LiteFold/DisProt huggingface dataset:
Protein: DP00070 (UniProt P37840)
Region: residues 1	to 102
Annotation: disorder to order (Structural transition)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
Our observations indicate a partition of αS into two functionally distinct regions. The N-terminal region is responsible for lipid binding. The NMR data suggest that the boundary for this region occurs between residues 102 and 103. Interestingly, the first three exons in the coding region of the αS gene encode residues 1 to 102, and a recent report indicates that the lipid binding capacity of αS is distributed across this region of the protein (Perrin et al., 2000). The close correspondence between the exon-defined boundary and the boundary we observe in our NMR data supports a distinct functional role (lipid binding) for this region of αS.
CD data (Figure 4) confirm that αS undergoes a large conformational transition to an α-helical state in the presence of SDS micelles, as it does in the presence of lipid vesicles, confirming that the protein interacts with the micelles, possibly in a similar fashion.
Far-UV CD data from wild-type αS in the presence and absence of SDS micelles, under conditions and protein concentrations (100 μM) identical to those used in the NMR experiments. A large conformational change is evident, with a high degree of helicity (indicated by the characteristic double minima at 208 and 222 nm) formed in the presence of micelles.
Thus, it appears that the interaction of αS with synthetic lipid vesicles is quite similar to its interaction with SDS detergent micelles, as nearly identical regions of the protein remain free from or are bound to the micelle or vesicle in both cases.
Protein: DP00070 (UniProt P37840)
Region: residues 1	to 103
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
To attempt to observe NMR resonances from the remaining, N-terminal 102 residues of αS, we raised the temperature of our sample from 10 to 40 °C. At this temperature, we observe a greater number of residues than at 10 °C, as shown in Figure 6. An examination of these resonances shows that they do not, in general correspond to resonances observed for either the free protein, or the protein in the presence of micelles at 10 °C. The number of backbone resonances visible is more than 100, suggesting that these resonances include the missing N-terminal resonances not observed at 10 °C. Many resonances from the free C-terminal portion of the protein are no longer observed, probably because at this temperature, the exchange of the backbone amide protons (which are unprotected in this unfolded segment of the protein) with solvent protons is far more rapid than at the lower temperature, and leads to the broadening of these signals.
Protein: DP00070 (UniProt P37840)
Region: residues 101	to 140
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Although the C-terminus is more dynamically constrained in fibrils and in α-syn bound to TOCL:DOPC vesicles, a direct comparison of carbon chemical shifts detected using through bond two-dimensional spectroscopy indicates that the C-terminus is flexible and unstructured in all the three samples.

The detected backbone chemical shifts indicate that the C-terminus is unstructured when bound to DOPA:DOPC lipid vesicles (Figure S1), in agreement with previous solution and solid-state NMR data (Ulmer et al. 2005; Fusco et al. 2014).
Protein: DP00071 (UniProt P23441)
Region: residues 1	to 156
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
In fact, under these experimental conditions, the CD trace lacks the characteristic local minima at 208/222 nm (Figure 2, spectrum a).
Protein: DP00071 (UniProt P23441)
Region: residues 1	to 156
Annotation: disorder to order (Structural transition)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
The addition of TFE significantly alters the structure of the N domain.
The amount of induced secondary structure reaches a plateau between 40 and 50% TFE.
Protein: DP00071 (UniProt P23441)
Region: residues 58	to 78
Annotation: disorder to order (Structural transition)
Evidence: cleavage assay evidence used in manual assertion
Supporting statements:
In the presence of 50% TFE, TTF-1 N domain is almost undigested (lane 3), confirming the evidence of gain of secondary structure (α-helix) obtained from CD studies.
The fragment of approx. 2 kDa was eluted from gel and subjected to N-terminal protein sequencing. The sequence identifies a fragment of 20 residues between residues 58 and 78 (Figure 1, left-hand panel, boxed).
Protein: DP00071 (UniProt P23441)
Region: residues 1	to 156
Annotation: disorder (Structural state)
Evidence: cleavage assay evidence used in manual assertion
Supporting statements:
The SDS/PAGE analysis of the proteolysis mixture after 6 h reaction at 25 °C (Figure 3) reveals that, in the absence of TFE, the TTF-1 N domain is completely digested by thermolysin into small peptides which are not stained by Coomassie Blue (lane 2).
Protein: DP00071 (UniProt P23441)
Region: residues 1	to 156
Annotation: transcription coactivator activity (Molecular function)
Evidence: transcriptional activation assay evidence used in manual assertion
Supporting statements:
Therefore these data indicate that the TTF-1 N domain is able to efficiently activate transcription in yeast, a property typical of acidic activation domains.
Protein: DP00071 (UniProt P23441)
Region: residues 1	to 156
Annotation: protein binding (Molecular function)
Evidence: bait-prey hybrid interaction evidence used in manual assertion
Supporting statements:
As shown in Figure 7(A), only the N domain was able to retain TBP. This interaction is specific, as confirmed by the SDS/PAGE shown in Figure 7(B), which demonstrates that only the TBP band (arrow) is enriched after elution.
Protein: DP00072 (UniProt Q8WZ42)
Region: residues 9880	to 12031
Annotation: disorder (Structural state)
Evidence: atomic force microscopy evidence used in manual assertion
Supporting statements:
The PEVK domain of the giant muscle protein titin is a proline-rich sequence with unknown secondary/tertiary structure. 
It is still debated whether the PEVK domain adopts a specific secondary/tertiary structure.
Protein: DP00072 (UniProt Q8WZ42)
Region: residues 9880	to 12031
Annotation: entropic chain (Disorder function)
Evidence: atomic force microscopy evidence used in manual assertion
Supporting statements:
The analysis revealed that cardiac PEVK titin acts as an entropic spring with the properties of a random coil exhibiting mechanical conformations of different flexibility.
Protein: DP00072 (UniProt Q8WZ42)
Region: residues 9880	to 12031
Annotation: protein binding (Molecular function)
Evidence: atomic force microscopy evidence used in manual assertion
Supporting statements:
Thus, the results may be interpreted to indicate binding of the constitutively expressed PEVK segment (“cardiac PEVK”) to actin filaments in both cardiac and skeletal muscle. In contrast, PEVK sequences present only in skeletal titins may exhibit little actin-binding propensity.
Protein: DP00072 (UniProt Q8WZ42)
Region: residues 11045	to 11070
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
In all of the chemically synthesized and expressed peptides, unordered coils were the major secondary structure identified.
Circular dichroism (CD) experiments demonstrated that both the positively charged PPAK modules and the negatively charged PolyE repeats had similar spectral properties with disordered secondary structure predominating.
Protein: DP00073 (UniProt P04818)
Region: residues 1	to 25
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The N terminus is largely disordered; good density starts at Pro-26, and this region does not change between hTS, NTE-hTS, and an inhibitory ternary complex of hTS with dUMP and Tomudex (ZD1694 or raltitrexed) (4) or analogous rat TS complex (PDB entry 2tsr(3)).
Cross-references: PDB:1HW3
PDB:1HW4
Protein: DP00073 (UniProt P04818)
Region: residues 107	to 128
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Region 107–128, which includes the insert, is disordered in the crystals.
Cross-references: PDB:1HW3
PDB:1HW4
Protein: DP00073 (UniProt P04818)
Region: residues 1	to 27
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The search model did not include 27 residues at the amino terminus, and two insertions of 12 and 8 amino acids residues that are highly conserved in eukaryotic species of TS at residues 90 (hi 17) to 101 (hi28), and inserted between 156 and 157 (h 146—hi52) respectively (Perry et al., 1990).
Protein: DP00073 (UniProt P04818)
Region: residues 117	to 128
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The highly conserved, but eukaryote-specific insertion of twelve residues 90—101 (hi 17—128), and of eight residues between 156 and 157 (hl46—hl53) are known to be a-helical in other eukaryotes, and lie close together on the outside of the protein in regions of disordered electron density in this crystal form.
The search model did not include 27 residues at the amino terminus, and two insertions of 12 and 8 amino acids residues that are highly conserved in eukaryotic species of TS at residues 90 (hi 17) to 101 (hi28), and inserted between 156 and 157 (h 146—hi52) respectively (Perry et al., 1990).
Protein: DP00074 (UniProt P03372)
Region: residues 1	to 184
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
A random coil sequence yields a very typical CD spectrum, with a sharp negative minimum at 198 nm. The recorded CD spectra of ERα-N and ERβ-N both show this characteristic profile (Figs. 5 and 6). The CD data therefore strengthen the conclusion from NMR that the ERα-N and ERβ-N fragments are unstructured in solution.
Protein: DP00074 (UniProt P03372)
Region: residues 1	to 184
Annotation: disorder to order (Structural transition)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
The most likely cause for the observed effect is that the structured TBP induces a folding event in the unstructured ERα-N transactivation region.
Protein: DP00074 (UniProt P03372)
Region: residues 1	to 184
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The HSQC spectra of ERα-N recorded in buffers with a neutral or basic pH contain very few and weak signals compared with the spectra recorded in buffers with acidic pH (data not shown). Likewise, backbone amide NMR signals decrease significantly as the temperature is increased from 5 to 20 °C (data not shown). Both effects reflect significant hydrogen exchange between amide protons and water at higher temperature and pH in the absence of stable intramolecular hydrogen bonds.
Protein: DP00074 (UniProt P03372)
Region: residues 214	to 236
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Superpositions onto the appropriate average structure were made using the Ca, N and C atoms of residues 4-35 and 59-74, since the backbone conformation at the termini and between residues 36 and 58 is comparatively poorly defined by the NMR data.
The residues 36-58 of the peptide analized by the autors corresponds to the 214-236 region of the protein.
Cross-references: PDB:1HCP
Protein: DP00074 (UniProt P03372)
Region: residues 253	to 262
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Superpositions onto the appropriate average structure were made using the Ca, N and C atoms of residues 4-35 and 59-74, since the backbone conformation at the termini and between residues 36 and 58 is comparatively poorly defined by the NMR data.
The residues 75-84 of the peptide analized by the autors, which lacks structure, corresponds to the 252-261 region of the protein.
Cross-references: PDB:1HCP
Protein: DP00074 (UniProt P03372)
Region: residues 1	to 184
Annotation: TBP-class protein binding (Molecular function)
Evidence: surface plasmon resonance evidence used in manual assertion
Supporting statements:
Fig. 3 Aillustrates the injection of purified yTBP over the surfaces captured with ΕRα-N (solid line) and ERβ-N (dotted line), respectively. The sensogram clearly shows binding of TBP to ERα-N but no significant binding to ERβ-N. 
TBP is a key protein of the transcription machinery and has been proposed as a target factor for a number of transcriptional activators.
Protein: DP00074 (UniProt P03372)
Region: residues 287	to 305
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The main chain structure of ER(287–305) in the absence of CaM is unstructured, although it adopts an α-helical structure upon binding to CaM (Fig. 2).
Protein: DP00074 (UniProt P03372)
Region: residues 287	to 305
Annotation: disorder to order (Structural transition)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The main chain structure of ER(287–305) in the absence of CaM is unstructured, although it adopts an α-helical structure upon binding to CaM (Fig. 2).
Cross-references: PDB:2LLO
PDB:2LLQ
Protein: DP00074 (UniProt P03372)
Region: residues 287	to 305
Annotation: calmodulin binding (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The main chain structure of ER(287–305) in the absence of CaM is unstructured, although it adopts an α-helical structure upon binding to CaM (Fig. 2).
Cross-references: PDB:2LLO
PDB:2LLQ
Protein: DP00074 (UniProt P03372)
Region: residues 300	to 304
Annotation: methylation display site (Disorder function)
Evidence: mass spectrometry evidence used in manual assertion
Supporting statements:
Recombinant SET7 methylated an ER peptide encompassing amino acids 294-314 of the hinge region, whereas two other histone H3 lysine 9-specific HMTases, G9a and Dim-5, did not (Figure 1B). In contrast, all three enzymes were able to methylate a histone H3 peptide (amino acids 1-24), suggesting that the methylation of the ER peptide by SET7 is specific.
Subsequent MS/MS analysis identified lysine 302 (K302) as the single site of methylation (Figure S1C).
Taken together, these data indicate that SET7-mediated methylation modulates the stability of ER and this effect is mediated through modification at K302.
Protein: DP00074 (UniProt P03372)
Region: residues 300	to 305
Annotation: methylation display site (Disorder function)
Evidence: qualitative western immunoblotting evidence used in manual assertion
Supporting statements:
Methylated ER was detected in cells expressing wild-type ER, but not the ER-K302R mutant (Figure 2A).
These data indicate that ER is methylated at K302 in vivo, and that the neighboring lysine, K303, impacts methylation of K302 by SET7.
Taken together, these data indicate that SET7-mediated methylation modulates the stability of ER and this effect is mediated through modification at K302.
Protein: DP00074 (UniProt P03372)
Region: residues 1	to 180
Annotation: 14-3-3 protein binding (Molecular function)
Evidence: glutathione S-transferase pull-down assay evidence used in manual assertion
Supporting statements:
Results showed that 14-3-3β bound to the AF-1 domain of ERα; however, the DBD and AF-2 domains did not bind to 14-3-3β (Fig. 2C).
 These results indicate that 14-3-3β interacts with ERα through the AF-1 domain of ERα in a ligand-dependent manner and Akt phosphorylation is critical in this event.
Protein: DP00074 (UniProt P03372)
Region: residues 301	to 305
Annotation: acetylation display site (Disorder function)
Evidence: in vitro acetylation assay evidence used in manual assertion
Supporting statements:
As expected, autoacetylation of GST-p300 was seen in all of the lanes, and WT ERα was efficiently and selectively acetylated by p300. In contrast, all of the K303 substitutions were hypoacetylated.
Protein: DP00074 (UniProt P03372)
Region: residues 301	to 305
Annotation: phosphorylation display site (Disorder function)
Evidence: loss-of-function mutant phenotype evidence used in manual assertion
Supporting statements:
We found that the S294A mutation had little effect on ERα phosphorylation but that the S305D mutation greatly reduced the phosphorylation of the ERα fragment.
Protein: DP00075 (UniProt P11387)
Region: residues 1	to 174
Annotation: disorder (Structural state)
Evidence: near-UV circular dichroism evidence used in manual assertion
Supporting statements:
Taking all of the information into account, gel filtration, sedimentation, and CD analyses, we conclude that the amino-terminal 174 resides of Topo I are largely unfolded and are comprised of very little if any extended secondary structure.
Protein: DP00075 (UniProt P11387)
Region: residues 652	to 696
Annotation: disorder (Structural state)
Evidence: cleavage assay evidence used in manual assertion
Supporting statements:
Evidence from limited proteolysis studies (see accompanying paper(40)) indicates that the former possibility is more likely to be correct. For example limited trypsin digestion of full-length Topo I generates a proteolytically resistant 55-kDa fragment that starts at residue Lys654 and ends somewhere very close to residue Lys654 (Fig. 1A in (40)).
Protein: DP00075 (UniProt P11387)
Region: residues 636	to 712
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The side chains of Lys436, His632, and Asn722 and the main chain amide nitrogens of Asn491, Gln633, and Ala635 make contacts closer than 3.5 Å in this complex but not in the covalent complex (Fig. 4G; note that residues 628 to 635 are disordered and are not present in the structure of the covalent complex).
Cross-references: PDB:1A31
Protein: DP00075 (UniProt P11387)
Region: residues 636	to 712
Annotation: flexible linker (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Thus, residues ∼636 to 712, which form the so-called linker domain, contribute to but are not required for activity (16).
Protein: DP00075 (UniProt P11387)
Region: residues 175	to 214
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The ∼210-residue NH2-terminal region of human topo I is highly charged, contains very few hydrophobic amino acids, and is largely disordered (12).
Cross-references: PDB:1A35
PDB:1A31
Protein: DP00075 (UniProt P11387)
Region: residues 628	to 719
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The only significant differences between the structures occur in the active-site region (as discussed below); in addition, residues 628 to 635 of subdomain III and 715 to 719 of the COOH-terminal domain are ordered in the noncovalent complex but are disordered in the covalent complex.
Cross-references: PDB:1A35
Protein: DP00075 (UniProt P11387)
Region: residues 1	to 174
Annotation: disorder (Structural state)
Evidence: cleavage assay evidence used in manual assertion
Supporting statements:
While designing the purification scheme, we noticed that long term storage of nuclear extracts leads to proteolysis of the full-length enzyme into a fragments of 75 and 70 kDa, designated f-Topo75 and f-Topo70, respectively (Fig. 2B, lanes 4 and 5). 
Amino terminal sequencing confirmed that f-Topo75 was missing the first 137 residues while f-Topo70 was missing the first 174 residues.
Protein: DP00075 (UniProt P11387)
Region: residues 1	to 174
Annotation: DNA binding, bending (Molecular function)
Evidence: DNA detection assay evidence used in manual assertion
Supporting statements:
In agreement with this finding, an N-terminal fragment of human topo I (amino acids 1–218) binds DNA in a filter binding assay (Fig. 3 B). Taken together, the obtained results suggest a role of the N-terminal domain or at least part of it in non-covalent DNA binding.
Protein: DP00075 (UniProt P11387)
Region: residues 1	to 174
Annotation: DNA binding (Molecular function)
Evidence: DNA detection assay evidence used in manual assertion
Supporting statements:
In agreement with this finding, an N-terminal fragment of human topo I (amino acids 1–218) binds DNA in a filter binding assay (Fig. 3 B). Taken together, the obtained results suggest a role of the N-terminal domain or at least part of it in non-covalent DNA binding.
Protein: DP00075 (UniProt P11387)
Region: residues 1	to 214
Annotation: molecular condensate scaffold activity (Molecular function)
Evidence: fluorescence recovery after photobleaching evidence used in manual assertion
Supporting statements:
Condensation of the N-terminal domain of human topoisomerase 1 is driven
by electrostatic interactions and tuned by its charge distribution
hTOP1 forms liquid condensates in vivo
 Here, we investigated the ability of hTOP1 to form liquid condensates by transiently expressing exogenous GFP-tagged hTOP1 in HeLa cells. In our cellular model, hTOP1 indeed forms nucleoplasmatic and nucleolar condensates, giving rise to a sparse punctuate pattern (Fig. 1A). Notably, these condensates exhibit a liquid-like behavior, as indicated by FRAP analyses, with a full fluorescence recovery within 80 s (Fig. 1B). In light of the well- established role of IDRs in LLPS, we reasoned that the formation of hTOP1 condensates might be primarily driven by its hNTD (residues 1–214), which has been identified as intrinsically disordered [39].
Protein: DP00075 (UniProt P11387)
Region: residues 1	to 214
Annotation: molecular condensate scaffold activity (Molecular function)
Evidence: turbidity measurement evidence used in manual assertion
Supporting statements:
We found that protein concentration influenced the maximum turbidimetry value but not its kinetics (Fig. 3A). To investigate whether electrostatic charges drove the protein condensation, we performed the pH jump in the presence of increasing salt concentrations, which can inhibit electrostatic interactions. We observed a significant decrease in turbidity at 150 mM and 300 mM of NaCl (Fig. 3A), indicating the crucial role of electrostatic interactions in hNTD condensation. Since turbidimetry alone does not specifically confirm LLPS and could be ascribable to the formation of amorphous/fibrillar aggregates, confocal microscopic analyses were conducted to identify LLPS hall­ marks: spherical shape, the ability to undergo fusion events, and liquid- like behavior [41].