LiteFold/DisProt huggingface dataset:
Protein: DP04255 (UniProt O60016)
Region: residues 69	to 191
Annotation: disorder (Structural state)
Evidence: heteronuclear single quantum coherence spectroscopy evidence used in manual assertion
Supporting statements:
The chromodomain and the SET domain are connected by a highly disordered region comprising residues S69-S191.
Cross-references: BMRB:27903
Protein: DP04255 (UniProt O60016)
Region: residues 69	to 191
Annotation: flexible linker (Disorder function)
Evidence: heteronuclear single quantum coherence spectroscopy evidence used in manual assertion
Supporting statements:
The chromodomain and the SET domain are connected by a highly disordered region comprising residues S69-S191.
Cross-references: BMRB:27903
Protein: DP04255 (UniProt O60016)
Region: residues 69	to 191
Annotation: nucleosome binding (Molecular function)
Evidence: co-immunoprecipitation evidence used in manual assertion
Supporting statements:
Our data show that the Clr4 ΔCD construct (residues 69–490) binds unmodified and tailless nucleosomes, while the Pre-SET-Post construct (residues 258–490) shows no binding to any kind of nucleosomes.
To further dissect the role of the disordered region in binding to the nucleosome, we generated Clr4 constructs comprising residues 1–191 (Clr4_1–191 which includes CD and the disordered region) and 192–490 (Clr4_192–460 which includes the SET domain). The pull-down assays revealed that the Clr4_1–191 construct, but not Clr4_192–490, binds H3KC9me3 and tailless nucleosomes (Figure 1C). These data show that Clr4 can bind the nucleosome independent of H3K9 methylation through the highly disordered region comprising residues 70–191.
Protein: DP04255 (UniProt O60016)
Region: residues 113	to 170
Annotation: nucleosome binding (Molecular function)
Evidence: heteronuclear single quantum coherence spectroscopy evidence used in manual assertion
Supporting statements:
The interaction of the C-terminal α-helix of the chromodomain with the H3KC9me3 nucleosome is more extensive when the disordered region is present (Figure 2B and Supplementary Figure S2D), suggesting that the disordered region stabilizes the CD interaction with the core of the nucleosome (Supplementary Figure S4A and B).
Altogether, our data show that the disordered region tethers Clr4 CD to the nucleosome, and that CD interacts with the unmodified nucleosome in a similar way as with the H3KC9me3 nucleosome.
Moreover, we observe several interactions of the disordered region with the H3KC9me3 nucleosome. This includes the patches 113KKVFS117, 123RQSR126, 147TNSK150 and 164QKRELVS170 in the disordered region.
Cross-references: BMRB:27905
Protein: DP04255 (UniProt O60016)
Region: residues 164	to 174
Annotation: disorder to order (Structural transition)
Evidence: heteronuclear single quantum coherence spectroscopy evidence used in manual assertion
Supporting statements:
Notably, the propensity for secondary structure elements was visible at the intrinsically disordered region upon Clr4_1–191 binding to the H3KC9me3 nucleosome. The patch 113KKVFS117 incorporates the β-strand and 164QKRELVS174 shows features of an α-helix (Figure 2D).
Our data show that Clr4 binds the nucleosome with its disordered region independent of H3K9 methylation and this induces formation of an α-helix and β-sheet in this region.
Notably, we found the propensity for secondary structure elements in the intrinsically disordered region between S69 and S192 with β-sheet β4 (113KKVFS117) and α-helix α3 (164QKRELVS174). These data show that the nucleosome induces formation of secondary structure elements in the disordered region of Clr4 and these elements bind the core of the nucleosome (40–42).
Cross-references: BMRB:27905
BMRB:27903
Protein: DP04255 (UniProt O60016)
Region: residues 164	to 170
Annotation: histone methyltransferase activity (H3-K9 specific) (Molecular function)
Evidence: loss-of-function mutant phenotype evidence used in manual assertion
Supporting statements:
 We mutated two patches in the Clr4 disordered region that make contacts with the nucleosome in our NMR data. The patch 164QKRELVS170 in the clr4 gene was mutated to 164SGSGSGS170 and the patch 147TNSK150 to 147SGSG150, respectively, generating the MUT12 construct. We purified wild-type and mutant Clr4 and determined their methlytransferase activity by western blot (Supplementary Figure S7A). Our biochemical data show that mutations in these two patches reduced Clr4 interaction with the nucleosome and the methyltransferase activity (Figure 3A–C). This indicates that interaction of the disordered region with the nucleosome stabilizes Clr4 on the nucleosome and promotes H3K9 methylation.
This indicates that the interaction of Clr4 disordered region with the nucleosome increases efficiency and the kinetics of H3K9 methylation and heterochromatin establishment.
Taken together, our data show that in absence of H3K9 methylation, Clr4 disordered region binds the nucleosome which stabilizes the complex to deposit the initial H3K9 methylation. This interaction increases the efficiency of H3K9 methylation and heterochromatin establishment.
Protein: DP04255 (UniProt O60016)
Region: residues 147	to 151
Annotation: histone methyltransferase activity (H3-K9 specific) (Molecular function)
Evidence: loss-of-function mutant phenotype evidence used in manual assertion
Supporting statements:
 We mutated two patches in the Clr4 disordered region that make contacts with the nucleosome in our NMR data. The patch 164QKRELVS170 in the clr4 gene was mutated to 164SGSGSGS170 and the patch 147TNSK150 to 147SGSG150, respectively, generating the MUT12 construct. We purified wild-type and mutant Clr4 and determined their methlytransferase activity by western blot (Supplementary Figure S7A). Our biochemical data show that mutations in these two patches reduced Clr4 interaction with the nucleosome and the methyltransferase activity (Figure 3A–C). This indicates that interaction of the disordered region with the nucleosome stabilizes Clr4 on the nucleosome and promotes H3K9 methylation.
This indicates that the interaction of Clr4 disordered region with the nucleosome increases efficiency and the kinetics of H3K9 methylation and heterochromatin establishment.
Taken together, our data show that in absence of H3K9 methylation, Clr4 disordered region binds the nucleosome which stabilizes the complex to deposit the initial H3K9 methylation. This interaction increases the efficiency of H3K9 methylation and heterochromatin establishment.
Protein: DP04256 (UniProt P54820)
Region: residues 48	to 69
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
In the crystal structure this region is composed of an irregular segment containing residues 1–33 and a small α-helix (residues 34–41). The linker segment 13–32
is essentially disordered in the electron density.
The region the authors report as 13-32, refers to the 48-69 region of the UniProt sequence.
Cross-references: PDB:3M97
Protein: DP04256 (UniProt P54820)
Region: residues 38	to 47
Annotation: disorder (Structural state)
Evidence: combinatorial experimental and author inference evidence contained in single publication used in manual assertion
Supporting statements:
In the crystal structure this region is composed of an irregular segment containing residues 1–33 and a small α-helix (residues 34–41). The linker segment 13–32
is essentially disordered in the electron density. In contrast, residues 1–12 are clearly
visible in the electron-density map as they are artificially rigidified by a crystal contact to a neighbouring subunit mediated by Zn2+ ions (see x3.3). Therefore, we assume that in the cell the irregular segment is highly flexible as previously predicted by Berry & Trumpower (1985)
The region the authors report as 1-12, refers to the 38-47 region of the UniProt sequence. 
Cross-references: PDB:3M97
Protein: DP04256 (UniProt P54820)
Region: residues 38	to 69
Annotation: flexible linker (Disorder function)
Evidence: combinatorial experimental and author inference evidence contained in single publication used in manual assertion
Supporting statements:
Residues 1–40 of fragment B link the globular cytochrome c domain and the N-terminal membrane anchor (the latter was absent in the construct used for crystallization).
In the crystal structure this region is composed of an irregular segment containing residues 1–33 and a small α-helix (residues 34–41). The linker segment 13–32
is essentially disordered in the electron density. In contrast, residues 1–12 are clearly visible in the electron-density map as they are artificially rigidified by a crystal contact to a neighbouring subunit mediated by Zn2+ ions (see x3.3). Therefore, we assume that in the cell the irregular segment is highly flexible as previously predicted by Berry & Trumpower (1985).
The region the authors report as 1-40, refers to the 38-69 region of the UniProt sequence.
Cross-references: PDB:3M97
Protein: DP04257 (UniProt Q9NZI8)
Region: residues 157	to 194
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
1H-15N Heteronuclear Single Quantum Coherence (HSQC) experiments revealed a small dispersion of backbone amide signals, thus validating the disordered nature of the linker segments (Supplementary Fig. 8A-D). 
Cross-references: BMRB:52567
Protein: DP04257 (UniProt Q9NZI8)
Region: residues 344	to 404
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
1H-15N Heteronuclear Single Quantum Coherence (HSQC) experiments revealed a small dispersion of backbone amide signals, thus validating the disordered nature of the linker segments (Supplementary Fig. 8A-D). 
Cross-references: BMRB:52568
Protein: DP04257 (UniProt Q9NZI8)
Region: residues 179	to 183
Annotation: regulation of stress granule assembly (Biological process)
Evidence: loss-of-function mutant phenotype evidence used in manual assertion
Supporting statements:
Here, we map stress-regulated phosphorylation sites in IGF2BP1 by targeted mass spectrometry analyzes to uncover mechanisms that control IGF2BP1 outputs. Using in vitro reconstitution, biochemistry, and structural methods, we dissect how IGF2BP1 phosphorylation in its disordered linker regions regulates function. We show that phosphorylation of the disordered linkers regulates the propensity of IGF2BP1 to form RNP granules in vitro and in cells by modulating low affinity interaction networks.
Quantification of the IGF2BP1-RNA condensates (Supplementary Fig. 3A, see materials and methods) revealed that the average size of condensates and the total area of condensates formed by the S181E mutant were smaller compared to the wild-type IGF2BP1, indicating that the IGF2BP1 S181E mutant is impaired in condensate formation (Fig. 2H, J, Supplementary Fig. 4F-I, Supplementary Table 3, median area per condensate: wild-type: 7.0 µm, S181E: 5.7 µm, mean total area: wild-type: 7753 µm², S181E: 4691 µm², at 5 µM protein and RNA concentration).
IGF2BP1 is phosphorylated at Ser181 in response to proteotoxic stress. When this residue is replaced with a phosphomimetic mutant (Glu), the ability of IGF2BP1 to form condensates is impaired, indicating that stress-induced phosphorylation at this site regulates granule formation.
Protein: DP04257 (UniProt Q9NZI8)
Region: residues 394	to 398
Annotation: regulation of stress granule assembly (Biological process)
Evidence: loss-of-function mutant phenotype evidence used in manual assertion
Supporting statements:
Here, we map stress-regulated phosphorylation sites in IGF2BP1 by targeted mass spectrometry analyzes to uncover mechanisms that control IGF2BP1 outputs. Using in vitro reconstitution, biochemistry, and structural methods, we dissect how IGF2BP1 phosphorylation in its disordered linker regions regulates function. We show that phosphorylation of the disordered linkers regulates the propensity of IGF2BP1 to form RNP granules in vitro and in cells by modulating low affinity interaction networks.
Intriguingly, in contrast to the S181E mutant, the Y396E mutant formed larger condensates with a larger total area under the same experimental conditions (Fig. 2I, J, Supplementary Fig. 4 F, H, I, Supplementary Table 3, median area per droplet: Y396E 10.8 µm, mean total area: Y396E 9298 µm², at 5 µM protein and RNA concentration).
IGF2BP1 is phosphorylated at Tyr396 in response to proteotoxic stress. When this residue is replaced with a phosphomimetic mutant (Glu), the ability of IGF2BP1 to form condensates is affected, indicating that stress-induced phosphorylation at this site regulates granule formation
Protein: DP04257 (UniProt Q9NZI8)
Region: residues 170	to 175
Annotation: RNA binding (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Linker 1 contains an RGG-RG motif which is in the vicinity of S181 that shows evolutionary conservation in mammals and some vertebrate species (Supplementary Fig. 1A). Therefore, we investigated whether linker 1 could contribute to protein-RNA interactions by measuring HSQC spectra of linker 1 in the presence of a model RNA (12xUG) that is recognized by RGG containing proteins through formation of an RNA quadruplex69 and a 10 nt RNA derived from XBP1. Titration of the wild-type linker 1 with the 12xUG RNA resulted in large chemical shift perturbations and a decrease in signal intensity of the residues around the RGG-RG motif (G170, G172 and G175, Fig. 5B-D and Supplementary Fig. 10J, K).
Protein: DP04257 (UniProt Q9NZI8)
Region: residues 179	to 183
Annotation: negative regulation of RNA binding (Biological process)
Evidence: loss-of-function mutant phenotype evidence used in manual assertion
Supporting statements:
Linker 1 contains an RGG-RG motif which is in the vicinity of S181 that shows evolutionary conservation in mammals and some vertebrate species (Supplementary Fig. 1A). Therefore, we investigated whether linker 1 could contribute to protein-RNA interactions by measuring HSQC spectra of linker 1 in the presence of a model RNA (12xUG) that is recognized by RGG containing proteins through formation of an RNA quadruplex69 and a 10 nt RNA derived from XBP1. Titration of the wild-type linker 1 with the 12xUG RNA resulted in large chemical shift perturbations and a decrease in signal intensity of the residues around the RGG-RG motif (G170, G172 and G175, Fig. 5B-D and Supplementary Fig. 10J, K).
Notably, the linker 1 phosphomimetic mutant S181E was impaired in binding to RNA, evident in lower CSPs and a lower drop in the signal intensity around the phosphorylation site upon its titration with the 12xUG RNA.
The NMR data revealed that while linker 1 binds to RNA, linker 2 forms low-affinity interactions with the folded domains in IGF2BP1, and both interactions are modulated in the relevant phosphomimetic mutants.
This evidence indicates the phosphorylated version of this region regulates negatively the RNA association.
Protein: DP04257 (UniProt Q9NZI8)
Region: residues 388	to 395
Annotation: self-assembly (Disorder function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The NMR analyzes revealed that titration of wild-type linker 2 with RRM1-2 as well as the KH1-2 domains showed small CSPs around aa S388-P395 (aa 388-SSVTGAP-395) (CSP > 0.015) (Supplementary Fig. 11A-F) indicating that linker 2 interacts with these domains with a low affinity in the millimolar range.
Titration of linker 2 with KH3-4 domains displayed the largest CSPs observed for all folded domains, revealing that linker 2 most strongly interacts with KH3-4 dimers (Fig. 5E-G, Supplementary Fig. 11G-H).
The NMR data revealed that while linker 1 binds to RNA, linker 2 forms low-affinity interactions with the folded domains in IGF2BP1, and both interactions are modulated in the relevant phosphomimetic mutants.
Protein: DP04257 (UniProt Q9NZI8)
Region: residues 179	to 183
Annotation: phosphorylation display site (Disorder function)
Evidence: mass spectrometry evidence used in manual assertion
Supporting statements:
The identified phosphopeptides mapped to the RRM1 domain (aa S73), disordered linker 1 (aa S181), KH1 (aa T249), KH2 and KH3 domains (aa S436, S438, T446) (Fig. 1C, Supplementary Fig. 1B).
Protein: DP04257 (UniProt Q9NZI8)
Region: residues 394	to 398
Annotation: phosphorylation display site (Disorder function)
Evidence: mass spectrometry evidence used in manual assertion
Supporting statements:
In line with the published results7, we detected phosphorylation of the recombinant IGF2BP1 at Y396 by the Src kinase in vitro.
Protein: DP04257 (UniProt Q9NZI8)
Region: residues 157	to 194
Annotation: flexible linker (Disorder function)
Evidence: heteronuclear single quantum coherence spectroscopy evidence used in manual assertion
Supporting statements:
1H-15N Heteronuclear Single Quantum Coherence (HSQC) experiments revealed a small dispersion of backbone amide signals, thus validating the disordered nature of the linker segments (Supplementary Fig. 8A-D).
Cross-references: BMRB:52567
Protein: DP04257 (UniProt Q9NZI8)
Region: residues 344	to 404
Annotation: flexible linker (Disorder function)
Evidence: heteronuclear single quantum coherence spectroscopy evidence used in manual assertion
Supporting statements:
1H-15N Heteronuclear Single Quantum Coherence (HSQC) experiments revealed a small dispersion of backbone amide signals, thus validating the disordered nature of the linker segments (Supplementary Fig. 8A-D).
Cross-references: BMRB:52568
Protein: DP04258 (UniProt Q15022)
Region: residues 168	to 181
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The L1, L3, L5, and L7 loops on the distal side away from Rbbp4 are all disordered, implicating that they may be involved in other functions (Fig. 3D).
Cross-references: PDB:5WAI
Protein: DP04258 (UniProt Q15022)
Region: residues 256	to 293
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The L1, L3, L5, and L7 loops on the distal side away from Rbbp4 are all disordered, implicating that they may be involved in other functions (Fig. 3D).
Cross-references: PDB:5WAI
Protein: DP04258 (UniProt Q15022)
Region: residues 323	to 350
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The L1, L3, L5, and L7 loops on the distal side away from Rbbp4 are all disordered, implicating that they may be involved in other functions (Fig. 3D).
Cross-references: PDB:5WAI
Protein: DP04258 (UniProt Q15022)
Region: residues 364	to 422
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The L1, L3, L5, and L7 loops on the distal side away from Rbbp4 are all disordered, implicating that they may be involved in other functions (Fig. 3D).
Cross-references: PDB:5WAI
Protein: DP04258 (UniProt Q15022)
Region: residues 497	to 513
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The L1, L3, L5, and L7 loops on the distal side away from Rbbp4 are all disordered, implicating that they may be involved in other functions (Fig. 3D).
Cross-references: PDB:5WAI
Protein: DP04258 (UniProt Q15022)
Region: residues 150	to 188
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Missing electron density for the region.
Cross-references: PDB:5WAK
Protein: DP04258 (UniProt Q15022)
Region: residues 201	to 241
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Missing electron density for the region.
Cross-references: PDB:5WAK
Protein: DP04258 (UniProt Q15022)
Region: residues 251	to 367
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Missing electron density for the region.
Cross-references: PDB:5WAK
Protein: DP04258 (UniProt Q15022)
Region: residues 380	to 423
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Missing electron density for the region.
Cross-references: PDB:5WAK
Protein: DP04258 (UniProt Q15022)
Region: residues 497	to 510
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Missing electron density for the region.
Cross-references: PDB:5WAK
Protein: DP04258 (UniProt Q15022)
Region: residues 201	to 241
Annotation: order (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Comparing the two structures, an additional domain of Suz12 becomes better ordered in S12R4J2A2 due to Aebp2 binding (Fig. 1 and S1A).
Cross-references: PDB:5WAI
Protein: DP04258 (UniProt Q15022)
Region: residues 201	to 241
Annotation: disorder to order (Structural transition)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Comparing the two structures, an additional domain of Suz12 becomes better ordered in S12R4J2A2 due to Aebp2 binding (Fig. 1 and S1A).
Cross-references: PDB:5WAI
PDB:5WAK
Protein: DP04259 (UniProt Q9H9Q4)
Region: residues 229	to 299
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
1H chemical shift dispersion, secondary structural propensity, 15N–{1H} heteronuclear nuclear Overhauser effect (hNOE) and small-angle X-ray scattering (SAXS) experiments jointly indicated the lack of stable secondary structure elements in the XLFCTR either alone or in the context of the full-length protein construct (Supplementary Fig. 3a,b and Extended Data Fig. 2), defining it as an intrinsically disordered region (IDR).
Cross-references: BMRB:52387
Protein: DP04259 (UniProt Q9H9Q4)
Region: residues 295	to 299
Annotation: protein binding (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
 We titrated 15N XLFCTR with the Ku80 von Willebrand domain (Ku80vWA) and observed that XLF–Ku interactions mainly involved the residue K293 and the last five residues (295RGLFS299), with notable chemical shift perturbations (CSPs) and peaks in the slow exchange regime, while residues 283–292 were only slightly perturbed upon binding to Ku80vWA (Fig. 2c,d).
Altogether, we show that the disordered CTR of XLF is an interaction hub, which binds weakly to Ku, DNA, LIG4 and the folded domain of XLF in an intramolecular or intermolecular fashion.
Protein: DP04259 (UniProt Q9H9Q4)
Region: residues 282	to 294
Annotation: DNA binding (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Therefore, the positively charged region (residues 282–294) is the core of the DNA-binding motif (DBM) (Fig. 2i).