This page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison.

Gene Ontology

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The Gene Ontology (GO) database describes proteins in a species independent manner in terms of their associated biological processes, cellular components and molecular functions using a controlled vocabulary (an ontology) (The Gene Ontology Consortium, 2000). In this database, molecular functions are defined as "the activities [of the protein], such as catalytic or binding activities, that occur at the molecular level", while biological processes are "series of events accomplished by one or more ordered assemblies of molecular functions" (The Gene Ontology Consortium, 2000). The database uses cellular components describe the location of the protein "at the [level] of subcellular structures and macromolecular complexes" (The Gene Ontology Consortium, 2000). To determine the gene ontology of GRM7, "grm7" was queried in a "genes or proteins" search on AmiGO, the official GO search engine (The Gene Ontology Consortium, 2000; Carbon, et al., 2008). Other search engines, including GOA and QuickGO were also used to determine the gene ontology of human GRM7; however, because these sites also search the GO database, they returned the same results as AmiGO.

As can be seen in Figure 1,
AmiGO returned two biological processes, three cellular components, and three molecular functions for human GRM7 (Carbon, et al., 2008). The involvement of human GRM7 in each of these  biological processes, cellular components, and molecular functions comes from traceable author statement (TAS) evidence, meaning that GRM7 was categorized based on author statements attributable a cited source, rather than on direct evidence (Carbon, et al., 2008)
. While direct evidence for the categorization of GRM7 under each of these eight terms is more desirable, traceable author statements are considered reliable, and therefore, these eight categorizations provide valuable insight into the biological roles of GRM7, as discussed below.

.Figure 1. Table of GO terms returned by AmiGO for human GRM7. The figure above shows a screenshot of the table returned by the AmiGO search engine for the human GRM7 protein. The first column gives the GO database accession number along with term under which human GRM7 is categorized (AmiGO). The far right of the first column gives links (which are inactive in this screenshot) to look at all the gene products under that particular term and to view the gene ontology tree for that particular term (AmiGO). The second column gives which of the three ontologies (biological process, cellular component, or molecular function) the term is found in (AmiGO). The third column, which gives qualifiers such as "NOT" or "co-localizes with" is blank for all the terms in this table, indicating that there are no flags that would modify the interpretation of  the categorization of GRM7 under these terms. The fourth column gives the source of evidence for the classification of human GRM7 under each term. In this case, GRM7 was classified under all of the terms in this table on the basis of traceable author statement (TAS) evidence, meaning that GRM7 was categorized based on author statements attributable a cited source, rather than on direct evidence (AmiGO).The fifth column gives a link to the reference used to make an association between that particular term and human GRM7 (AmiGO). Finally, the last column gives the group or database that assigned the association of human GRM7 to that term (AmiGO).

Molecular Functions

Human GRM7 is categorized under three molecular function terms in the GO database: G-protein coupled receptor activity, glutamate receptor activity, and PDZ domain binding (The Gene Ontology Consortium, 2000; Carbon, et al., 2008). Due to the GRM7 protein being a member of a family of G-protein coupled glutamate receptors, it is expected that GRM7 would be classified as having both G-protein coupled receptor activity and glutamate receptor activity (Carbon, et al., 2008; Okamoto, et al., 1994). A more interesting categorization of GRM7 its PDZ domain binding function, which indicates that GRM7 interacts with at least one intracellular signaling protein (Figure 2) (Carbon, et al., 2008). It may be through this PDZ domain that GRM7 propagates the signal it receives.

Cellular Components

Human GRM7 is categorized under three cellular component terms in the GO database: integral to plasma membrane, postsynaptic membrane, and presynaptic active zone membrane (The Gene Ontology Consortium, 2000; Carbon, et al., 2008). The location of GRM7 in the plasa membrane indicates that it is involved in cell-cell signaling, rather than just intracellular signaling (Carbon, et al., 2008). It is interesting that GRM7 is found on both the presynaptic and postsynaptic membranes, as this suggests that GRM7 plays a role in both sending and receiving glutamate signals (Carbon, et al., 2008).

Biological Processes

Human GRM7 is categorized under two biological process terms in the GO database: synaptic transmission and negative regulation of adenylate cyclase activity (The Gene Ontology Consortium, 2000; Carbon, et al., 2008). Graphical views of the ontologies for these two terms can be seen in Figures 3 and 4. Classification of GRM7 under synaptic transmission shows that GRM7 is involved in transmission of nerve impulses through cell-cell signaling (Carbon, et al., 2008). Knowing that GRM7 is a glutamate receptor, as well as in light of its other GO classifications, this might be expected. (Carbon, et al., 2008; Okamoto, et al., 1994) The categorization of GRM7 under negative regulation of adenylate cyclase activity provides a more novel insight into the role of GRM7, indicating that the receptor transmits the signal it recieves, at least in part, by decreasing adenylate cyclase activity (Carbon, et al., 2008).

Figure 2. Graphical view of PDZ domain binding. Red arrows represent "is a" connections (Carbon, et al., 2008). For example, PDZ domain binding is a protein domain specific binding function (Carbon, et al., 2008).

Figure 3. Graphical view synaptic transmission. Red arrows represent "is a" connections, while blue arrows represent "part of" connections (Carbon, et al., 2008). For example, synaptic transmission is a cell-cell signaling process, and is part of transmission of nerve impulses (Carbon, et al., 2008).

Figure 4. Graphical view negative regulation of adenylate cyclase activity. Red arrows represent "is a" connections, while maroon arrows represent "regulates" connections (Carbon, et al., 2008). For example, negative regulation of adenylate cyclase activity is a cell-cell signaling process (Carbon, et al., 2008).

References

References

 

Carbon, S., Ireland, A., Mungall, C.J., Shu, S., Marshall, B., Lewis, S.; the AmiGO Hub; the Web Presence Working Group. (2008). AmiGO: online access to ontology and annotation data. Bioinformatics. [epub ahead of print].

The Gene Ontology Consortium. (2000). Gene Ontology: tool for the unification of biology. Nature Genetics. 25(1):25-29. doi:10.1038/75556

Okamoto, N., Hori, S., Akazawa, C., Hayashi, Y., Shigemoto, R., Mizuno, M., and Nakanishi, S. (1994, January 14). Molecular characterization of a new metabotropic glutamate receptor mGluR7 coupled to inhibatory cyclic AMP signal transduction. [Abstract]. The Journal of Biological Chemistry, 269(2), 1231. Retrieved February 2, 2009, from http://www.ncbi.nlm.nih.gov/pubmed/8288585?dopt=Abstract

Jennifer Wagner
wagner4@wisc.edu
Updated March 28, 2009
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