POU domain

Last updated
Pou domain - N-terminal to homeobox domain
Identifiers
SymbolPou
Pfam PF00157
InterPro IPR000327
PROSITE PDOC00035
SCOP2 1oct / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

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.

Contents

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 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 (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

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

Related Research Articles

<span class="mw-page-title-main">Transcription factor</span> Protein that regulates the rate of DNA transcription

In molecular biology, a transcription factor (TF) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The function of TFs is to regulate—turn on and off—genes in order to make sure that they are expressed in the desired cells at the right time and in the right amount throughout the life of the cell and the organism. Groups of TFs function in a coordinated fashion to direct cell division, cell growth, and cell death throughout life; cell migration and organization during embryonic development; and intermittently in response to signals from outside the cell, such as a hormone. There are 1500-1600 TFs in the human genome. Transcription factors are members of the proteome as well as regulome.

<span class="mw-page-title-main">Homeobox</span> DNA pattern affecting anatomy development

A homeobox is a DNA sequence, around 180 base pairs long, that regulates large-scale anatomical features in the early stages of embryonic development. Mutations in a homeobox may change large-scale anatomical features of the full-grown organism.

<span class="mw-page-title-main">Oct-4</span> Mammalian protein found in Homo sapiens

Oct-4, also known as POU5F1, is a protein that in humans is encoded by the POU5F1 gene. Oct-4 is a homeodomain transcription factor of the POU family. It is critically involved in the self-renewal of undifferentiated embryonic stem cells. As such, it is frequently used as a marker for undifferentiated cells. Oct-4 expression must be closely regulated; too much or too little will cause differentiation of the cells.

A DNA-binding domain (DBD) is an independently folded protein domain that contains at least one structural motif that recognizes double- or single-stranded DNA. A DBD can recognize a specific DNA sequence or have a general affinity to DNA. Some DNA-binding domains may also include nucleic acids in their folded structure.

<span class="mw-page-title-main">Pituitary-specific positive transcription factor 1</span> Protein that controls rate of transcription of GH genes

POU domain, class 1, transcription factor 1 , also known as POU1F1, is a transcription factor for growth hormone.

Octamer transcription factors are a family of transcription factors which binds to the "ATTTGCAT" DNA sequence. Their DNA-binding domain is a POU domain.

Oct-2 also known as POU domain, class 2, transcription factor 2 is a protein that in humans is encoded by the POU2F2 gene.

<span class="mw-page-title-main">HMGA1</span> Protein-coding gene in the species Homo sapiens

High-mobility group protein HMG-I/HMG-Y is a protein that in humans is encoded by the HMGA1 gene.

<span class="mw-page-title-main">POU2F1</span> Protein-coding gene in the species Homo sapiens

POU domain, class 2, transcription factor 1 is a protein that in humans is encoded by the POU2F1 gene.

<span class="mw-page-title-main">HMGB2</span> Protein-coding gene in the species Homo sapiens

High-mobility group protein B2 also known as high-mobility group protein 2 (HMG-2) is a protein that in humans is encoded by the HMGB2 gene.

<span class="mw-page-title-main">POU2AF1</span> Protein-coding gene in the species Homo sapiens

POU domain class 2-associating factor 1 is a protein that in humans is encoded by the POU2AF1 gene. The protein is also termed Oct coactivator from B cells, Oct binding factor 1, and, as commonly found in the literature, BOB1. BOB1 is a transcriptional coactivator which is expressed principally by B-cell lymphocytes and controls immunoglobulin and other genes critical for these cells expression of CD20, CRISP-3, and CD36. The expression of BOB1 has proven useful for identifying certain lymphomas as being B-cell lymphomas, as exemplified in studies which use BAB1 expression to help identify lymphomas as being diffuse large B-cell lymphomas, not otherwise specified.

<span class="mw-page-title-main">SLC22A1</span> Protein-coding gene in the species Homo sapiens

Solute carrier family 22 member 1 is a protein that in humans is encoded by the gene SLC22A1.

<span class="mw-page-title-main">POU3F2</span> Protein-coding gene in the species Homo sapiens

POU domain, class 3, transcription factor 2 is a protein that in humans is encoded by the POU3F2 gene.

<span class="mw-page-title-main">POU4F1</span> Protein-coding gene in the species Homo sapiens

POU domain, class 4, transcription factor 1 (POU4F1) also known as brain-specific homeobox/POU domain protein 3A (BRN3A), homeobox/POU domain protein RDC-1 or Oct-T1 is a protein that in humans is encoded by the POU4F1 gene.

<span class="mw-page-title-main">POU3F1</span> Protein-coding gene in the species Homo sapiens

POU domain, class 3, transcription factor 1 is a protein that in humans is encoded by the POU3F1 gene.

<span class="mw-page-title-main">POU2F3</span> Protein-coding gene in the species Homo sapiens

POU domain, class 2, transcription factor 3 is a protein that in humans is encoded by the POU2F3 gene.

<span class="mw-page-title-main">Rel homology domain</span> Protein domain

The Rel homology domain (RHD) is a protein domain found in a family of eukaryotic transcription factors, including both NF-κB and NFAT, among others. Some of these transcription factors appear to form multi-protein DNA-bound complexes. Phosphorylation of the RHD appears to play a role in the regulation of some of these transcription factors, acting to modulate the expression of their target genes.

<span class="mw-page-title-main">Fork head domain</span> DNA-binding protein domain found in transcription factors

The fork head domain is a type of protein domain that is often found in transcription factors and whose purpose is to bind DNA.

<span class="mw-page-title-main">TBP-associated factor</span> Protein domains

The TBP-associated factors (TAF) are proteins that associate with the TATA-binding protein in transcription initiation. It is a part of the transcription initiation factor TFIID multimeric protein complex. It also makes up many other factors, including SL1. They mediate the formation of the transcription preinitiation complex, a step preceding transcription of DNA to RNA by RNA polymerase II.

<span class="mw-page-title-main">PKNOX2</span> Protein-coding gene in the species Homo sapiens

PBX/Knotted 1 Homeobox 2 (PKNOX2) protein belongs to the three amino acid loop extension (TALE) class of homeodomain proteins, and is encoded by PKNOX2 gene in humans. The protein regulates the transcription of other genes and affects anatomical development.

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. S2CID   24276357.
  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/edrv.22.1.0421 . 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. S2CID   9315961.
  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. doi:10.1002/j.1460-2075.1992.tb05320.x. 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. S2CID   36371069.
  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.
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