About D2P2

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What is D2P2

D2P2 is a database of disordered protein predictions. A battery of disorder predictors and their variants: VL-XT, VSL2b, PrDOS, PV2, Espritz and IUPred, are run on all protein sequences from 1,765 complete proteomes (to be updated as more genomes are completed). Integrated with these results are all of the predicted (mostly structured) SCOP domains using the SUPERFAMILY predictor. These disorder/structure annotations together enable comparison of the disorder predictors with each other and examination of the overlap between disordered predictions and SCOP domains on a large scale. D2P2 will increase our understanding of the interplay between disorder and structure, the genomic distribution of disorder, and its evolutionary history. The parsed data are made available in a unified format for download as flat files or SQL tables either by genome (via the browse heading), by predictor (via the download heading), or for the complete set (via download heading). This interactive website provides a graphical view (see 'assignments we provide' below) of each protein annotated with the SCOP domains and disordered regions from all predictors overlaid (or shown as a consensus). There are statistics and tools for browsing and comparing genomes and their disorder within the context of their position on the tree of life and disorder content.

What is a disordered protein?

  • PDB:2fft
    All states of TSP9 PDB:2fft

    A single stable helix (black) seperates two disordered segments (blue & green-red) of the Thylakoid soluble phosphoprotein TSP9. All known states from NMR are shown super imposed.

Intrinsically unstructured (IUP) or disordered proteins, are proteins that exist in a naturally unfolded state and lack stable tertiary structure in vivo. IUPs exist as highly flexible polypeptide chains behaving as an ensemble of conformational states with no stable tertiary structure (1). Regions of IDP can exist as unfolded chains or molten globules with well-developed secondary structure and often function through transition between differently folded states (2). Mechanisms for functional conformational transition include binding with other proteins, nucleic acids, various small molecules, and numerous posttranslational modifications, such as phosphorylation, which has been shown to be especially important (3,4). Biological functions of known IDPs are varied and their roles include: instigation of protein complex formation, molecular recognition as seen in nucleoporins of the nuclear pore complex (5), signal transduction, transcriptional regulation and many other functions (6,7) too numerous to list here.

Disordered regions are highly enriched for many forms of post translational modifications. A good example is the Thylakoid soluble phosphoprotein (TSP9) from Spinach (shown left), which was shown to flip between a folded trans-thylakoid-membrane state and an unfolded but stromal accessible state with the addition of phosphorous groups in two key disordered regions (4).

  1. Uversky,V.N., Gillespie,J.R., Fink,A.L. (2000) Why are “natively unfolded” proteins unstructured under physiologic conditions? Proteins., 41(3), 415-427.
  2. Uversky,V.N. (2002) Natively unfolded proteins: A point where biology waits for physics. Protein Sci.,11(4), 739-756.
  3. Iakoucheva,L.M., Radivojac,P., Brown,C.J., O'Connor,T.R., Sikes,J.G., Obradovic,Z., and Dunker,A.K. (2004) The importance of intrinsic disorder for protein phosphorylation. Nucleic Acids Res. 32(3), 1037-1049.
  4. Song,J., Lee,M.S., Carlberg,I., Vener,A.V., and Markley,J.L. (2006) Micelle-induced Folding of Spinach Thylakoid Soluble Phosphoprotein of 9 kDa and its Functional Implications. Biochemistry., 45(51):,15633-15643.
  5. Yamada J., Phillips J.L., Patel S., Goldfien G., Calestagne-Morelli A., Huang H., Reza R., Acheson J., Krishnan V.V., Newsam S., Gopinathan A., Lau E.Y., Colvin M.E., Uversky V.N., Rexach M.F. (2010) A bimodal distribution of two distinct categories of intrinsically-disordered structures with separate functions in FG nucleoporins. Molecular and Cellular Proteomics. 9(10), 2205-2224. PMID: 20214631.
  6. Dunker,A.K., Silman,I., Uversky,V.N., Sussman,J.L. (2008) Function and structure of inherently disordered proteins. Curr. Opin. Struct. Biol., 18, 756-764.
  7. Dyson,H.J. and Wright,P.E. (2005) Intrinsically unstructured proteins and their functions. Nature Reviews Mol. Cell Bio. 6, 197-208

Assignments we provide

The figure to the right shows two transcripts of the Human gene BIN1. With the longer transcript ENSP00000316779 we can see that the BAR/IMD domain has undergone an insertion of disorderied sequence, fragmenting the structured region predicted by SUPERFAMILY. Looking at the consensus bar we can also see that the insert has high agreement between the disorder predictors, and that it's not conflicting with the SUPERFAMILY interpretation (green rather than red).

Assignments linked from other resources