This web page was produced as an assignment for Genetics 564, an undergraduate course at UW-Madison
Gene Ontology
The Gene Ontology Project (GO) was developed in 1999 to provide a database of the different aspects of genes that are being actively discovered. It is consistently updated to include the most recent research, and can be used to determine the descriptions of genes as they have been noted in scientific papers [1]. These descriptions are broken down into biological processes, molecular functions, and cellular components by the Protein Analysis Through Evolutionary Relationships (PANTHER) Classification System [2].
Analysis
On the Gene Ontology Consortium homepage there is a search option for Enrichment Analysis. For the purposes of this analysis, the Slc6a4 protein in Rattus norvegius was chosen and biological processes picked for the initial Term Enrichment. The GO database AmiGO compiled a list of all the results, as they were produced by PANTHER.
This process was repeated for both molecular function and cellular components and those results that were most clearly connected to the SLC6A4 gene are displayed below.
Biological Processes
|
Molecular Function
|
Cellular Components
|
Serotonin Transport (GO:0006837)
Monoamine Transport (GO:0015844) Serotonin Uptake (GO:0051610) Brain Development (GO:0007420) Circadian Rhythm (GO:0007623) Memory (GO:0007613) Negative Regulation of Neuron Differentiation (GO:0045665) Response to Drug (GO:0042493) |
Serotonin:sodium Symporter Activity (GO:0005335)
Serotonin Transmembrane Transporter Activity (GO:0015222) Cocaine Binding (GO:0019811) |
Cytosol (GO:0005829)
Plasma Membrane (GO:0005886) Synaptosome (GO:0019717) |
Discussion
Results for GO terms corresponding to SLC6A4 were very much as expected based on the known functions of the protein. The cellular components are all classic indicators of a transmembrane protein since they associated with the plasma membrane and cytosol, and knowing SLC6A4 to be a component of neurotransmitter reuptake the connection to the synaptosome is also clear [3]. The functions that have been discussed in the literature are also represented in the list of molecular functions. SLC6A4 is primarily involved in the binding and reuptake of serotonin through the pre-synpatic neural membrane [3]. Certain drugs are also known to affect serotonin levels and its uptake, including cocaine [4]. The biological processes group was by far the largest, but the terms listed are still representative of the known processes linked to SLC6A4. The transport and uptake of the monoamine serotonin is the main purpose of this protein, and when that is disrupted there are many secondary processes that can be affected. Low serotonin levels have been linked to depression. Several symptoms of depression include insomnia, involving the circadian rhythm, as well as memory loss, which can employ loss of neuron differentiation and affects brain development [5]. Certain drugs, including cocaine, are able to interfere by binding SLC6A4 and blocking reuptake, causing elevated levels of serotonin and leading to the trademark hyperactivity seen with cocaine use [4].
References
Gene Ontology Consortium: http://geneontology.org/
[1] About the Gene Ontology Project. (n.d.). Retrieved March 21, 2015, from http://geneontology.org/page/about
[2] About Panther. (n.d.). Retrieved March 21, 2015, from http://go.pantherdb.org/about.jsp
[3] Lesch, K., Balling, U., Gross, J., Strauss, K., Wolozin, B., Murphy, D., & Riederer, P. (1994). Organization of the human serotonin transporter gene. Journal of Neural Transmission, 95(2), 157-162. Retrieved February 18, 2015, from http://link.springer.com.ezproxy.library.wisc.edu/article/10.1007/BF01276434
[4] Bardi, J. (2003, September 1). Serotonin Receptors and Drug Abuse. Retrieved March 21, 2015, from https://www.scripps.edu/newsandviews/e_20030929/parsons.html
[5] Symptoms of Depression. (n.d.). Retrieved March 21, 2015, from http://www.webmd.com/depression/guide/detecting-depression
[1] About the Gene Ontology Project. (n.d.). Retrieved March 21, 2015, from http://geneontology.org/page/about
[2] About Panther. (n.d.). Retrieved March 21, 2015, from http://go.pantherdb.org/about.jsp
[3] Lesch, K., Balling, U., Gross, J., Strauss, K., Wolozin, B., Murphy, D., & Riederer, P. (1994). Organization of the human serotonin transporter gene. Journal of Neural Transmission, 95(2), 157-162. Retrieved February 18, 2015, from http://link.springer.com.ezproxy.library.wisc.edu/article/10.1007/BF01276434
[4] Bardi, J. (2003, September 1). Serotonin Receptors and Drug Abuse. Retrieved March 21, 2015, from https://www.scripps.edu/newsandviews/e_20030929/parsons.html
[5] Symptoms of Depression. (n.d.). Retrieved March 21, 2015, from http://www.webmd.com/depression/guide/detecting-depression