LiteFold/DisProt huggingface dataset:
Protein: DP02851 (UniProt Q5FWF5)
Region: residues 1	to 15
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The PDB shows this region lacks electron density, indicating it is disordered.
Cross-references: PDB:5T53
Protein: DP02852 (UniProt P55197)
Region: residues 179	to 188
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The first PHD finger adopts a mixed α/β fold characteristic of canonical PHD fingers, while PHD finger 2 is atypical and is composed solely of six α-helical segments with a disordered segment spanning residues 179–188 (Figure S2A).
A segment within PHD finger 2 of AF10PZP, that spans amino acids 179-188, is disordered in the 1.60 Å structure in the free state (Figure S2A). Upon complex formation with H3(1-36) peptide, this region becomes ordered to form an anti-parallel β-sheet (Figure 2I, marked by arrow; free and bound structures superimposition shown in Figure S2D). This dynamic β-sheet forms part of the binding channel wall within the PZP domain and contributes to the alignment of the bound H3 peptide with residue E179, which emanates from this β-sheet platform, directly involved in recognition of the ε-NH3+ group of K23 (Figure 2E).
Cross-references: PDB:5DAG
Protein: DP02852 (UniProt P55197)
Region: residues 179	to 190
Annotation: protein binding (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
The first PHD finger adopts a mixed α/β fold characteristic of canonical PHD fingers, while PHD finger 2 is atypical and is composed solely of six α-helical segments with a disordered segment spanning residues 179–188 (Figure S2A).
A segment within PHD finger 2 of AF10PZP, that spans amino acids 179-188, is disordered in the 1.60 Å structure in the free state (Figure S2A). Upon complex formation with H3(1-36) peptide, this region becomes ordered to form an anti-parallel β-sheet (Figure 2I, marked by arrow; free and bound structures superimposition shown in Figure S2D). This dynamic β-sheet forms part of the binding channel wall within the PZP domain and contributes to the alignment of the bound H3 peptide with residue E179, which emanates from this β-sheet platform, directly involved in recognition of the ε-NH3+ group of K23 (Figure 2E).
Cross-references: PDB:5DAH
Protein: DP02852 (UniProt P55197)
Region: residues 179	to 190
Annotation: histone H3-K27 methylation (Biological process)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
The first PHD finger adopts a mixed α/β fold characteristic of canonical PHD fingers, while PHD finger 2 is atypical and is composed solely of six α-helical segments with a disordered segment spanning residues 179–188 (Figure S2A).
A segment within PHD finger 2 of AF10PZP, that spans amino acids 179-188, is disordered in the 1.60 Å structure in the free state (Figure S2A). Upon complex formation with H3(1-36) peptide, this region becomes ordered to form an anti-parallel β-sheet (Figure 2I, marked by arrow; free and bound structures superimposition shown in Figure S2D). This dynamic β-sheet forms part of the binding channel wall within the PZP domain and contributes to the alignment of the bound H3 peptide with residue E179, which emanates from this β-sheet platform, directly involved in recognition of the ε-NH3+ group of K23 (Figure 2E).
In cells, PZP recognition of H3 is required for H3K79 dimethylation, expression of DOT1L-target genes, and proliferation of DOT1L-addicted leukemic cells. Together, our results uncover a pivotal role for H3K27-via readout by the AF10 PZP domain-in regulating the cancer-associated enzyme DOT1L.
Cross-references: PDB:5DAH
Protein: DP02852 (UniProt P55197)
Region: residues 1	to 23
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Missing electron density region at the N-terminus of the protein.
Cross-references: PDB:5DAG
Protein: DP02852 (UniProt P55197)
Region: residues 179	to 188
Annotation: disorder to order (Structural transition)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
A segment within PHD finger 2 of AF10PZP, that spans amino acids 179-188, is disordered in the 1.60 Å structure in the free state (Figure S2A). Upon complex formation with H3(1-36) peptide, this region becomes ordered to form an anti-parallel β-sheet (Figure 2I, marked by arrow; free and bound structures superimposition shown in Figure S2D).
Protein: DP02853 (UniProt Q99P68)
Region: residues 1	to 51
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
In this study we present the structure of murine Sclerostin by solution NMR spectroscopy revealing that only the cystin-knot motif is structured.
N- and C-termini of Sclerostin are flexible
We initially prepared full-length murine Sclerostin (mSOST) in Sf9 cells (Fig. 1A). The protein comprising Gln1 to Tyr188 could be obtained from the supernatant of Sf9 cells. Staining via the Periodic Schiff Acid method confirmed the presence of glycosylation; mass spectrometry subsequently showed both N-glycosylation sites, Asn28 and Asn150, to be linked to carbohydrates. Storage of full-length mSOST over several weeks at 4 °C resulted in partial proteolysis although the protein solution had a purity of ⩾95%. Thus residual protease activity cleaves mSOST indicating the presence of flexible regions. The largest fragment showed an apparent molecular weight of roughly 10–12 kDa in a SDS–PAGE analysis (Fig. 1B). Mass spectrometry gave a molecular weight of 10,254 Da, which corresponds to a fragment comprising Glu52 to Cys142.
To additionally test our hypothesis that the N- and C-terminus are highly flexible and unstructured we compared the 2D 1H–15N HSQC spectra of uniformly 15N-labeled full-length mSOST and mSOSTΔNC. Residues located in the termini of mSOST exhibit amide proton chemical shift values between 7.5 and 8.5 ppm indicative for random coil conformation (Supplementary Fig. 2).
Protein: DP02853 (UniProt Q99P68)
Region: residues 143	to 211
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
In this study we present the structure of murine Sclerostin by solution NMR spectroscopy revealing that only the cystin-knot motif is structured.
N- and C-termini of Sclerostin are flexible
We initially prepared full-length murine Sclerostin (mSOST) in Sf9 cells (Fig. 1A). The protein comprising Gln1 to Tyr188 could be obtained from the supernatant of Sf9 cells. Staining via the Periodic Schiff Acid method confirmed the presence of glycosylation; mass spectrometry subsequently showed both N-glycosylation sites, Asn28 and Asn150, to be linked to carbohydrates. Storage of full-length mSOST over several weeks at 4 °C resulted in partial proteolysis although the protein solution had a purity of ⩾95%. Thus residual protease activity cleaves mSOST indicating the presence of flexible regions. The largest fragment showed an apparent molecular weight of roughly 10–12 kDa in a SDS–PAGE analysis (Fig. 1B). Mass spectrometry gave a molecular weight of 10,254 Da, which corresponds to a fragment comprising Glu52 to Cys142.
To additionally test our hypothesis that the N- and C-terminus are highly flexible and unstructured we compared the 2D 1H–15N HSQC spectra of uniformly 15N-labeled full-length mSOST and mSOSTΔNC. Residues located in the termini of mSOST exhibit amide proton chemical shift values between 7.5 and 8.5 ppm indicative for random coil conformation (Supplementary Fig. 2).
Protein: DP02853 (UniProt Q99P68)
Region: residues 1	to 51
Annotation: disorder (Structural state)
Evidence: sodium dodecyl sulfate polyacrylamide gel electrophoresis evidence used in manual assertion
Supporting statements:
In this study we present the structure of murine Sclerostin by solution NMR spectroscopy revealing that only the cystin-knot motif is structured.
N- and C-termini of Sclerostin are flexible
We initially prepared full-length murine Sclerostin (mSOST) in Sf9 cells (Fig. 1A). The protein comprising Gln1 to Tyr188 could be obtained from the supernatant of Sf9 cells. Staining via the Periodic Schiff Acid method confirmed the presence of glycosylation; mass spectrometry subsequently showed both N-glycosylation sites, Asn28 and Asn150, to be linked to carbohydrates. Storage of full-length mSOST over several weeks at 4 °C resulted in partial proteolysis although the protein solution had a purity of ⩾95%. Thus residual protease activity cleaves mSOST indicating the presence of flexible regions. The largest fragment showed an apparent molecular weight of roughly 10–12 kDa in a SDS–PAGE analysis (Fig. 1B). Mass spectrometry gave a molecular weight of 10,254 Da, which corresponds to a fragment comprising Glu52 to Cys142.
To additionally test our hypothesis that the N- and C-terminus are highly flexible and unstructured we compared the 2D 1H–15N HSQC spectra of uniformly 15N-labeled full-length mSOST and mSOSTΔNC. Residues located in the termini of mSOST exhibit amide proton chemical shift values between 7.5 and 8.5 ppm indicative for random coil conformation (Supplementary Fig. 2).
Protein: DP02853 (UniProt Q99P68)
Region: residues 143	to 211
Annotation: disorder (Structural state)
Evidence: sodium dodecyl sulfate polyacrylamide gel electrophoresis evidence used in manual assertion
Supporting statements:
In this study we present the structure of murine Sclerostin by solution NMR spectroscopy revealing that only the cystin-knot motif is structured.
N- and C-termini of Sclerostin are flexible
We initially prepared full-length murine Sclerostin (mSOST) in Sf9 cells (Fig. 1A). The protein comprising Gln1 to Tyr188 could be obtained from the supernatant of Sf9 cells. Staining via the Periodic Schiff Acid method confirmed the presence of glycosylation; mass spectrometry subsequently showed both N-glycosylation sites, Asn28 and Asn150, to be linked to carbohydrates. Storage of full-length mSOST over several weeks at 4 °C resulted in partial proteolysis although the protein solution had a purity of ⩾95%. Thus residual protease activity cleaves mSOST indicating the presence of flexible regions. The largest fragment showed an apparent molecular weight of roughly 10–12 kDa in a SDS–PAGE analysis (Fig. 1B). Mass spectrometry gave a molecular weight of 10,254 Da, which corresponds to a fragment comprising Glu52 to Cys142.
To additionally test our hypothesis that the N- and C-terminus are highly flexible and unstructured we compared the 2D 1H–15N HSQC spectra of uniformly 15N-labeled full-length mSOST and mSOSTΔNC. Residues located in the termini of mSOST exhibit amide proton chemical shift values between 7.5 and 8.5 ppm indicative for random coil conformation (Supplementary Fig. 2).
Protein: DP02853 (UniProt Q99P68)
Region: residues 26	to 30
Annotation: glycosylation display site (Disorder function)
Evidence: mass spectrometry evidence used in manual assertion
Supporting statements:
Staining via the Periodic Schiff Acid method confirmed the presence of glycosylation; mass spectrometry subsequently showed both N-glycosylation sites, Asn28 and Asn150, to be linked to carbohydrates.
Protein: DP02853 (UniProt Q99P68)
Region: residues 148	to 152
Annotation: glycosylation display site (Disorder function)
Evidence: mass spectrometry evidence used in manual assertion
Supporting statements:
Staining via the Periodic Schiff Acid method confirmed the presence of glycosylation; mass spectrometry subsequently showed both N-glycosylation sites, Asn28 and Asn150, to be linked to carbohydrates.
Protein: DP02854 (UniProt Q9BYF1)
Region: residues 769	to 805
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Full-length ACE2 consists of an Nterminal PD and a C-terminal collectrin-like domain (CLD) that ends with a single transmembrane helix and a ~40-residue intracellular segment (15, 21).
The high resolution supported reliable model building. For ACE2, side chains could be assigned to residues 19 to 768, which contain the PD (residues 19 to 615) and the CLD (residues 616 to 768), which consists of a small extracellular domain, a long linker, and the single TM helix (Fig. 1C).
The C-terminal tail starting on residue 769 has no density in the structure and is therefore disordered
Cross-references: PDB:6M1D
PDB:6M17
PDB:6M18
Protein: DP02854 (UniProt Q9BYF1)
Region: residues 779	to 783
Annotation: phosphorylation display site (Disorder function)
Evidence: radioisotope assay evidence used in manual assertion
Supporting statements:
Using this new labeling strategy specifically tailored for phosphotyrosines, it was possible to generate the time profiles for 318 unique phosphopeptides belonging to 215 proteins from an erlotinib-treated breast cancer cell line model.
Protein: DP02855 (UniProt P11166)
Region: residues 456	to 492
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
In the GLUT1 structure, residues 9–455 constitute the canonical MFS fold whereas the C-terminal segment was invisible probably due to its inherent flexibility in this conformation (Fig. 1).
Cross-references: PDB:4PYP
Protein: DP02855 (UniProt P11166)
Region: residues 456	to 492
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
As in 4PYP, residues 1–8 and 456–504 were not visible in density maps and are not part of our structures.
Cross-references: PDB:5EQG
PDB:5EQH
PDB:5EQI
Protein: DP02856 (UniProt P83916)
Region: residues 73	to 107
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Here, we used NMR spectroscopy in combination with small angle X-ray scattering and dynamic light scattering to characterize the dynamic and structural properties of full-length human HP1β (hHP1β) in solution. We show that the hinge region is highly flexible and enables a largely unrestricted spatial search by the two globular domains for their binding partners
Besides the two structurally related CD (21–71) and CSD (110–170), the remainder of the protein, which accounts for more than one third of the sequence, has a non-globular character with a high percentage of charged residues. The non-globular nature of the hinge region and the N- and C-terminal tails lead to severe signal overlap between 8 and 8.5 ppm in the 1H dimension and a large dynamic range of peak intensities.
For most residues in the tails and the hinge region the absolute values of Cα secondary chemical shifts were below 0.3 ppm (figure 2C and, for the combined secondary chemical shifts see figure S1), supporting their intrinsically disordered nature. In the hinge region a weak helical tendency expands the α-helix of the CD beyond residue 70 up to 73. In addition, a continuous stretch of small negative Cα secondary shifts in proximity to residue 20 points to a propensity for extended conformations in the N-terminal tail. 

According to 15N spin relaxation rates the backbone outside of CD and CSD is highly mobile (figure 3).
The limits of the region are determined from the NMR data in Figures 2, 3 and 4
Protein: DP02856 (UniProt P83916)
Region: residues 73	to 107
Annotation: disorder (Structural state)
Evidence: small-angle X-ray scattering evidence used in manual assertion
Supporting statements:
Here, we used NMR spectroscopy in combination with small angle X-ray scattering and dynamic light scattering to characterize the dynamic and structural properties of full-length human HP1β (hHP1β) in solution. We show that the hinge region is highly flexible and enables a largely unrestricted spatial search by the two globular domains for their binding partners
Comparison of the R g distribution derived from the optimized ensembles with that obtained from a pool of randomly generated models is shown in figure 1D. The R g distribution of the selected ensemble is nearly as broad as the one from the initial random pool, with the maximum shifted towards longer distances, indicating that the hinge region is highly flexible with a preference for more extended conformations.
Protein: DP02856 (UniProt P83916)
Region: residues 73	to 107
Annotation: disorder (Structural state)
Evidence: dynamic light scattering assay evidence used in manual assertion
Supporting statements:
Here, we used NMR spectroscopy in combination with small angle X-ray scattering and dynamic light scattering to characterize the dynamic and structural properties of full-length human HP1β (hHP1β) in solution. We show that the hinge region is highly flexible and enables a largely unrestricted spatial search by the two globular domains for their binding partners
Dynamic light scattering measurements resulted in a well-defined monodisperse peak with a hydrodynamic radius of 4.4±0.1 nm (figure 1A). The value is in agreement with the results from pulse field gradient NMR (figure 1B) and indicates that the protein does not assume a compact state in solution.
Protein: DP02856 (UniProt P83916)
Region: residues 176	to 185
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Here, we used NMR spectroscopy in combination with small angle X-ray scattering and dynamic light scattering to characterize the dynamic and structural properties of full-length human HP1β (hHP1β) in solution. We show that the hinge region is highly flexible and enables a largely unrestricted spatial search by the two globular domains for their binding partners
The N- and C-terminal tails as well as the hinge region showed much smaller J(0) and bigger J(0.87ωH) than the two globular domains, indicating a very slow decay of their spectral density function characteristic of fast tumbling molecules with high internal mobility.
The J(0.87ωH) profile demonstrated that the N-terminal tail experiences smaller internal dynamics when compared to the hinge region, with the C-terminal tail being the most flexible part among the disordered domains (figure S3A).
The limits of the region are determined from the NMR data in Figures 2, 3 and 4
Protein: DP02856 (UniProt P83916)
Region: residues 176	to 185
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
No specific mention in text, but the region 176-185 is missing in the electron density
Cross-references: PDB:3Q6S
Protein: DP02856 (UniProt P83916)
Region: residues 73	to 107
Annotation: flexible linker (Disorder function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
We show that the hinge region is highly flexible and enables a largely unrestricted spatial search by the two globular domains for their binding partners.
Protein: DP02858 (UniProt P18206-2)
Region: residues 844	to 876
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The asymmetric unit contains two copies of the vinculin monomer and the proline-rich linker, speculated to function as a hinge for the protein Price et al. 1989, Brindle et al. 1996, was largely disordered.
The N- and C-terminal helical bundles are indicated. In one monomer in the asymmetric unit residues 853–872 are disordered, while residues 853-878 are disordered in the other monomer in the asymmetric unit. These residues span vinculin's proline-rich linker. For clarity, all figures of full-length vinculin show residues 1–840 and 879–1066.
However, disordered regions were difficult to parameterize in terms of multiple conformations at the given resolution, which led to relatively high B factor and R factor statistics for the single-conformation models used, and did limit the scope of reliably assigning bound water molecules.
Cross-references: PDB:1TR2
Protein: DP02858 (UniProt P18206-2)
Region: residues 857	to 879
Annotation: protein binding (Molecular function)
Evidence: isothermal titration calorimetry evidence used in manual assertion
Supporting statements:
As shown in Fig. 2B and C, similar dissociation constants (Kd) were obtained for vin857 (1.08 μM) and vin837 (1.16 μM) with the tandem SH3 domains, and the stoichiometries of vin857 and vin837 were both determined to be 1, indicating that vin857 is sufficient for the interaction.
Protein: DP02858 (UniProt P18206-2)
Region: residues 857	to 879
Annotation: protein binding (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Because no inter-domain NOEs are observed between the SH3a and SH3b domains after their binding to vin857 (data not shown), the enhanced binding affinity is most likely caused by the flexible linker, which tethers both the SH3a and SH3b domains and restricts the dissociation ability of the individual SH3 domains from the substrate.
Additionally, almost the same NMR chemical shift perturbations were observed in the 15N-HSQC spectra of the tandem SH3 domains upon titration with the vin837 and vin857 peptides (Fig. S3), consistent with the above-mentioned ITC results.
Protein: DP02858 (UniProt P18206-2)
Region: residues 857	to 867
Annotation: protein binding (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
In this study, we first determined the solution structure of the tandem SH3 domains of CAP and further analyzed its complex structure with the proline-rich linker of vinculin using ITC, NMR, and X-ray crystallography.
The binding motif of the SH3 domain of Vinculin (857-879) is composed of two short proline-rich regions (prr): prr1 (N- LAPPKPPLPE -C), corresponding to PDB:4ln2, and prr2 (N- VPPPRPPPPE -C), corresponding to PDB:4lnp.
Cross-references: PDB:4ln2
Protein: DP02858 (UniProt P18206-2)
Region: residues 870	to 879
Annotation: protein binding (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
In this study, we first determined the solution structure of the tandem SH3 domains of CAP and further analyzed its complex structure with the proline-rich linker of vinculin using ITC, NMR, and X-ray crystallography.
The binding motif of the SH3 domain of Vinculin (857-879) is composed of two short proline-rich regions (prr): prr1 (N- LAPPKPPLPE -C), corresponding to PDB:4ln2, and prr2 (N- VPPPRPPPPE -C), corresponding to PDB:4lnp.
Cross-references: PDB:4lnp
Protein: DP02858 (UniProt P18206-2)
Region: residues 870	to 879
Annotation: disorder to order (Structural transition)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
In this study, we first determined the solution structure of the tandem SH3 domains of CAP and further analyzed its complex structure with the proline-rich linker of vinculin using ITC, NMR, and X-ray crystallography.
The binding motif of the SH3 domain of Vinculin (857-879) is composed of two short proline-rich regions (prr): prr1 (N- LAPPKPPLPE -C), corresponding to PDB:4ln2, and prr2 (N- VPPPRPPPPE -C), corresponding to PDB:4lnp.
Cross-references: PDB:4lnp