Protein Domain

This web page was produced as an assignment for Gen677 at UW-Madison Spring 2009

Prosite protein domains

Through my search on PROSITE (2), with the mouse version of SIRT6 I found one major domain that domain is known as SIRTUIN domain.  The description of this domains function is that it performs a new type of chemical reaction where the enzyme requires NAD+ which then allows the enzyme to deacetylase a peptide (Sauve, et al 2001).  This reaction then gives rise to a deacetylated peptide and acetyl ADP-ribose, the acetyl ADP-ribose molecule as of now has no know function in the cell. The sirtuin domain also has other key structural features like a rossman fold and a zinc binding domain that consists of cysteine residues that help to coordinate zinc ions ( Dutnail, et al 2001).

Pfam Protien domains

This is an image SIR2 bound to the P53 peptide with nicotinamide bound

I also did a sequence scan with the Pfam (1) website to see if other websites would give me more domain results for SIRT6.  I again only got a match for the SIR2 domain but with Pfam I was able to get an actual number of how specific this match, which I got a E value of 1.4e-13. 

Possible reasons for phenotypes

From what I have learned about the Sirtuin domains function it seem that SIRT6 deacetylates proteins or histones.  So this leads me to believe that if SIRT6 is lost it could cause either protein or histones that would usually be deacetylated not to be.  This could lead to a few possibilities for example if deacetylation of a protein is meant to inhibit it then that protein would not be inhibited any more and could lead to uncontrolled activity of that protein.  Or SIRT6 could deacetylate histones thus silencing genes.  So when SIRT6 is knocked out I would expect uncontrolled activity of proteins or certain genes

References

1. R.D. Finn, J. Tate, J. Mistry, P.C. Coggill, J.S. Sammut, H.R. Hotz, G. Ceric, K. Forslund, S.R. Eddy, E.L. Sonnhammer and A. Bateman Nucleic Acids Research (2008)  Database Issue 36:D281-D288

2. Hulo N., Bairoch A., Bulliard V., Cerutti L., Cuche B., De Castro E., Lachaize C., Langendijk-Genevaux P.S., Sigrist C.J.A.The 20 years of PROSITE.Nucleic Acids Res. 2007 Nov 14.PubMed: 18003654/

Mark Devries
Email [email protected]
last updated 1/22/09
http://www.gen677.weebly.com