This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison.
What are protein domains?
Protein domains are distinct functional and/or structural units of a protein.[1] Domains typically aid in particular functions or interactions for the protein, and the combination of all of the proteins domains, as well as other factors, gives the overall function of the protein. Similar proteins have similar domains, and this could be for multiple different reasons.[1] Two reasons could be homology and similar function. Homologous proteins may have similar domains because they're closely related, but even distantly related proteins may have similar domains because they're necessary to perform a certain function. Proteins with similar domains may be in the same protein family, suggesting similar sequences and even functions. [1]
Conserved domains on proteins help aide in the classification and organization of proteins into families. [1] Conserved domains, by nature, show minimal changes to their sequence over-time, most likely due to the importance of the sequence. These minimal changes caused by mutations over-time makes it much easier to analyze proteins within families and precisely categorize them, as well as it helps predict that the function of said domain will remain relatively constant. These conserved domains can sometimes also be the location of potentially protein-fatal mutations, as the domain is likely conserved because of its specificity and importance.
TMC Domain
Both TMC6 and TMC8 code for transmembrane protein channels and are in the transmembrane channel-like proteins (TMC) family. This family includes TMC1 through TMC8, as well as other transmembrane proteins. [2] An important characteristic of this family is its highly conserved TMC domain seen in all of them.
TMC6 Protein Domains
Results: Both tools showed the conserved TMC region, but SMART also shows the transmembrane domains (blue) and low-complexity regions (pink) that are contained within TMC6.
TMC8 and Mouse TMC6
Although TMC6 and TMC8 are not exactly identical and do not perform the exact same functions in the cell, the basic sequence is very similar in both genes. The main components that the two share are transmembrane domains (blue) and the TMC domain. This is the same with the mouse TMC6 as well. These domains most likely combine to give rise to the similar functions between the two proteins.
Conclusion
TMC6's function as an integral transmembrane channel can easily be justified by the transmembrane and TMC domain. The fact that TMC is highly conserved in both human TMC-family proteins and mouse suggest that is integral to the function of the protein. Mouse-TMC6 shows high homology with human-TMC6, and this suggests that TMC6 has been a conserved protein from at least the divergence of mouse and human's last common ancestor. This also suggest that human and mouse TMC6 may perform similar functions.
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Sources:
1. https://www.ebi.ac.uk/training/online/course/introduction-protein-classification-ebi/protein-classification/family-and-domain-based-protei
2. http://smart.embl-heidelberg.de/smart/job_status.pl?jobid=681851719575811552547341ooCjhrwcfK
Figure: https://www.google.com/url?sa=i&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwjw5tjKh4HhAhUd3YMKHR5tBo0Qjhx6BAgBEAM&url=https%3A%2F%2Fen.wikipedia.org%2Fwiki%2FProtein_domain&psig=AOv Vaw3KCQCijDP3asoLdcRtW_YS&ust=1552633007599005
1. https://www.ebi.ac.uk/training/online/course/introduction-protein-classification-ebi/protein-classification/family-and-domain-based-protei
2. http://smart.embl-heidelberg.de/smart/job_status.pl?jobid=681851719575811552547341ooCjhrwcfK
Figure: https://www.google.com/url?sa=i&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwjw5tjKh4HhAhUd3YMKHR5tBo0Qjhx6BAgBEAM&url=https%3A%2F%2Fen.wikipedia.org%2Fwiki%2FProtein_domain&psig=AOv Vaw3KCQCijDP3asoLdcRtW_YS&ust=1552633007599005