This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison.
What is gene ontology?
Gene ontologies (GO) are a set of vocabularies for defined terms representing gene product function. These terms fall under three domains: Cellular Component, Molecular Function, and Biological Process. Most importantly, these terms were created to be species-agnostic, or all terms should be applicable to all life, from prokaryotes to eukaryotes and from single-cell life to multicellular life.
Cellular Component is a portion of a cell that is part of a larger object, for example an anatomical structure (e.g. rough endoplasmic reticulum or Golgi apparatus) or a gene product group (e.g. ribosome, proteasome or a protein dimer).
Molecular Function describes a series of actions carried out by one or more organized assemblies of molecular functions (e.g. metal ion binding or signal transduction).
Biological Process describes activities of a single gene product that occurs at the molecular level, such as "catalytic activity" or "metabolic process".
Cellular Component is a portion of a cell that is part of a larger object, for example an anatomical structure (e.g. rough endoplasmic reticulum or Golgi apparatus) or a gene product group (e.g. ribosome, proteasome or a protein dimer).
Molecular Function describes a series of actions carried out by one or more organized assemblies of molecular functions (e.g. metal ion binding or signal transduction).
Biological Process describes activities of a single gene product that occurs at the molecular level, such as "catalytic activity" or "metabolic process".
What are the GO terms of the Human GALT gene
Cellular Components
The Human GALT is annotated as being active in the Golgi apparatus and the cytosol. The cytosol is the aqueous (water) portion of the cytoplasm of a cell, within which various protein complexes and organelles reside (GO:0005829). This is expected since it is where glycolysis occurs, a process that galactose catabolism is directly tied to. The Golgi apparatus is an organelle of eukaryotes composed of ribosome-free vesicles (GO:0005794). It is involved in the processing of proteins, such as glycosylation, and the sorting and packaging of proteins for transport. It is reasonable that GALT would be active here sense both galactose and galactosamine are used in glycosylation processes, thus GALT may be critical in this process.
Molecular Functions
The Human GALT is annotated as having the molecular functions of protein binding (GO:0005515), UDP-glucose:hexose-1-phosphate uridylyltransferase activity (GO:0008108), and zinc ion binding (GO:0008270). Protein binding function is very broad and can involve protein degradation tagging activity, folding chaperone, and dimer formation. As already discussed, GALT is a UDP-glucose:hexose-1-phosphate uridylyltransferase and catalyzes the second step in the Leloir pathway and is annotated as such. Lastly, as discussed in the domains section Zinc is required for proper enzymatic function and as expected GALT is annotated as a Zinc binding enzyme.
Biological Processes
The Human GALT protein is annotated as a part of the galactose metabolic process, galactose catabolic process, and UDP-glucose catabolic process. These all are very obvious process, since GALT is the second enzyme of the Leloir pathway, which is the exchange of a UDP between galactose and glucose. Galactose metabolic process is the chemical reactions and pathways involving galactose, which is constituent of mono-, di-, oligo-, and polysaccharides and galactolipids. Galactose catabolic process is the reactions and pathways involved in the breakdown of galactose AKA the Leloir pathway. Finally, UDP-glucose catabolic process is the reactions and pathways resulting in the breakdown of UDP-glucose and uridinediphosphoglucose, the former of which is closely linked to the Leloir pathway.
Conclusions
GALT is annotated as expected as a enzyme involved in galactose metabolism, active in the cytoplasm and golgi apparatus, and involved in protein and zinc binding. However, a recent study revealed that a GALT is a positive regulator of the PI3K/Akt signaling pathway [1]. This suggest that the global role of GALT has yet to be fully elucidated, thus in doing so will greatly enhance our knowledge of how galactosemia causes later in life disease phenotypes.
References
1. Balakrishnan et al. Galactose-1 phosphate uridylyltransferase (GalT) gene: a novel positive regulator of the PI3K/Akt signaling pathway in mouse fibroblasts. Biochem Biophys Res Commun 2016;470:205-212