This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison.
Pfam
From Pfam, 2011. Retrieved from http://pfam.sanger.ac.uk/search/sequence/results/edb5b480-df3a-4cdb-bce7-cd788344c98e
SMART
SMART found a coiled-coil domain at amino acid position 111-184 as well as an OLF (Olfactomedin-like) domain from 284-503. The OLF domain has an e-value of 2.11xe^-149.
Description of Domains:
Both Pfam and Smart recognized and OLF domain which spans from amino acid 284 to 503 in the 504 amino acid sequence. The Olf domain is an Olfactomedin domain which SMART recognizes as first identified in olfactomedin, an extracellular matrix protein of the olfactory neuroepithelium. This type of domain is seen in many metazoan proteins, including myocilins, neolins, and optimedins. Often, it is mutations in this Olf domain that lead to glaucoma. The Olf domain is of particular importance for myocilin as it allows for interaction with another protein, optimedin, via its Olf domain as well.
While Pfam does not recognize a coiled coil region in the myocilin protein, SMART does recognize this structural motif. It is recognized to span from amino acid 111 to 184. This coiled coil region in myocilin is of unknown function and is likely insignificant as it was only recognized by one of the databases. However, coiled coil regions are often involved in regulating gene expression so further analysis of this domain is necessary for any certain conclusions.
Both Pfam and Smart recognized and OLF domain which spans from amino acid 284 to 503 in the 504 amino acid sequence. The Olf domain is an Olfactomedin domain which SMART recognizes as first identified in olfactomedin, an extracellular matrix protein of the olfactory neuroepithelium. This type of domain is seen in many metazoan proteins, including myocilins, neolins, and optimedins. Often, it is mutations in this Olf domain that lead to glaucoma. The Olf domain is of particular importance for myocilin as it allows for interaction with another protein, optimedin, via its Olf domain as well.
While Pfam does not recognize a coiled coil region in the myocilin protein, SMART does recognize this structural motif. It is recognized to span from amino acid 111 to 184. This coiled coil region in myocilin is of unknown function and is likely insignificant as it was only recognized by one of the databases. However, coiled coil regions are often involved in regulating gene expression so further analysis of this domain is necessary for any certain conclusions.
Analysis: It is interesting that Pfam did not recognize the coiled-coil domain at amino acid position 111-184 as the SMART output did; however, it is encouraging that both methods of analysis agreed on the OLF domain starting at amino acid 284 of the 504 amino acid sequence. Further analysis and refinement of analysis/output options may allow for additional agreement between Pfam and SMART.
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References:
1. Fuse, Nobuo. "Genetic Bases for Glaucoma." The Tohoku Journal of Experimental Medicine 221 (2010): 1-10. PubMed. Web. 22 Jan. 2011
http://www.jstage.jst.go.jp/article/tjem/221/1/1/_pdf
2. Rao, Kollu N., Srujana Nagireddy, and Subhabrata Chakrabarti. "Complex Genetic Mechanisms in Glaucoma: An Overview." Indian Journal of Opthamology 59.7 (2011): 31-42. PubMed. Web. 22 Jan. 2011.
http://www.ijo.in/article.asp?issn=0301-4738;year=2011;volume=59;issue=7;spage=31;epage=42;aulast=Rao
3. American Optometric Association. Answers To Your Questions About Glaucoma. St. Louis: American Optometric Association. Print.
4. http://www.forbes.com/2009/06/26/life-saving-devices-technology-personal-monitors_slide_7.html
5. http://www.youtube.com/watch?v=OJMEfGFbFMI
6. "MYOC - Myocilin, Trabecular Meshwork Inducible Glucocorticoid Response - Genetics Home Reference." Genetics Home Reference - Your Guide to Understanding Genetic Conditions. 6 Feb. 2011. Web. 08 Feb. 2011. http://ghr.nlm.nih.gov/gene/MYOC
7. Saura, Maria, Montse Cabana, Carmen Ayuso, and Diana Valverde. "European Journal of Human Genetics - Mutations including the Promoter Region of Myocilin//TIGR Gene." Nature Publishing Group : Science Journals, Jobs, and Information. 13 Oct. 2004. Web. 08 Feb. 2011. http://www.nature.com/ejhg/journal/v13/n3/full/5201299a.html
8. Fingert, John H., Elise Heon, Jefferey M. Liebmann, Tetsuya Yamamoto, Jaime E. Craig, Julian Rait, Kazuhide Kawase, Sek-Tien Hoh, Yvonne M. Buys, Joanne Dickinson, Robin R. Hockey, Donna Williams-Lyn, Graham Trope, Yoshiaki Kitazawa, Robert Ritch, David A. Mackey, Wallace L.M. Alward, Val C. Sheffield, and Edwin M. Stoned. "Analysis of Myocilin Mutations in 1703 Glaucoma Patients From Five Different Populations — Hum Mol Genet." Oxford Journals | Life Sciences & Medicine | Human Molecular Genetics. 14 Mar. 1999. Web. 08 Feb. 2011. http://hmg.oxfordjournals.org/content/8/5/899.full
9. McMahon, C., Semina, E.V., Link, B.A. "Using zebrafish to study the complex genetics of glaucoma." Comparative Biochemistry and Physiology Part C: Toxicology and Parmacology. vol 138-3. July 2004. Web. 24 Feb 2011. http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6W89-4CDJG6X-1&_user=443835&_coverDate=07%2F31%2F2004&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_acct=C000020958&_version=1&_urlVersion=0&_userid=443835&md5=525db1a96bf7be7620dabbcd34c426f9&search#toc2
10. Kubota, R., Noda, S., Wang, Y., Minoshima, S., Asakawa, S., Kudoh, J., Mashima, Y., Oguchi, Y., Shimizu, N. "A novel myosin-like protein (myocilin) expressed in the connecting cilium of the photoreceptor: molecular cloning, tissue expression, and chromosomal mapping." Genomics. vol 41-3.1 May 1997, Pages 360-369 Department of Molecular Biology, Keio University School of Medicine, Tokyo, Japan. http://www.sciencedirect.com.ezproxy.library.wisc.edu/science?_ob=ArticleURL&_udi=B6WG1-45M8YTG-C5&_user=443835&_coverDate=05%2F01%2F1997&_rdoc=1&_fmt=high&_orig=gateway&_origin=gateway&_sort=d&_docanchor=&view=c&_acct=C000020958&_version=1&_urlVersion=0&_userid=443835&md5=1562ae0f98031b9d89c1c8377a859b1e&search
References:
1. Fuse, Nobuo. "Genetic Bases for Glaucoma." The Tohoku Journal of Experimental Medicine 221 (2010): 1-10. PubMed. Web. 22 Jan. 2011
http://www.jstage.jst.go.jp/article/tjem/221/1/1/_pdf
2. Rao, Kollu N., Srujana Nagireddy, and Subhabrata Chakrabarti. "Complex Genetic Mechanisms in Glaucoma: An Overview." Indian Journal of Opthamology 59.7 (2011): 31-42. PubMed. Web. 22 Jan. 2011.
http://www.ijo.in/article.asp?issn=0301-4738;year=2011;volume=59;issue=7;spage=31;epage=42;aulast=Rao
3. American Optometric Association. Answers To Your Questions About Glaucoma. St. Louis: American Optometric Association. Print.
4. http://www.forbes.com/2009/06/26/life-saving-devices-technology-personal-monitors_slide_7.html
5. http://www.youtube.com/watch?v=OJMEfGFbFMI
6. "MYOC - Myocilin, Trabecular Meshwork Inducible Glucocorticoid Response - Genetics Home Reference." Genetics Home Reference - Your Guide to Understanding Genetic Conditions. 6 Feb. 2011. Web. 08 Feb. 2011. http://ghr.nlm.nih.gov/gene/MYOC
7. Saura, Maria, Montse Cabana, Carmen Ayuso, and Diana Valverde. "European Journal of Human Genetics - Mutations including the Promoter Region of Myocilin//TIGR Gene." Nature Publishing Group : Science Journals, Jobs, and Information. 13 Oct. 2004. Web. 08 Feb. 2011. http://www.nature.com/ejhg/journal/v13/n3/full/5201299a.html
8. Fingert, John H., Elise Heon, Jefferey M. Liebmann, Tetsuya Yamamoto, Jaime E. Craig, Julian Rait, Kazuhide Kawase, Sek-Tien Hoh, Yvonne M. Buys, Joanne Dickinson, Robin R. Hockey, Donna Williams-Lyn, Graham Trope, Yoshiaki Kitazawa, Robert Ritch, David A. Mackey, Wallace L.M. Alward, Val C. Sheffield, and Edwin M. Stoned. "Analysis of Myocilin Mutations in 1703 Glaucoma Patients From Five Different Populations — Hum Mol Genet." Oxford Journals | Life Sciences & Medicine | Human Molecular Genetics. 14 Mar. 1999. Web. 08 Feb. 2011. http://hmg.oxfordjournals.org/content/8/5/899.full
9. McMahon, C., Semina, E.V., Link, B.A. "Using zebrafish to study the complex genetics of glaucoma." Comparative Biochemistry and Physiology Part C: Toxicology and Parmacology. vol 138-3. July 2004. Web. 24 Feb 2011. http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6W89-4CDJG6X-1&_user=443835&_coverDate=07%2F31%2F2004&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_acct=C000020958&_version=1&_urlVersion=0&_userid=443835&md5=525db1a96bf7be7620dabbcd34c426f9&search#toc2
10. Kubota, R., Noda, S., Wang, Y., Minoshima, S., Asakawa, S., Kudoh, J., Mashima, Y., Oguchi, Y., Shimizu, N. "A novel myosin-like protein (myocilin) expressed in the connecting cilium of the photoreceptor: molecular cloning, tissue expression, and chromosomal mapping." Genomics. vol 41-3.1 May 1997, Pages 360-369 Department of Molecular Biology, Keio University School of Medicine, Tokyo, Japan. http://www.sciencedirect.com.ezproxy.library.wisc.edu/science?_ob=ArticleURL&_udi=B6WG1-45M8YTG-C5&_user=443835&_coverDate=05%2F01%2F1997&_rdoc=1&_fmt=high&_orig=gateway&_origin=gateway&_sort=d&_docanchor=&view=c&_acct=C000020958&_version=1&_urlVersion=0&_userid=443835&md5=1562ae0f98031b9d89c1c8377a859b1e&search
