iProteinDB is an online protein database and resource tool for providing information
on post-translational modifications (PTMs) in Drosophila species. The data
of 6 Drosophila species was generated in the Perrimon lab, integrated with
other high-throughput data sets from three studies[1, 2, 3] and annotation
from UniProt and PhosphoSitePlus.
Users can query Drosophila genes of interest, and choose one isoform if there
are multiple non-redundant isoforms for the gene of interest. There are three tabs
from which to choose:
- Protein Details
A user can view the protein sequence from any of the 6 Drosophila species
in FASTA format. PTM sites are color-coded; the amino acid is displayed in red if
the PTM is observed, or blue if it was not observed but is predicted to be
phosphorylated based on the data from different Drosophila species. The
amino acid is underlined if the phosphorylation event was observed in more than
one Drosophila species. Protein domains are highlighted in green. A table
summarizing all the PTM sites for a given protein, as well as the data sources from
which the PTM information was extracted, is provided, along with detailed information
from the original sources, i.e. the original scores and peptide sequences. A table
summarizing all predicted sites based on data from closely-related Drosophila
species is provided with a link to detailed information and multiple sequence
alignments. Also indicated in this tab are sub-cellular localization annotation
from UniProt for each phosphoprotein and kinase predicted to act on individual
sites, as identified using ScanSite3.
- Predicted Orthologs
A user can find a table of the best ortholog candidates for major model organisms
based on DIOPT ortholog prediction. Mulitple sequence alignments
were performed based on the protein sequences of orthologous genes. The sequences
of all aligned Drosophila phosphosites, over a sliding window of five
residues, were compared to the corresponding sequences of each orthologous gene
and a similarity score was calculated by pairwise comparison. For example, if
10 or the 11 amino acids (phosphorylation site plus five amino acids upstream
and downstream) are identical between Drosophila and human sites, the
similarity score was assigned as 0.9 (10 divided by 11). Then, an average
similarity score was calculated based on all pairwise combinations at a given
site. All phosphorylation sites with an average similarity score of >0.5 are
listed and summarized as "conserved sites." Human disease-related variants
annotated at UniProt are also listed, along with sub-cellular localization annotation
of all orthologous proteins from UniProt. Multiple sequence alignment (MSA)
across major model organisms is displayed. For MSAs, observed PTM sites for all
orthologous genes are color-coded, domains are highlighted, and disease variants
are underlined. Conserved sites are bolded. As we hope that iProteinDB will lead
to new discoveries and hypotheses on previously uncharacterized phosphorylation
events, we further integrated information on availability of corresponding
antibodies from Cell Signaling Technology for proteins and sites that are
homologous between Drosophila and human to help users with experimental
- Protein Abundance
Protein expression levels from a comprehensive study covering the complete
Drosophila melanogaster life cycle are plotted. On this
tab, a user can view the stages of the Drosophila life cycle during
which a protein of interest is expressed.
- Bodenmiller B, Campbell D, Gerrits B, Lam H, Jovanovic M, Picotti P, Schlapbach R,
Aebersold R. 2008. PhosphoPep--a database of protein phosphorylation sites in model
organisms. Nat Biotechnol 26:1339-1340.
- Hilger M, Bonaldi T, Gnad F, Mann M. 2009. Systems-wide analysis of a phosphatase
knock-down by quantitative proteomics and phosphoproteomics. Mol Cell Proteomics
- Zhai B, Villen J, Beausoleil SA, Mintseris J, Gygi SP. 2008. Phosphoproteome
analysis of Drosophila melanogaster embryos. J Proteome Res 7:1675-1682.
- Hu Y, Flockhart I, Vinayagam A, Bergwitz C, Berger B, Perrimon N, Mohr SE. 2011.
An integrative approach to ortholog prediction for disease-focused and other
functional studies. BMC Bioinformatics 12:357.
- Casas-Vila N, Bluhm A, Sayols S, Dinges N, Dejung M, Altenhein T, Kappei D,
Altenhein B, Roignant JY, Butter F. 2017. The developmental proteome of Drosophila
melanogaster. Genome Res 27:1273-1285.