This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison Spring 2009
Protein Domains of SORL1 Homologs
As you look at the protein domains of SORL1 homologs in (from top to bottom) Mouse, Rat, Dog, Chicken, and Cow, the high degree of similarity is immediately obvious. With the exception of the Rat homolog, the protein domains are nearly identical to each other and with Human SORL1. Each contains a VPS10 domain, which characterizes the class of proteins that were initially investigated by Rogaeva et. al. when the link between SORL1 and Alzheimer's Disease was discovered. The homologs also share a variety of low-density lipoprotein receptor domains and fibronectin type 3 domains. The lone exception to this is of course the Rat, which has four transmembrane domains instead of the low-density lipoprotein-receptor YWTD domain.
The high degree of similarity amongst homologs makes each of these species suitable as model organisms. I would avoid using the Rat model because of the minor domain variability and the fact that the mouse model is available and nearly identical to Human SORL1. However, the ultimate insight into Alzheimer's and SORL1 will likely come from studies to understand the control of gene expression, which has been shown to be the link the AD.
References
SMART Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864 and Letunic et al. (2008) Nucleic Acids Res , doi:10.1093/nar/gkn808
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Last Updated 5/13/09
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