http://www.uniprot.org/uniprot/P10721#showFeaturesViewer).
In this mode, the features are grouped under certain blocks (e.g.,
“Domain & sites”), which corresponds to the sections in the main
UniProt protein pages. Clicking on the titles of these blocks will
reveal a more detailed view with subheadings. A snapshot from
“feature viewer” for human KIT protein is shown in Fig.2.(a) Clicking on “Domains & sites” will show functional domains,
regions and motifs; along with residue specific features. The
viewer displays the position of a feature on the protein
sequence by placing boxes/nodes at different positions along
the horizontal axis. Clicking on a box will reveal a new table,
showing the properties of that feature.
(b) Clicking on “Mutagenesis” will show the site specific muta-
tion information. This title will only be visible if there is
mutation information for that protein in the literature that is
recorded in UniProt. When any mutation locating box is
clicked, the opened table will display the description, mutation
states and the evidence containing the relevant literature
publications.
(c) Finally, clicking “Variants” will show detailed site-specific var-
iation information, obtained from the literature and from
other biological data resources. Position indicating circles are
colored according to the quality of the variation (i.e., disease,äFig. 2(continued) half-circles at each direction. At the top left, there are buttons for downloading the
displayed information in different formats, highlighting a selected region on the sequence, resetting the
view to the default and for zooming-in and out. Each horizontal block on the tool interface displays a specific
type of protein feature. Each block is a drop down menu that displays the sub-features upon clicking on the
name of the main feature (e.g., clicking on “Domains & sites” block reveals domain, region, active site, metal
binding, binding site, etc.). In order to indicate the exact position of a feature on the sequence, a colored node
is placed at the corresponding position on the horizontal axis. The color, shape, and width of the node/box is
respective to the type and the length of the feature (i.e., site-based features span only one residue; however,
region-based features such as domains may span hundreds of residues). For example, there is an active site
at the 792nd position of the KIT protein sequence. Clicking on the node of a feature will display two properties:
(1) a yellow vertical line will highlight that position along all of the feature blocks (e.g., the line shown in the
figure), which enables the observation of the correspondence between different types of features on the
sequence, and (2) a table displaying the details of the corresponding feature annotation such as the
description, the source of information and etc. At the bottom of the feature viewer, information about variants
is shown. The detailed view of variants block displays 20 different amino acids on the vertical axis, which
indicates the substituted amino acid at a specific position in the corresponding protein. The circular nodes that
indicate variations are colored according to the known or predicted effect of the variation (e.g., red for known
disease causing variants, different shades of blue for predicted deleterious effects, green for known
nondisease association, and yellow for initiation, stop loss or gain). For example, for the human KIT protein,
it has been recorded that a recorded variant has a glycine instead of an aspartic acid at the 52nd position. The
source of this information is the COSMIC database, the tissue of this sample is the large-intestine and the
effect of this variation was predicted to be mostly benign
Phylogenetics-Based Prediction of Functional Sites 57