solution structure of the Oct-1 POU-specific domain reveals a striking similarity to the bacteriophage lambda repressor DNA-binding domain | journal = Cell | volume = 73 | issue = 1 | pages = 193–205 | date = Apr 1993 | pmid = 8462099 | doi = 10.1016/0092-8674(93)90171-L | s2cid = 24276357 }} and the development of an organism.{{cite journal | vauthors = Andersen B, Rosenfeld MG | title = POU domain factors in the neuroendocrine system: lessons from developmental biology provide insights into human disease | journal = Endocrine Reviews | volume = 22 | issue = 1 | pages = 2–35 | date = Feb 2001 | doi = 10.1210/edrv.22.1.0421 | pmid = 11159814 | doi-access = free }} Some other genes are also regulated, including those for immunoglobulin light and heavy chains (Oct-2),{{cite journal | vauthors = Petryniak B, Staudt LM, Postema CE, McCormack WT, Thompson CB | title = Characterization of chicken octamer-binding proteins demonstrates that POU domain-containing homeobox transcription factors have been highly conserved during vertebrate evolution | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 87 | issue = 3 | pages = 1099–1103 | date = Feb 1990 | pmid = 1967834 | pmc = 53418 | doi = 10.1073/pnas.87.3.1099 | doi-access = free }}{{cite journal | vauthors = Johnson WA, Hirsh J | title = Binding of a Drosophila POU-domain protein to a sequence element regulating gene expression in specific dopaminergic neurons | journal = Nature | volume = 343 | issue = 6257 | pages = 467–470 | date = Feb 1990 | pmid = 1967821 | doi = 10.1038/343467a0 | s2cid = 9315961 }} and trophic hormone genes, such as

those for prolactin and growth hormone (Pit-1).

The POU domain is a bipartite domain composed of two subunits separated by a non-conserved region of 15-55 aa. The N-terminal subunit is known as the POU-specific (POUs) domain ({{InterPro|IPR000327}}), while the C-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.{{cite journal | vauthors = Mathis JM, Simmons DM, He X, Swanson LW, Rosenfeld MG | title = Brain 4: a novel mammalian POU domain transcription factor exhibiting restricted brain-specific expression | journal = The EMBO Journal | volume = 11 | issue = 7 | pages = 2551–2561 | date = Jul 1992 | doi = 10.1002/j.1460-2075.1992.tb05320.x | pmid = 1628619 | pmc = 556730 }} The subdomains are connected by a flexible linker.{{cite journal | vauthors = Phillips K, Luisi B | title = The virtuoso of versatility: POU proteins that flex to fit | journal = Journal of Molecular Biology | volume = 302 | issue = 5 | pages = 1023–1039 | date = Oct 2000 | pmid = 11183772 | doi = 10.1006/jmbi.2000.4107 }}{{cite journal | vauthors = Klemm JD, Rould MA, Aurora R, Herr W, Pabo CO | title = Crystal structure of the Oct-1 POU domain bound to an octamer site: DNA recognition with tethered DNA-binding modules | journal = Cell | volume = 77 | issue = 1 | pages = 21–32 | date = Apr 1994 | pmid = 8156594 | doi = 10.1016/0092-8674(94)90231-3 | s2cid = 36371069 }}{{cite journal | vauthors = Jacobson EM, Li P, Leon-del-Rio A, Rosenfeld MG, Aggarwal AK | title = Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility | journal = Genes & Development | volume = 11 | issue = 2 | pages = 198–212 | date = Jan 1997 | pmid = 9009203 | doi = 10.1101/gad.11.2.198 | doi-access = free }} 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 of bacteriophage lambda repressor and other members of HTH_3 family.

Human genes encoding proteins containing the POU domain and related pseudogenes include:

• HDX;
• POU1F1;
• POU2F1; POU2F2; POU2F3;
• POU3F1; POU3F2; POU3F3; POU3F4;
• POU4F1; POU4F2; POU4F3;
• POU5F1; POU5F1B; POU5F1P2; POU5F1P3; POU5F1P4; POU5F1P5; POU5F1P6; POU5F1P7;
• POU5F2;
• POU6F1; POU6F2

{{Reflist|33em}}

{{InterPro content|IPR000327}}

{{Transcription factors|g3}}