POU (pronounced 'pow') is a family of eukaryotic transcription factors that have well-conserved homeodomains.[1] The Pou domain is a bipartite DNA binding domain found in these proteins.
| Pou domain - N-terminal to homeobox domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | Pou | ||||||||
| Pfam | PF00157 | ||||||||
| InterPro | IPR000327 | ||||||||
| PROSITE | PDOC00035 | ||||||||
| SCOP2 | 1oct / SCOPe / SUPFAM | ||||||||
| |||||||||
Etymology
editThe 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.
Diversity
editPOU 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.[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 the gram positive prokaryote Bacillus subtilis.[3] 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.
Function
editPOU 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[4] and the development of an organism.[5] Some other genes are also regulated, including those for immunoglobulin light and heavy chains (Oct-2),[6][7] and trophic hormone genes, such as those for prolactin and growth hormone (Pit-1).
Structure
editThe 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.[8] The subdomains are connected by a flexible 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 of bacteriophage lambda repressor and other members of HTH_3 family.[9][10]
Examples
editHuman genes encoding proteins containing the POU domain and related pseudogenes include:
References
edit- ^ 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. PMID 11183772.
- ^ Gold, David A.; Gates, Ruth D.; Jacobs, David K. (2014-12-01). "The Early Expansion and Evolutionary Dynamics of POU Class Genes". Molecular Biology and Evolution. 31 (12): 3136–3147. doi:10.1093/molbev/msu243. ISSN 0737-4038. PMC 4245813. PMID 25261405.
- ^ D'Souza C, Nakano MM, Zuber P (September 1994). "Identification of comS, a gene of the srfA operon that regulates the establishment of genetic competence in Bacillus subtilis". Proc. Natl. Acad. Sci. U.S.A. 91 (20): 9397–401. doi:10.1073/pnas.91.20.9397. PMC 44819. PMID 7937777.
- ^ 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. PMID 8462099. S2CID 24276357.
- ^ Andersen B, Rosenfeld MG (Feb 2001). "POU domain factors in the neuroendocrine system: lessons from developmental biology provide insights into human disease". Endocrine Reviews. 22 (1): 2–35. doi:10.1210/edrv.22.1.0421. PMID 11159814.
- ^ Petryniak B, Staudt LM, Postema CE, McCormack WT, Thompson CB (Feb 1990). "Characterization of chicken octamer-binding proteins demonstrates that POU domain-containing homeobox transcription factors have been highly conserved during vertebrate evolution". Proceedings of the National Academy of Sciences of the United States of America. 87 (3): 1099–1103. doi:10.1073/pnas.87.3.1099. PMC 53418. PMID 1967834.
- ^ 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. PMID 1967821. S2CID 9315961.
- ^ Mathis JM, Simmons DM, He X, Swanson LW, Rosenfeld MG (Jul 1992). "Brain 4: a novel mammalian POU domain transcription factor exhibiting restricted brain-specific expression". The EMBO Journal. 11 (7): 2551–2561. doi:10.1002/j.1460-2075.1992.tb05320.x. PMC 556730. PMID 1628619.
- ^ a b Phillips 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. PMID 11183772.
- ^ a b Klemm 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. PMID 8156594. S2CID 36371069.
- ^ Jacobson EM, Li P, Leon-del-Rio A, Rosenfeld MG, Aggarwal AK (Jan 1997). "Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility". Genes & Development. 11 (2): 198–212. doi:10.1101/gad.11.2.198. PMID 9009203.