POU domain

Pou domain - N-terminal to homeobox domain
Identifiers
Symbol Pou
Pfam PF00157
InterPro IPR000327
PROSITE PDOC00035
SCOP 1oct
SUPERFAMILY 1oct

POU (pronounced 'pow') is a family of proteins that have well-conserved homeodomains.[1]

Etymology

The acronym POU is derived from the names of three transcription factors:

Diversity

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.[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

POU proteins are eukaryotic transcription factors containing a bipartite DNA binding domain referred to as the POU domain. The acronym POU (pronounced 'pow') is derived from the names of three transcription factors, the pituitary-specific Pit-1, the octamer-binding proteins Oct-1 and Oct-2, and the neural Unc-86 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. 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

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 (IPR000327), while the C-terminal subunit is a homeobox domain (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 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.[9][10]

Examples

Human genes encoding proteins containing the POU domain include:

References

  1. ↑ 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.
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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/er.22.1.2. PMID 11159814.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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. PMC 556730. PMID 1628619.
  9. 1 2 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.
  10. 1 2 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.
  11. ↑ 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.

This article incorporates text from the public domain Pfam and InterPro IPR000327

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