What are Protein Domains?
Protein domains are the functional units within a protein that are responsible for the overall function of the protein. These domains are responsible for interacting with other cellular components such as other proteins. Similar protein domains can be found in different proteins with different functions. [1]
FOXE1
Protein Domain
The FOXE1 gene contains only one protein domain: the fork head domain (FH). This protein domain is most often found in transcriptional factors that are responsible for binding to DNA and promoting the transcription of DNA into RNA via RNA Polymerase II. [2]
The FH domain is located on the 51 to 141 position of the FOXE1 protein. Mutations in this region have shown to be associated with congenital hypothyrodism as well as thyroid dysgenesis. [3] |
Figure [2]. Structure of the fork head domain.
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Low Complexity Region
In addition to the FH domain, FOXE1 contains several low complexity regions (LCR). While the specific functions of many LCRs remain unclear, studies suggest that LCRs may play an important role in protein protein interactions and that their functions may be determined by their position within the protein sequence. [4]
Mutations in the LCR at position 248 of FOXE1 have shown to be associated with NMTC and an increased expression of the WNT5A gene: whose protein products have been associated with embryonic development and oncogenesis. [5] [6]
Mutations in the LCR at position 248 of FOXE1 have shown to be associated with NMTC and an increased expression of the WNT5A gene: whose protein products have been associated with embryonic development and oncogenesis. [5] [6]
FOXE1 Protein Domains in Homologs
Discussion
FOXE1 is highly conserved across mammalian species. Within these species, the overall length of the protein as well as the position of the fork head protein domain are also well conserved. As non-mammalian species have a < 60% percent identity, mammalian species should be used when studying the function of FOXE1 in a laboratory setting.
In addition, as mutations in the LCR of FOXE1 is associated with NMTC, LCRs may be a potential site of interest when studying FOXE1 association to NMTC.
In addition, as mutations in the LCR of FOXE1 is associated with NMTC, LCRs may be a potential site of interest when studying FOXE1 association to NMTC.
References
[1] “What Are Protein Domains?” AAA ATPase Domain (IPR003593) < InterPro < EMBL-EBI, 20 July 2016, https://www.ebi.ac.uk/training/online/course/introduction-protein-classification-ebi/protein-classification/what-are-protein-domains
[2] “Five Years on the Wings of Fork Head.” Egyptian Journal of Medical Human Genetics, Elsevier, 8 Mar. 1999, https://www.sciencedirect.com/science/article/pii/0925477396005394?via%3Dihub
[3] Kang, IN., Musa, M., Harun, F. et al. Biochem Genet (2010) 48: 141. https://doi.org/10.1007/s10528-009-9306-7
[4] Coletta, Alain, et al. “Low-Complexity Regions within Protein Sequences Have Position-Dependent Roles.” BMC Systems Biology, vol. 4, no. 1, 2010, p. 43., doi:10.1186/1752-0509-4-43.
[5] Pereira, J.S., da Silva, J.G., Tomaz, R.A. et al. Endocrine (2015) 49: 204. https://doi.org/10.1007/s12020-014-0470-0
[6] Bhatt PM, Malgor R (November 2014). "Wnt5a: a player in the pathogenesis of atherosclerosis and other inflammatory disorders". Atherosclerosis. 237 (1): 155–62. doi:10.1016/j.atherosclerosis.2014.08.027
[1] “What Are Protein Domains?” AAA ATPase Domain (IPR003593) < InterPro < EMBL-EBI, 20 July 2016, https://www.ebi.ac.uk/training/online/course/introduction-protein-classification-ebi/protein-classification/what-are-protein-domains
[2] “Five Years on the Wings of Fork Head.” Egyptian Journal of Medical Human Genetics, Elsevier, 8 Mar. 1999, https://www.sciencedirect.com/science/article/pii/0925477396005394?via%3Dihub
[3] Kang, IN., Musa, M., Harun, F. et al. Biochem Genet (2010) 48: 141. https://doi.org/10.1007/s10528-009-9306-7
[4] Coletta, Alain, et al. “Low-Complexity Regions within Protein Sequences Have Position-Dependent Roles.” BMC Systems Biology, vol. 4, no. 1, 2010, p. 43., doi:10.1186/1752-0509-4-43.
[5] Pereira, J.S., da Silva, J.G., Tomaz, R.A. et al. Endocrine (2015) 49: 204. https://doi.org/10.1007/s12020-014-0470-0
[6] Bhatt PM, Malgor R (November 2014). "Wnt5a: a player in the pathogenesis of atherosclerosis and other inflammatory disorders". Atherosclerosis. 237 (1): 155–62. doi:10.1016/j.atherosclerosis.2014.08.027
Image References
[1] https://upload.wikimedia.org/wikipedia/commons/thumb/c/c0/1mwp_gfld.png/1200px-1mwp_gfld.png
[1] https://upload.wikimedia.org/wikipedia/commons/thumb/c/c0/1mwp_gfld.png/1200px-1mwp_gfld.png