Intrinsic Disorder and Protein-Protein Interactions in Intra-Nuclear Compartments
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Int. J. Mol. Sci. 2016, 17, 24 S1/S22 Supplementary Materials: Compartmentalization and Functionality of Nuclear Disorder: Intrinsic Disorder and Protein-Protein Interactions in Intra-Nuclear Compartments Fanchi Meng, Insung Na, Lukasz Kurgan and Vladimir N. Uversky 0.8 0.7 0.6 0.5 0.4 0.3 0.2 Disorder content 0.1 0.0 Nuclear Speckle bodies Nucleolus Chromatin Cajal Body Nuclear Pore PML nuclear Perinucleolar NNUCLEAR or PPInnuclear Nuclear Lamina Nuclear Figure S1. Disorder content for the nuclear proteins with annotated intra-nuclear compartments (red boxplots; NUCLEARa dataset), with annotated and predicted intra-nuclear compartments (black boxplots; NUCLEARap dataset), and with annotated and predicted intra-nuclear compartments in the PPI network (blue boxplots; PPINUCLEARap dataset). The leftmost set of three boxplots shows all non-nuclear proteins (red and black boxplots; NNUCLEAR dataset) and the non-nuclear proteins in the PPI network (blue boxplots; PPINNUCLEAR dataset). The box plots include the first quartile, median andthird quartile while whiskers correspond to the 10th and 90th centiles of the disorder content of proteins in a given protein set. Disorder was annotated with the consensus of Espritz and IUPred. Int. J. Mol. Sci. 2016, 17, 24 S2/S22 Table S1. Disorder content, fraction of disordered proteins, and abundance of disordered domains for the nuclear proteins in specific intra-nuclear compartments from the NUCLEARa and NUCLEARap datasets and for the non-nuclear proteins from the NNUCLEAR dataset. Disorder was annotated with the consensus of Espritz and IUPred. Disorder Content Fraction of Fraction of Proteins with Disordered Domains Normalized Number Disordered of Disordered Localization Dataset Median Mean Proteins %DisDomProt %3+DisDomProt %5+DisDomProt Domains %DisProt %DisDom1K Value p-Value Value p-Value Value p-Value Value p-Value Value p-Value Value p-Value Value p-Value Non-nuclear NNUCLEAR 0.12 - 0.20 - 0.17 - 0.42 - 0.11 - 0.04 - 1.72 - NUCLEARa 0.11 0.002 0.17 0.007 0.14 0.002 0.57 0.182 0.16 0.082 0.08 0.002 1.49 0.002 Nuclear Pore NUCLEARap 0.11 0.002 0.17 0.648 0.13 0.002 0.59 0.764 0.21 0.002 0.10 0.322 1.51 0.867 NUCLEARa 0.15 0.550 0.21 0.984 0.17 0.619 0.65 0.019 0.19 0.703 0.10 0.168 2.14 0.417 Nuclear Lamina NUCLEARap 0.15 0.069 0.22 0.111 0.19 0.207 0.66 0.009 0.23 0.030 0.13 0.002 2.25 0.009 NUCLEARa 0.22 0.000 0.29 0.000 0.26 0.000 0.65 0.000 0.16 0.000 0.04 0.751 2.37 0.002 Nucleolus NUCLEARap 0.25 0.000 0.29 0.000 0.27 0.000 0.65 0.000 0.14 0.000 0.03 0.321 2.58 0.000 NUCLEARa 0.26 0.000 0.30 0.001 0.35 0.001 0.53 0.035 0.20 0.002 0.06 0.002 2.32 0.015 Cajal Body NUCLEARap 0.26 0.002 0.30 0.000 0.29 0.002 0.53 0.000 0.17 0.000 0.06 0.002 2.52 0.000 NUCLEARa 0.27 0.000 0.29 0.000 0.30 0.002 0.76 0.000 0.31 0.000 0.09 0.210 2.68 0.000 PML-NBs NUCLEARap 0.29 0.002 0.31 0.000 0.30 0.000 0.80 0.000 0.34 0.000 0.12 0.002 2.86 0.000 NUCLEARa 0.31 0.000 0.34 0.000 0.31 0.000 0.80 0.000 0.33 0.000 0.14 0.000 2.98 0.002 Chromatin NUCLEARap 0.32 0.000 0.33 0.000 0.34 0.002 0.79 0.000 0.33 0.000 0.14 0.000 3.17 0.000 NUCLEARa 0.27 0.002 0.35 0.000 0.38 0.000 0.79 0.002 0.42 0.002 0.04 0.002 3.21 0.000 Perinucleolar NUCLEARap 0.34 0.001 0.36 0.000 0.40 0.002 0.80 0.002 0.44 0.002 0.08 0.002 3.12 0.000 NUCLEARa 0.33 0.000 0.38 0.000 0.44 0.000 0.77 0.000 0.23 0.000 0.07 0.002 2.88 0.000 Nuclear Speckle NUCLEARap 0.36 0.002 0.38 0.000 0.45 0.000 0.77 0.000 0.22 0.000 0.06 0.003 3.07 0.000 Int. J. Mol. Sci. 2016, 17, 24 S3/S22 Table S2. Fraction of hub and intra-compartment hub proteins, average number of all and intra-compartment protein-protein interactions (PPIs), disorder content, fraction of disordered proteins, and abundance of disordered domains for the nuclear proteins in specific intra-nuclear compartments from the PPINUCLEARap datasets and for the non-nuclear proteins from the PPINNUCLEAR dataset. Disorder was annotated with the consensus of Espritz and IUPred. PPIs When Excluding Interactions Disorder All PPIs Fraction of Proteins with Disordered Domains across Compartments Content Normalized Fraction of Average number Number of Fraction Disordered Localization Average of Disordered Fraction of Intra- Proteins Number of Intra- Median Mean %DisDomProt %3+DisDomProt %5+DisDomProt Domains of Hubs Compartment %DisProt PPIs Compartment %DisDom1K Hubs PPIs Non-nuclear 0.17 5.28 0.17 5.28 0.11 0.18 0.14 0.46 0.12 0.04 1.62 Nuclear Pore 0.31 8.31 0.22 5.59 0.08 0.15 0.10 0.51 0.16 0.08 1.39 Nuclear Lamina 0.27 7.27 0.20 4.76 0.15 0.22 0.19 0.63 0.23 0.13 2.31 Nucleolus 0.32 11.69 0.27 9.36 0.23 0.28 0.26 0.66 0.14 0.03 2.51 Cajal Body 0.30 9.16 0.22 6.22 0.23 0.27 0.24 0.46 0.16 0.06 2.46 PML-NBs 0.51 11.76 0.35 7.69 0.30 0.31 0.33 0.81 0.36 0.12 2.95 Chromatin 0.38 9.45 0.29 6.33 0.34 0.36 0.37 0.86 0.39 0.17 3.27 Perinucleolar 0.58 14.42 0.38 7.88 0.34 0.37 0.42 0.79 0.46 0.08 3.09 Nuclear Speckle 0.30 7.72 0.23 5.60 0.35 0.38 0.45 0.77 0.24 0.07 3.11 Int. J. Mol. Sci. 2016, 17, 24 S4/S22 0.8 + + + + 0.7 + + 0.6 0.5 − = 0.4 + + + 0.3 + + Disorder content Disorder + = 0.2 − 0.1 0.0 Nucleolus PML-NBs Chromatin Cajal BodyCajal Nuclear Pore Perinucleolar NNUCLEAR Nuclear Lamina Nuclear Nuclear Speckle Figure S2. Disorder content of the non-nuclear proteins from the NNUCLEAR dataset and proteins in the considered intra-nuclear compartment from the NUCLEARa dataset. The box plots include the first quartile, median and third quartile while whiskers correspond to the 10th and 90th centiles of the disorder content of proteins in a given protein set. The black circle marker is the mean value of the disorder content. The significance of the differences in the median (mean) disorder content between proteins in a given compartment and non-nuclear proteins is annotated above the whiskers (right ofthe marker); + and − mean that the content of the nuclear proteins is significantly higher and lower (p-value < 0.01), respectively; “=” means that the difference is not significant (p-value ≥ 0.01). Disorder was annotated with the consensus of Espritz and IUPred. 45% %DisProt 3.2 %DisDom1K 3.0 40% 2.9 2.7 35% 2.4 2.3 30% 2.1 25% 1.7 20% 1.5 15% 17% 14% 17% 26% 30% 31% 35% 38% 44% %DisProt (fraction of disordered proteins) disordered of (fraction %DisProt 10% Nucleolus PML-NBs Chromatin Cajal Body Cajal Nuclear Pore Nuclear Perinucleolar NNUCLEAR uclear Lamina uclear uclear Speckleuclear N N Figure S3. Fraction of disordered proteins (black bars) and normalized number of disordered domains (gray line) for the non-nuclear proteins from the NNUCLEAR dataset and proteins in the considered intra-nuclear compartment from the NUCLEARa dataset. Disorder was annotated with the consensus of Espritz and IUPred. Int. J. Mol. Sci. 2016, 17, 24 S5/S22 70% Fraction of proteins with no disordered domains %3+DisDomProt (fraction of proteins with at least 3 disordered domains) 60% 50% 40% 30% Fraction of proteins of Fraction 20% 10% 58%11% 35% 16% 47% 20% 43% 16% 23% 23% 35% 19% 20% 33% 24% 31% 0% Nucleolus PML-NBs Chromatin Cajal Body Cajal Nuclear PoreNuclear NNUCLEAR uclear Speckle Nuclear Lamina Nuclear N Figure S4. Fraction of proteins with no disordered domains (gray bars) and with at least 3 disordered domains (%3+DisDomProt) (black bars) for the non-nuclear proteins from the NNUCLEAR dataset and proteins in the considered intra-nuclear compartment from the NUCLEARa dataset. Disorder was annotated with the consensus of Espritz and IUPred. Int. J. Mol. Sci. 2016, 17, 24 S6/S22 Table S3. Disorder content, fraction of disordered proteins, and abundance of disordered domains for the nuclear proteins from the NUCLEARap dataset grouped by the number of intra-nuclear compartments they are localized in. Disorder was annotated with the consensus of Espritz and IUPred.