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Scansite searches for motifs within proteins that are likely to
be phosphorylated by specific protein kinases or bind to domains
such as SH2 domains, 14-3-3 domains or PDZ domains.
Optimal phosphorylation sites for particular protein Ser/Thr kinases
or protein-Tyr kinases are predicted using the matrix of selectivity
values for amino acids at each position relative to the phosphorylation
site as determined from the oriented peptide library technique
described by Songyang et al., 1994, Current Biology 4, 973-982
and Songyang et al., 1995, Nature 373, 536-539.
Optimal binding sites for SH2 domains, PDZ domains, 14-3-3 domains
and other domains are determined using the matrix of selectivity
values for amino acids at each position relative to an orienting
residue as determined by the oriented peptide library technique
described in Songyang et al., 1993 Cell 72, 767-778, Songyang et
al., 1997 Science 275, 73-77 and Yaffe et al., 1997 Cell 91, 961-971.
The same matrices of selectivity values are used in an approach
to provide relative scores of candidate motifs in protein sequences
evaluated. The Motifscanner program utilizes an entropy approach
that assesses the probability of a site matching the motif using
the selectivity values and sums the logs of the probability values
for each amino acid in the candidate sequence. The program then
indicates the percentile ranking of the candidate motif in respect
to all potential motifs in proteins of a protein database. When
available, percentile scores of some confirmed phosphorylation
sites for the kinase of interests or confirmed binding sites of
the domain of interest are provided for comparison with the scores
of the candidate motifs.
In the graphical output, the candidate motifs are superimposed
on the predicted domain structure of the protein. Clicking on the
domain information button provides access to a hot link to the
domain families via Pfam. Clicking on the motif region provides
the primary sequence at the motif and the percentile score. The
program also provides information about the surface probability
of the region of the protein around the motif of interest.
References
[1] Songyang Z, Blechner S, Hoagland N, Hoekstra MF, Piwnica-Worms
H, Cantley LC, Use
of an oriented peptide library to determine the optimal substrates
of protein kinases , Curr Biol. 1994 Nov 1; 4(11): 973-82.
[2] Yaffe MB, Leparc GG, Lai J, Obata T, Volinia S, Cantley LC, A
motif-based profile scanning approach for genome-wide prediction
of signaling pathways , Nat Biotechnol. 2001 Apr; 19(4):
348-53.
[3] Obenauer JC, Cantley LC, Yaffe MB, Scansite
2.0: Proteome-wide prediction of cell signaling interactions
using short sequence motifs , Nucleic Acids Res. 2003 Jul
1; 31(13): 3635-41
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