LiteFold/DisProt huggingface dataset:
Protein: DP01129 (UniProt P12296)
Region: residues 37	to 67
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance evidence used in manual assertion
Supporting statements:
Surprisingly, when one or two phosphates were added, the overall proteins still configured largely as random coil (Fig. 1 and Fig. S6 B–D).
The remainder of each protein is random coil.
The figure 1 shows the secondary when the protein is without PTMs, phosphorilated or binding protein Ran. The secondary structure along the sequence is shown and the rest of the protein is random coil.
Cross-references: PDB:2MMH
PDB:2MMI
PDB:2MML
PDB:2MMK
Protein: DP01129 (UniProt P12296)
Region: residues 1	to 15
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance evidence used in manual assertion
Supporting statements:
Surprisingly, when one or two phosphates were added, the overall proteins still configured largely as random coil (Fig. 1 and Fig. S6 B–D).
The remainder of each protein is random coil.
The figure 1 shows the secondary when the protein is without PTMs, phosphorilated or binding protein Ran. The secondary structure along the sequence is shown and the rest of the protein is random coil.
Cross-references: PDB:2MMH
PDB:2MMI
PDB:2MML
PDB:2MMK
Protein: DP01129 (UniProt P12296)
Region: residues 22	to 43
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance evidence used in manual assertion
Supporting statements:
Surprisingly, when one or two phosphates were added, the overall proteins still configured largely as random coil (Fig. 1 and Fig. S6 B–D).
The remainder of each protein is random coil.
The figure 1 shows the secondary when the protein is without PTMs, phosphorilated or binding protein Ran. The secondary structure along the sequence is shown and the rest of the protein is random coil.
Cross-references: PDB:2MMH
PDB:2MMI
PDB:2MML
PDB:2MMK
Protein: DP01129 (UniProt P12296)
Region: residues 46	to 67
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance evidence used in manual assertion
Supporting statements:
Surprisingly, when one or two phosphates were added, the overall proteins still configured largely as random coil (Fig. 1 and Fig. S6 B–D).
The remainder of each protein is random coil.
The figure 1 shows the secondary when the protein is without PTMs, phosphorilated or binding protein Ran. The secondary structure along the sequence is shown and the rest of the protein is random coil.
Cross-references: PDB:2MMH
PDB:2MMI
PDB:2MML
PDB:2MMK
Protein: DP01129 (UniProt P12296)
Region: residues 29	to 60
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance evidence used in manual assertion
Supporting statements:
When the 15N/13C protein labels were switched in Ran:LM0P complexes, the states of LM0P as influenced by Ran showed multiple peak shifts relative to free LM0P (Fig. 1 and Fig. S3A). The shifts included all residues in the hinge region, as had been anticipated from mutagenesis mapping (15). Also involved were regions from the carboxyl third of the protein. The zinc finger region did not change, maintaining the α1 and α2 helices. However, as with both phosphorylation datasets, the rest of (Ran):LM0P now became more compact (Fig. 4B).
Region disordered when it's bound to Ran
The figure 1 shows the secondary when the protein is without PTMs, phosphorilated or binding protein Ran. The secondary structure along the sequence is shown and the rest of the protein is random coil.
Cross-references: PDB:2MMH
PDB:2MMI
PDB:2MML
PDB:2MMK
Protein: DP01129 (UniProt P12296)
Region: residues 29	to 41
Annotation: protein binding (Molecular function)
Evidence: nuclear magnetic resonance evidence used in manual assertion
Supporting statements:
When the 15N/13C protein labels were switched in Ran:LM0P complexes, the states of LM0P as influenced by Ran showed multiple peak shifts relative to free LM0P (Fig. 1 and Fig. S3A). The shifts included all residues in the hinge region, as had been anticipated from mutagenesis mapping (15). Also involved were regions from the carboxyl third of the protein. The zinc finger region did not change, maintaining the α1 and α2 helices. However, as with both phosphorylation datasets, the rest of (Ran):LM0P now became more compact (Fig. 4B).
The LM0P hinge and acidic domains interact significantly with the proximal tip of the Ran COOH tail (aa 203–210), but the remainder of this segment is free to arch without steric hindrance, morphing and encircling central interaction residues of LM0P (Fig. 4D). 
Important Ran:LM0P contacts include T32:L37, A183:D41, P184:Y45, P185:E42, Q196:Y36, Y197:Y40; Y197:W44, A204:G34, A204:L38, and T207:N33 (Fig. 4E).
Cross-references: BMRB:19852
PDB:2MMH
PDB:2MMI
PDB:2MML
PDB:2MMK
BMRB:19854
Protein: DP01129 (UniProt P12296)
Region: residues 47	to 53
Annotation: protein binding (Molecular function)
Evidence: nuclear magnetic resonance evidence used in manual assertion
Supporting statements:
When the 15N/13C protein labels were switched in Ran:LM0P complexes, the states of LM0P as influenced by Ran showed multiple peak shifts relative to free LM0P (Fig. 1 and Fig. S3A). The shifts included all residues in the hinge region, as had been anticipated from mutagenesis mapping (15). Also involved were regions from the carboxyl third of the protein. The zinc finger region did not change, maintaining the α1 and α2 helices. However, as with both phosphorylation datasets, the rest of (Ran):LM0P now became more compact (Fig. 4B).
The LM0P hinge and acidic domains interact significantly with the proximal tip of the Ran COOH tail (aa 203–210), but the remainder of this segment is free to arch without steric hindrance, morphing and encircling central interaction residues of LM0P (Fig. 4D). 
Important Ran:LM0P contacts include T32:L37, A183:D41, P184:Y45, P185:E42, Q196:Y36, Y197:Y40; Y197:W44, A204:G34, A204:L38, and T207:N33 (Fig. 4E).
Cross-references: BMRB:19852
PDB:2MMH
PDB:2MMI
PDB:2MML
PDB:2MMK
BMRB:19854
Protein: DP01129 (UniProt P12296)
Region: residues 56	to 67
Annotation: protein binding (Molecular function)
Evidence: nuclear magnetic resonance evidence used in manual assertion
Supporting statements:
When the 15N/13C protein labels were switched in Ran:LM0P complexes, the states of LM0P as influenced by Ran showed multiple peak shifts relative to free LM0P (Fig. 1 and Fig. S3A). The shifts included all residues in the hinge region, as had been anticipated from mutagenesis mapping (15). Also involved were regions from the carboxyl third of the protein. The zinc finger region did not change, maintaining the α1 and α2 helices. However, as with both phosphorylation datasets, the rest of (Ran):LM0P now became more compact (Fig. 4B).
The LM0P hinge and acidic domains interact significantly with the proximal tip of the Ran COOH tail (aa 203–210), but the remainder of this segment is free to arch without steric hindrance, morphing and encircling central interaction residues of LM0P (Fig. 4D). 
Important Ran:LM0P contacts include T32:L37, A183:D41, P184:Y45, P185:E42, Q196:Y36, Y197:Y40; Y197:W44, A204:G34, A204:L38, and T207:N33 (Fig. 4E).
Cross-references: BMRB:19852
PDB:2MMH
PDB:2MMI
PDB:2MML
PDB:2MMK
BMRB:19854
Protein: DP01130 (UniProt P49757)
Region: residues 68	to 78
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
NMR data demonstrate that Ex3 in the free PTBi is intrinsically disordered
Protein: DP01130 (UniProt P49757)
Region: residues 68	to 78
Annotation: protein binding (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The Ex3-encoded sequence of Numb PTB is necessary for interaction with Mdm2
Protein: DP01131 (UniProt O14558)
Region: residues 1	to 56
Annotation: disorder (Structural state)
Evidence: cleavage assay evidence used in manual assertion
Supporting statements:
Since extensive crystallization efforts with the full-length human HSPB6 failed, we employed limited proteolysis to remove poorly ordered regions of this protein.
Protein: DP01131 (UniProt O14558)
Region: residues 24	to 39
Annotation: protein folding chaperone (Molecular function)
Evidence: loss-of-function mutant phenotype evidence used in manual assertion
Supporting statements:
The ΔN23 truncation showed approximately 60% of the chaperoning activity of the FL protein with 1:0.2 ratio insulin:sHSP, and was almost as efficient as the FL at higher ratios (Fig. 6A). In contrast, both ΔN56 and ΔN39 showed minimal chaperone activity for all concentrations tested.
In addition, we found that ΔN23 retained most of the chaperoning activity for reduced insulin when compared to the full-length HSPB6, but the ΔN39 truncation was a poor chaperone (Figs. 6A and S8). Altogether, the correlating self-association properties and the chaperoning capacity of truncated variants clearly suggest that the conserved region of HSPB6 plays an important functional role, although more structural data are required towards a complete mechanistic model.
Both ΔN39 and ΔN56 remove the conserved N-terminal region, and both lose chaperone activity completely. This indicates that the sequence between residues ~24–39 (and extending to ~56) is crucial for chaperone-like function.
Protein: DP01131 (UniProt O14558)
Region: residues 1	to 56
Annotation: disorder (Structural state)
Evidence: small-angle X-ray scattering evidence used in manual assertion
Supporting statements:
In addition the HSPB6 peaks are asymmetric, with the scattering tailing upwards at higher qRg values, suggesting that at all concentrations the protein is partially disordered. The combined evidence supports the hypothesis that in dilute solution the HSPB6 structure is based on the ACD dimer, having an oblate shape, flanked by N- and C- regions that are disordered.
The SAXS data confirm that the N-terminal domains of HSPB6 are poorly ordered, appearing as a ‘cloud’ of possible conformations in the final model (Fig. 5I).
Protein: DP01131 (UniProt O14558)
Region: residues 39	to 69
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The proximal half of the NTD (residues 39–69) is disordered in all chains, leaving an ambiguity in the interconnection of the N-terminal parts and the ACDs (see Figure 3B for details).
Cross-references: PDB:5LTW
Protein: DP01131 (UniProt O14558)
Region: residues 27	to 38
Annotation: order (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
In each of three complexes found in the crystallographic asymmetric unit, residues 1–20 of both NTDs, as well as residues 27–38 of one of the NTDs, could be traced. In addition, in one of the six NTDs, residues 21–26 were also traced, so that the structure of the entire region encompassing residues 1–38 could be established.
Cross-references: PDB:5LTW
Protein: DP01131 (UniProt O14558)
Region: residues 27	to 38
Annotation: disorder to order (Structural transition)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Most interestingly, the crystal structure of the 14-3-3σ/pHSPB6 complex also reveals the RLFDQxFG motif (HSPB6 residues 27–34), which is the sole highly conserved region within the NTD of vertebrate sHSPs (Heirbaut et al., 2014). We have found that in the type I chain this motif becomes ordered upon its insertion into the distinct shared groove of the ACD dimer formed by the two β3 strands (Bagneris et al., 2009) (Figures 3B and 3D).
Ordering of the NTDs within the 14-3-3/pHSPB6 complex follows the principle of induced folding, which appears to be a general feature observed upon the interaction of IDR-containing proteins with their partners (Wright and Dyson, 2009).
Cross-references: PDB:5LTW
Protein: DP01131 (UniProt O14558)
Region: residues 2	to 10
Annotation: self-interaction (Disorder function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
Interestingly, we have found that the type I N terminus “patches” the β4/β8 groove on the side of the nearest ACD within one heterotetramer, whereas the type II chain engages in a similar patching across a crystal lattice contact (Figures 3A and S2). In each case, residues V5 and V7 insert into the hydrophobic core of the ACD (Figure 3C). Moreover, we could obtain an independent insight into this phenomenon by co-crystallizing the isolated ACD domain of HSPB6 (residues 72–149) with an N-terminal peptide of HSPB6, which corresponds to residues 2–10 (EIPVPVQPS, N-peptide). The resulting crystal structure at 2.6 Å resolution readily reveals the patching of the β4/β8 grooves at either side of the ACD dimer by well-ordered peptides (Figure 3C), fully confirming the patching mechanism observed in the 14-3-3σ/pHSPB6 complex (Figure S2C).
Cross-references: PDB:5LUM
Protein: DP01131 (UniProt O14558)
Region: residues 13	to 20
Annotation: 14-3-3 protein binding (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
First, both phosphoserine-containing regions of the HSPB6 dimer were found to bind in the corresponding 14-3-3 grooves (Figure 3A), in a conformation virtually identical to that observed in the 14-3-3/phosphopeptide 13–20 complex (Cα RMSD of 0.15 Å for residues 14–19). The observed structure thus confirms the hypothesis that HSPB6 fully sequesters the 14-3-3 dimer, making it unavailable for interaction with other phosphorylated partners.
Figure 6. Proposed Mechanism of the 14-3-3/pHSPB6 Regulatory Complex Formation

Key regions of the HSPB6 NTD are labeled as follows: N, the N-terminal region (residues 1–10); P, the 14-3-3-binding region (residues 13–20) including the phosphoserine 16; C, the “central” conserved region (residues 27–34).
Cross-references: PDB:5LTW
Protein: DP01131 (UniProt O14558)
Region: residues 27	to 34
Annotation: self-interaction (Disorder function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
Most interestingly, the crystal structure of the 14-3-3σ/pHSPB6 complex also reveals the RLFDQxFG motif (HSPB6 residues 27–34), which is the sole highly conserved region within the NTD of vertebrate sHSPs (Heirbaut et al., 2014). We have found that in the type I chain this motif becomes ordered upon its insertion into the distinct shared groove of the ACD dimer formed by the two β3 strands (Bagneris et al., 2009) (Figures 3B and 3D).
Figure 6. Proposed Mechanism of the 14-3-3/pHSPB6 Regulatory Complex Formation

Key regions of the HSPB6 NTD are labeled as follows: N, the N-terminal region (residues 1–10); P, the 14-3-3-binding region (residues 13–20) including the phosphoserine 16; C, the “central” conserved region (residues 27–34). One of the two central regions may occupy the shared β3/β3 groove of the ACD dimer already in the free state.
Key regions of the HSPB6 NTD are labeled as follows: N, the N-terminal region (residues 1–10); P, the 14-3-3-binding region (residues 13–20) including the phosphoserine 16; C, the “central” conserved region (residues 27–34).
Cross-references: PDB:5LTW
Protein: DP01132 (UniProt Q12778)
Region: residues 242	to 266
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
"electron density was not observed for the C-terminal wing 2 region of the FoxO1 DBD suggesting that it is flexible and disordered in the crystals."
"we crystallized and determined the structure of FoxO1 151–266 bound to the IRE and DBE2 sequences, but electron density was not observed for residues 242–266."
Cross-references: PDB:3CO6
Protein: DP01132 (UniProt Q12778)
Region: residues 242	to 266
Annotation: nucleic acid binding (Molecular function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
"wing 2 enhances affinity through forming transient and/or multiple nonspecific electrostatic interactions with the phosphate backbone of the DNA. This hypothesis is supported by the observation that acetylation of Lys245 and Lys248 in wing 2 by CBP/p300 reduces DNA binding affinity"
Protein: DP01132 (UniProt Q12778)
Region: residues 246	to 262
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
"the lack of electron density at the C-terminal second wing (W2) indicates its flexibility and disorderness in FoxO1. Although we used the entire FoxO1-DBD (amino acids 154–262) in crystallization, the final electron density was only visible for the regions between amino acid 160 and 245 for both monomers."
Cross-references: PDB:5DUI
Protein: DP01133 (UniProt Q00987-11)
Region: residues 216	to 302
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Experimental NMR chemical shifts and 15N relaxation data demonstrate that Mdm2(216-302) is an intrinsically unstructured and highly flexible monomeric protein in solution, as confirmed by static light scattering analysis.
Protein: DP01133 (UniProt Q00987-11)
Region: residues 216	to 302
Annotation: protein binding (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
This acidic region of Mdm2 forms a fuzzy complex with a short sequence encompassing the alternatively spliced exon 3 (Ex3) of Numb.
Protein: DP01133 (UniProt Q00987-11)
Region: residues 216	to 302
Annotation: protein binding (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Our NMR data demonstrate that the Numb-Mdm2 binding interface comprises residues 216-302 of the Mdm2 acidic domain.
Protein: DP01134 (UniProt P10071)
Region: residues 106	to 236
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The NMR spectrum of Gli3RD expressing cells (Fig. 2A) is qualitatively similar to that of the purified protein, measured at pH 7.4 (Fig. 2B). All of the proton peaks lie within a narrow window of 8 ppm that is typical for unfolded peptides.
Protein: DP01135 (UniProt P40019)
Region: residues 1	to 153
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
Chz1 alone yielded a typical CD spectrum characteristic of an unfolded polypeptide chain, suggesting that Chz1 is unfolded in physiological conditions.
Protein: DP01136 (UniProt P22470)
Region: residues 1	to 610
Annotation: disorder (Structural state)
Evidence: gel electrophoresis evidence used in manual assertion
Supporting statements:
We also observed that intact San1 migrated at ~100 kDa, larger than its calculated ~66 kDa mass. Intrinsically disordered proteins often show this behavior due to a low content of hydrophobic residues (Tompa, 2002).
Protein: DP01136 (UniProt P22470)
Region: residues 1	to 610
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
The CD spectrum of San1 had a minimum close to 200 nm (Figure 2E), which is characteristic of a protein with mostly random coil content and is typical for intrinsically disordered proteins (Receveur-Brechot et al., 2006). 
The San1 spectrum had a small valley at ~224 nm indicating San1 possesses some α-helical content.
Protein: DP01136 (UniProt P22470)
Region: residues 1	to 610
Annotation: disorder (Structural state)
Evidence: gel-filtration evidence used in manual assertion
Supporting statements:
In light of the disorder predictions, we repeated the gel filtration assay using San1 purified from E. coli and found that San1 migrated at ~500 kDa despite the absence of any yeast proteins (Figure 2C), indicating that San1 is either disordered and/or forms multimers with itself. To examine if San1 forms multimers, we coexpressed differently tagged versions of San1 in E. coli and found that neither version copurified with the other (E.K.F. and R.G.G., unpublished data), indicating that San1 does not self-associate.
Protein: DP01136 (UniProt P22470)
Region: residues 1	to 610
Annotation: disorder (Structural state)
Evidence: cleavage assay evidence used in manual assertion
Supporting statements:
We found San1 was completely digested at the earliest time points whereas BSA resisted digestion throughout the time course of protease treatment (Figure 2D).
Protein: DP01136 (UniProt P22470)
Region: residues 1	to 610
Annotation: denatured protein binding (Molecular function)
Evidence: co-immunoprecipitation evidence used in manual assertion
Supporting statements:
The San1 substrate Sir4-9 had the greatest number of spectral counts in the tagged coIP replicates and showed the greatest enrichment over the untagged replicates.
Authors shows SAN1 only binds to Sir4, when the latter is mutated to a temperature-sensitive version and is induced to unfold, and not to the native wildtype protein.
Protein: DP01136 (UniProt P22470)
Region: residues 1	to 164
Annotation: denatured protein binding (Molecular function)
Evidence: yeast 2-hybrid evidence used in manual assertion
Supporting statements:
To test this, we fused to the Gal4 DNA-binding domain (GBD) a ubiquitination-deficient version of San1, which contains the C279S substitution in the RING domain (Gardner et al., 2005). We also fused the Gal4 activation domain (GAD) to either normal or mutant Sir4, Cdc68, and Cdc13.
As anticipated, we observed an interaction between San1 and mutant Sir4-9, Cdc68-1, and Cdc13-1 but not with normal Sir4, Cdc68, and Cdc13 (Figure 1A).
Authors shows SAN1 only binds to Sir4, when the latter is mutated to a temperature-sensitive version and is induced to unfold, and not to the native wildtype protein.
As expected, the RING domain deletion (residues 165-285) had little effect on substrate interactions consistent with its primary function in ubiquitin conjugase recruitment. In agreement with the second model, no single interaction profile emerged for San1-substrate interactions; multiple deletions in the N- and C-terminal disordered regions differentially affected each substrate interaction with San1 having a distinct interaction profile with each substrate.
Protein: DP01136 (UniProt P22470)
Region: residues 286	to 610
Annotation: denatured protein binding (Molecular function)
Evidence: yeast 2-hybrid evidence used in manual assertion
Supporting statements:
To test this, we fused to the Gal4 DNA-binding domain (GBD) a ubiquitination-deficient version of San1, which contains the C279S substitution in the RING domain (Gardner et al., 2005). We also fused the Gal4 activation domain (GAD) to either normal or mutant Sir4, Cdc68, and Cdc13.
As anticipated, we observed an interaction between San1 and mutant Sir4-9, Cdc68-1, and Cdc13-1 but not with normal Sir4, Cdc68, and Cdc13 (Figure 1A).
Authors shows SAN1 only binds to Sir4, when the latter is mutated to a temperature-sensitive version and is induced to unfold, and not to the native wildtype protein.
As expected, the RING domain deletion (residues 165-285) had little effect on substrate interactions consistent with its primary function in ubiquitin conjugase recruitment. In agreement with the second model, no single interaction profile emerged for San1-substrate interactions; multiple deletions in the N- and C-terminal disordered regions differentially affected each substrate interaction with San1 having a distinct interaction profile with each substrate.