LiteFold/DisProt huggingface dataset:
Protein: DP01817 (UniProt Q15910)
Region: residues 497	to 513
Annotation: histone binding (Molecular function)
Evidence: cryogenic electron microscopy evidence used in manual assertion
Supporting statements:
Fig. 2 Interaction of EZH2 with the histone H3 tail and nucleosomal DNA.
(A) (Top) Cartoon representation of the newly defined EZH2 bridge helix (amino acids 497 to 513) that interacts with nucleosomal DNA and the H3 tail. (Left) Cryo-EM structure of the PRC2-AEBP2-JARID2 complex bound to an H2AK119ub1-containing nucleosome. The zoom out shows the bridge helix, with residues interacting with the EZH2 (SET) domain, nucleosomal DNA, and the histone tail depicted in stick representation. (Right) Helix wheel diagram for the bridge helix that shows the distribution of positively charged residues on the nucleosomal DNA interacting face (cyan), positive and hydrophobic residues on the EZH2 (SET) interacting face (blue), and the residues interacting with the backbone of the H3 tail (pink). aa, amino acids.
(B) (Left) Density map of the histone H3 tail (amino acids 21 to 40) (contour level:0.024) with the corresponding atomic model.
Cross-references: PDB:6WKR
EMDB:EMD-21707
Protein: DP01817 (UniProt Q15910)
Region: residues 340	to 435
Annotation: disorder (Structural state)
Evidence: proton-based nuclear magnetic resonance evidence used in manual assertion
Supporting statements:
As
a result of the successful resonance assignment, the obtained chemical shift values indicate the
highly disordered nature of the EZH2 loop, with some nascent helical tendency in the Ser407–Ser412
region.
The signal dispersion of both 1HN and 1Hα dimensions is only ca. 1 ppm (Figure 2a,b), indicating a similar chemical environment for each residue (Figure 2b). This is already indicative of a protein without any defined structure.
Results show that the two predictors give a similar picture (Figure 3 and Figure S3a,b), with SCS values close to 0.0, and no expanded constant sign tendencies are observed. The only exception is the Ser407–Ser412 segment with a helical tendency, although, even in this case, SCS values are below 0.6 ppm. This suggests a highly disordered random coil nature with a short nascent helical motif at Ser407–Ser412.
Analysis of the determined chemical shifts experimentally proved the highly disordered
behavior of the EZH2 loop. An α-helical tendency is observed in the Ser408–Ser412
region, and the high disorder is maintained over a large temperature range. This lack of
transient structural elements is relatively uncommon even amongst IDPs. EZH2 maintains
its highly disordered state even when bound to RNA, and the nascent helical region does
not play any role in the interaction.
Cross-references: BMRB:51420
Protein: DP01817 (UniProt Q15910)
Region: residues 367	to 375
Annotation: RNA binding (Molecular function)
Evidence: proton-based nuclear magnetic resonance evidence used in manual assertion
Supporting statements:
The interaction and determination of the binding sites on the EZH2 loop was monitored by chemical shift mapping in the absence and presence of Mg2+. In both cases, the same result is obtained: the addition of RNA causes significant chemical shift perturbations in the Thr367–Ser375 region (Figure 5).
Protein: DP01825 (UniProt P25644)
Region: residues 422	to 469
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
 Some residues are not visible in the electron density map and assumed to be disordered. These include residues 81-89 in chains A and B, residues 49-55 and 94-95 in chain C, residues 50-58 and 94-95 in chain D, residues 48-59 and 81-89 in chain E, residues 53-56 and 80-89 in chain F, residues 49-55 and 94-95 in chain G, residues 422-469, 751-757 and 795-796 in chains H, I and J, respectively, and residue 794 in chain I.
Cross-references: PDB:4N0A
Protein: DP01825 (UniProt P25644)
Region: residues 5	to 24
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
No ordered electron density was present for residues 5–24 and 55–79 of Pat1, consistent with the results from the binding assays (Figure 1B, D and Supplementary Figure S1).
Cross-references: PDB:4BRW
Protein: DP01825 (UniProt P25644)
Region: residues 55	to 79
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
No ordered electron density was present for residues 5–24 and 55–79 of Pat1, consistent with the results from the binding assays (Figure 1B, D and Supplementary Figure S1).
Cross-references: PDB:4BRW
Protein: DP01832 (UniProt Q7Q3R9)
Region: residues 22	to 103
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
cE5 displayed a typical circular dichroism (CD) spectrum of an unstructured protein, with a minimum at 202 nm (Fig. 2)
Protein: DP01832 (UniProt Q7Q3R9)
Region: residues 22	to 103
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The 1H,15N HSQC spectrum of 15N- labeled cE5 showed a limited chemical shift range (Fig. 3A), indicative of an unfolded molecule having few secondary structure elements, consistent with the random-coil state suggested by CD data.
Protein: DP01832 (UniProt Q7Q3R9)
Region: residues 85	to 103
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
No significant density was present for the N-terminal tetrapeptide cE5(Asp-31) to cE5(Glu-34) or for the C-terminal 21 amino acids (cE5(Ser-64) to cE5(Glu-82) of the P5 fragment...
Cross-references: PDB:5NHU
Protein: DP01832 (UniProt Q7Q3R9)
Region: residues 56	to 84
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
...complex A comprising thrombin residues T(Ser-1E) to T(Arg-15) and T(Ile-16) to T(Gly-246) and inhibitor residues cE5(Glu-35) to cE5(Asn-63)...
Cross-references: PDB:5NHU
Protein: DP01832 (UniProt Q7Q3R9)
Region: residues 56	to 84
Annotation: disorder to order (Structural transition)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
In agreement with the results of CD (Fig. 2) and NMR measurements (Fig. 3), the inhibitor adopts a mostly extended conformation, running in a reverse orientation to substrates on the surface of thrombin and interacting with both the exosite I and the active-site region of the proteinase (Fig. 7, A, C, and D).
Protein: DP01832 (UniProt Q7Q3R9)
Region: residues 56	to 84
Annotation: protein binding (Molecular function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
...the cE5 fragment spanning residues cE5(Glu-35) to cE5(Asp-47) blocks the exosite I of the proteinase (Figs. 4 and 7C).
Protein: DP01832 (UniProt Q7Q3R9)
Region: residues 56	to 84
Annotation: molecular function inhibitor activity (Molecular function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Overall, the cE5 central region represented by the P2 peptide appeared as the main responsible for both thrombin binding and inhibition.
Protein: DP01833 (UniProt P85800)
Region: residues 1	to 32
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
CD spectra of s-variegin, EP25, and AP18 are all similar to that of n-variegin, typical of random-coil proteins (supplemental Fig. S2).
Protein: DP01833 (UniProt P85800)
Region: residues 8	to 32
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
CD spectra of s-variegin, EP25, and AP18 are all similar to that of n-variegin, typical of random-coil proteins (supplemental Fig. S2).
Protein: DP01833 (UniProt P85800)
Region: residues 11	to 32
Annotation: disorder (Structural state)
Evidence: cleavage assay evidence used in manual assertion
Supporting statements:
To investigate how the cleavage affects the activity, MH22, s- variegin, and hirulog-1 were preincubated with thrombin for different lengths of time before determination of their residual thrombin inhibitory activities (Table 1 and Figure 2A).
Protein: DP01833 (UniProt P85800)
Region: residues 15	to 32
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
CD spectra of s-variegin, EP25, and AP18 are all similar to that of n-variegin, typical of random-coil proteins (supplemental Fig. S2).
Protein: DP01833 (UniProt P85800)
Region: residues 12	to 28
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Only 17 out of the 32 residues (VHis12 to VLeu28) of s-variegin have well-defined density (Figure 1C).
Cross-references: PDB:3B23
Protein: DP01833 (UniProt P85800)
Region: residues 12	to 28
Annotation: protein binding (Molecular function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
In contrast, the C-terminal fragment MH22 V(11MHKTAPPFDFEAIPEEYLDDES32) remains bound to thrombin after cleavage.
Protein: DP01833 (UniProt P85800)
Region: residues 12	to 28
Annotation: disorder to order (Structural transition)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Only 17 out of the 32 residues (VHis12 to VLeu28) of s-variegin have well-defined density (Figure 1C).
Protein: DP01833 (UniProt P85800)
Region: residues 12	to 28
Annotation: molecular function inhibitor activity (Molecular function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
s-Variegin fits firmly into the canyon-like cleft extending from the thrombin active site to exosite-I.
Protein: DP01834 (UniProt Q6F3E8)
Region: residues 147	to 156
Annotation: protein binding (Molecular function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Thus, we built 2 segments of the peptide, representing the active site binding region N terminus to the scissile bond A(5QTAVPK10) and exosite-I binding region A(19DFEEIPSDEI28) (Fig. 5A, B).
Protein: DP01835 (UniProt O43715)
Region: residues 54	to 76
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
These were assigned to the C-terminus, and their elevated transverse 15N relaxation times, as evidenced by narrow line widths, indicate that the C-terminal region (after K53) is highly disordered and dynamic on a pico- to nanosecond timescale.
Cross-references: PDB:4XZS
Protein: DP01836 (UniProt O14713)
Region: residues 49	to 59
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
"In the KRIT1-ICAP1 co-crystal structure the ICAP1 construct spans residues 49 to 200 but the first residue visible in all copies of the asymmetric unit is C60-ICAP and the final well-ordered residue is Ser193-ICAP. "
Cross-references: PDB:4DX8
Protein: DP01836 (UniProt O14713)
Region: residues 49	to 59
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The crystal structure of  ICAP1(residues 49–200)–KRIT1(residues 170–198) has been solved. The first residue visible in the structure is C60.
Cross-references: PDB:4JIF
Protein: DP01837 (UniProt P37330)
Region: residues 300	to 310
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
This includes residues 3-722 with the exception of a surface loop from 300 to 310 for which the electron density is weak and essentially uninterpretable
Cross-references: PDB:1D8C
Protein: DP01838 (UniProt P68005)
Region: residues 1	to 13
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
"The N terminus is unstructured. "
"Two features are immediately obvious from the data: first, signal attenuations are very small for the N-terminal, unstructured segment. "
Cross-references: PDB:1RU5
Protein: DP01840 (UniProt P38968)
Region: residues 770	to 1100
Annotation: disorder (Structural state)
Evidence: cleavage assay evidence used in manual assertion
Supporting statements:
The low sequence complexity of the prolinerich segment and its sensitivity to proteolysis suggest that this region is largely unstructured and forms a flexible linker to the terminal a-solenoid and that the 55K region projects in toward the membrane to engage Sec23/24 (via a portion of the proline-rich segment)
Cross-references: PDB:4BZJ
Protein: DP01841 (UniProt P08514)
Region: residues 997	to 1008
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The C terminus of αIIb (R997-E1008) is rich in acidic residues and largely unstructured, as was observed previously
Protein: DP01842 (UniProt P05106)
Region: residues 741	to 788
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
In aqueous solution, the αIIb and β3 tails are largely unstructured, although part of the β3 tail has a propensity to form a helix (residues Arg724−Ala735) and part (the NPLY motif) has a tendency to form a β-turn.
"In aqueous solution, the alphaIIb and beta3 tails are largely unstructured."
Protein: DP01842 (UniProt P05106)
Region: residues 763	to 788
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
However, its C-terminal A737–T762 is disordered, consistent with the secondary structure analysis.
Protein: DP01842 (UniProt P05106)
Region: residues 765	to 775
Annotation: protein binding (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
Here we report the crystal structure of the principal integrin binding and activating fragment of talin, alone and in complex with fragments of the beta 3 integrin tail.
Cross-references: PDB:1MK7
Protein: DP01842 (UniProt P05106)
Region: residues 762	to 788
Annotation: protein binding (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Here we present the detailed structural analysis of Shc phosphotyrosine-binding (PTB) domain in complex with the bi-phosphorylated β(3)integrin cytoplasmic tail (CT).
Cross-references: PDB:2L1C
Protein: DP01842 (UniProt P05106)
Region: residues 742	to 788
Annotation: protein binding (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Here, we report the structure of the cytoplasmic domain of human integrin αIIbβ3 bound to its inhibitor, the immunoglobin repeat 21 of filamin A (FLNa-Ig21).
Cross-references: PDB:2MTP
Protein: DP01842 (UniProt P05106)
Region: residues 783	to 787
Annotation: phosphorylation display site (Disorder function)
Evidence: immunodetection assay evidence used in manual assertion
Supporting statements:
In this paper we demonstrate that the beta 3 subunit of alpha IIb beta 3 was phosphorylated on tyrosine residues in response to thrombin-induced platelet aggregation.
Protein: DP01842 (UniProt P05106)
Region: residues 777	to 781
Annotation: phosphorylation display site (Disorder function)
Evidence: immunodetection assay evidence used in manual assertion
Supporting statements:
However, the presence of phosphate on this threonine inhibited the binding of Shc to tyrosyl-phosphorylated β3 peptide.
Protein: DP01842 (UniProt P05106)
Region: residues 771	to 775
Annotation: phosphorylation display site (Disorder function)
Evidence: immunodetection assay evidence used in manual assertion
Supporting statements:
Interestingly, alpha(nu)beta(3) was also found to directly interact with RPTPbeta/zeta, and PTN-induced Y773 phosphorylation of beta(3) integrin was dependent on both RPTPbeta/zeta and the downstream c-src kinase activation.
Protein: DP01842 (UniProt P05106)
Region: residues 780	to 783
Annotation: protein binding (Molecular function)
Evidence: fluorescence polarization evidence used in manual assertion
Supporting statements:
Furthermore, we validated that an LC3-interacting region (LIR) in integrin β3 bound to the ATG8 domains of the autophagy receptors MAP1LC3 and GABARAP in a manner enhanced by LIR-adjacent phosphorylation.
The integrin β3 tail contains a phospho-regulated LIR motif
Table 3 Affinities of ATG8 domains for the integrin β3 peptide.
KI values for ATG8 domains calculated from displacement experiments using unphosphorylated integrin β3 peptide and phosphorylated peptides (pThr777, pSer778, pThr779, pTyr785, or pThr779 pTyr785). Indicated error is the error of the mean (SEM); n = 3 replicates. N.B., no or low affinity (KI > 100 μM); N.M., not measured.
Table 4 Constructs used for expression of protein domains.
Protein domains and the encoding plasmids. Species is human unless otherwise stated.
The functional LIR motif FTNI in positions 780-783 is inside the disordered fragment region in positions 741-788.
Protein: DP01842 (UniProt P05106)
Region: residues 780	to 783
Annotation: selective autophagy (Biological process)
Evidence: fluorescence polarization evidence used in manual assertion
Supporting statements:
Furthermore, we validated that an LC3-interacting region (LIR) in integrin β3 bound to the ATG8 domains of the autophagy receptors MAP1LC3 and GABARAP in a manner enhanced by LIR-adjacent phosphorylation.
The integrin β3 tail contains a phospho-regulated LIR motif
Table 3 Affinities of ATG8 domains for the integrin β3 peptide.
KI values for ATG8 domains calculated from displacement experiments using unphosphorylated integrin β3 peptide and phosphorylated peptides (pThr777, pSer778, pThr779, pTyr785, or pThr779 pTyr785). Indicated error is the error of the mean (SEM); n = 3 replicates. N.B., no or low affinity (KI > 100 μM); N.M., not measured.
Table 4 Constructs used for expression of protein domains.
Protein domains and the encoding plasmids. Species is human unless otherwise stated.
The functional LIR motif FTNI in positions 780-783 is inside the disordered fragment region in positions 741-788.
Protein: DP01843 (UniProt P03404)
Region: residues 1	to 25
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
In dilute aqueous solution, the N terminus is unstructured, but in nonpolar, membrane-like environments, this helical structure is quite stable.
Protein: DP01844 (UniProt Q92540)
Region: residues 111	to 143
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
"a long, disordered loop between residues 111 to 143
Cross-references: PDB:1YA0
Protein: DP01845 (UniProt Q13451)
Region: residues 1	to 12
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The residues 1–12 upstream of helix 1 were disordered in the structures of FKBP51(1–140), consistent with the poor sequence conservation in this segment.
Cross-references: PDB:3O5E
Protein: DP01848 (UniProt P05107)
Region: residues 735	to 769
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Both of them are extended, but the peptide does not form a β-strand in the 14-3-3 complex as seen in the filamin complex. This indicates that the integrin cytoplasmic tail can adopt different conformations depending of its binding partner. In the crystal structures, we see only those parts of the cytoplasmic tail peptides that are in direct contacts, whereas the other regions apparently are disordered.
Cross-references: PDB:2jf1
Protein: DP01848 (UniProt P05107)
Region: residues 735	to 769
Annotation: disorder to order (Structural transition)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The β2 peptide bound to IgFLNa21 in a very similar way as the β7 peptide,3 forming a hydrogen-bonded β-strand next to the strand C of IgFLNa21 and interacting hydrophobically with the side chains of strand D (Figure 3C,D)
Protein: DP01848 (UniProt P05107)
Region: residues 735	to 769
Annotation: molecular function regulator (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
Our results suggest that the phosphorylation of beta2 integrins on Thr758 acts as a molecular switch to inhibit filamin binding and allow 14-3-3 protein binding to the integrin cytoplasmic domain, thereby modulating T-cell adhesion.
Protein: DP01848 (UniProt P05107)
Region: residues 756	to 760
Annotation: phosphorylation display site (Disorder function)
Evidence: qualitative western immunoblotting evidence used in manual assertion
Supporting statements:
Our results suggest that the phosphorylation of beta2 integrins on Thr758 acts as a molecular switch to inhibit filamin binding and allow 14-3-3 protein binding to the integrin cytoplasmic domain, thereby modulating T-cell adhesion.
Protein: DP01849 (UniProt O60260)
Region: residues 378	to 391
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The IBR-R2 linker region (which we refer to as the tether: residues 378–414) is 37 residues long. Most of the beginning of the tether (14 residues) is disordered, while the latter part runs across the surface of R1
Cross-references: PDB:4I1H
Protein: DP01849 (UniProt O60260)
Region: residues 378	to 391
Annotation: flexible linker (Disorder function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
The IBR-R2 linker region (which we refer to as the tether: residues 378–414) is 37 residues long. Most of the beginning of the tether (14 residues) is disordered, while the latter part runs across the surface of R1
Cross-references: PDB:4I1H
Protein: DP01849 (UniProt O60260)
Region: residues 73	to 99
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Residues before the ACT element (amino acids 73–99) and after the ACT element (amino acids 109–142) are disordered in our structure.
Cross-references: PDB:6GLC
Protein: DP01849 (UniProt O60260)
Region: residues 109	to 142
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Residues before the ACT element (amino acids 73–99) and after the ACT element (amino acids 109–142) are disordered in our structure.
Cross-references: PDB:6GLC