LiteFold/DisProt huggingface dataset:
Protein: DP02921 (UniProt P26368)
Region: residues 231	to 258
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Previous studies on the RNA binding of U2AF2mostly focused on RRM1 and RRM2, but suggested a potential role of the intervening linker region (residues 231 to 258) for regulating the dynamic RNA recognition by U2AF2
The RRM1–RRM2 linker is flexible, as indicated by low heteronuclear NOE values. The highest flexibility is ob-served for the N-terminal region of the linker (residues 235 to249), beyond the residues (D231/Y232) that stabilize helixα0.Consistently, NMR signals corresponding to these N-terminal linker residues (residues 235 to 245) in NMR spectra of the constructs, RRM1–linker and linker–RRM2, superimpose well with those in the spectrum of RRM1,2, indicative of their intrinsically disordered nature and absence of contacts to RRM1or RRM2
Protein: DP02921 (UniProt P26368)
Region: residues 250	to 259
Annotation: protein binding (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Indeed, our experimental heteronuclear NOEvalues display a gradual increase in the C-terminal region of the linker (residues 250 to 258) toward the RRM2 domain, indicative of limited flexibility (Fig. 1C). This is consistent with the interaction of the C-terminal region of the RRM1–RRM2 linker with the RNA binding interface of RRM2, as seen in our structure (Fig. 1B), although in a dynamic manner.
 the C-terminal region of the linker (residues 250 to 259) adopts a well-defined conformation in the solution structure and binds to RRM2, supported by 84 distance restraints derived from proton–proton nuclear Overhauser enhancements (NOEs) between the linker and RRM2. In detail, three residues (V250/S251/T252) are packed against to the N-terminal end of strandβ2 in RRM2 (K286/A288/F288) in an antiparallel manner, while the rest of this region (residues 253 to259) interacts with residues in the RRM2β-sheet.
Cross-references: PDB:6TR0
Protein: DP02921 (UniProt P26368)
Region: residues 231	to 235
Annotation: protein binding (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
First, two additional short helices form at the N terminus of RRM1, helixα0, and at the C terminus of RRM2, helixαC (Fig. 1B). In particular, the orientation of the N-terminal helix is stabilized by interactions with residues at the N-terminal region of the RRM1–RRM2 linker(D231/Y232)
Protein: DP02921 (UniProt P26368)
Region: residues 231	to 258
Annotation: molecular function inhibitor activity (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The Linker Plays an Autoinhibitory Role in Py-Tract RNA Binding.The interaction with the RNA binding interface of RRM2 suggests a potential role of the RRM1–RRM2 linker in regulating RNA binding. To further explore this, we removed the linker/RRM2contacts by replacing the core linker region (residues 233 to 257)with Gly-Gly-Ser repeats of the same length
RRM1,2-GS comprises two functional RRM domains butlacks the contacts of the RRM1,2 linker to RRM2.
the competition of linker and RNA for RRM2favors binding of strong over weak Py-tracts.
These data further corroborate the autoinhibitory role of the linker, and show that the dynamic linker/RRM2 interaction reduces the RNA binding affinity of RRM1,2. The linker thereby proofreads against the binding of weak RNA ligands by directly competing for the RNA binding interface on the RRM2. Of note, the autoinhibitory role of the linker is also recapitulated in the context of the minimal U2AFheterodimer (SI Appendix,Fig.S6B), indicating that the presence of the small subunit U2AF1 does not affect or modulate theRRM2/linker interaction.
Protein: DP02921 (UniProt P26368)
Region: residues 231	to 258
Annotation: flexible linker (Disorder function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Previous studies on the RNA binding of U2AF2mostly focused on RRM1 and RRM2, but suggested a potential role of the intervening linker region (residues 231 to 258) for regulating the dynamic RNA recognition by U2AF2
The RRM1–RRM2 linker is flexible, as indicated by low heteronuclear NOE values. The highest flexibility is ob-served for the N-terminal region of the linker (residues 235 to249), beyond the residues (D231/Y232) that stabilize helixα0. Consistently, NMR signals corresponding to these N-terminal linker residues (residues 235 to 245) in NMR spectra of the constructs, RRM1–linker and linker–RRM2, superimpose well with those in the spectrum of RRM1,2, indicative of their intrinsically disordered nature and absence of contacts to RRM1or RRM2
Cross-references: PDB:6TR0
Protein: DP02922 (UniProt P01215)
Region: residues 33	to 57
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The solution structure of dg-alpha hCG is represented by an ensemble of 27 structures. In comparison to the crystal structure of the dimer, the solution structure of free dg-alpha hCG exhibits: (a) an increased structural disorder (residues 33-57); (b) a different backbone conformation near Val76 and Glu77; and (c) a larger flexibility.
The disorder present in the segment comprising residues 33–57 reflects the absence of medium‐and long‐range NOEs. This is in good agreement with the random coil 1H chemical shifts of the corresponding residues
The two hairpins are connected by a disordered loop consisting of the residues 33–57.
From Fig. 6 it is obvious that free dg‐αhCG is a rather flexible molecule. This is reflected by the disorder we observed for the loop comprising residues α33–57, and also by the conformational heterogeneity of the hairpin loop α70–74 and the tight turn α20–23. 
Cross-references: PDB:1DZ7
Protein: DP02922 (UniProt P01215)
Region: residues 1	to 10
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The N‐ and C‐terminal segments, comprising residues 1–10 and 85–92, respectively, are also disordered and stick out into the solution like two arms.
Cross-references: PDB:1DZ7
Protein: DP02923 (UniProt P33128)
Region: residues 122	to 132
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The residues 42-49, 98-108, 146, and 147 of the protein were not observed in the electron density map, which appears to be highly flexible.
The highly flexible region 98-108 corresponds to region 122-132 on the protein sequence, since region 1-25 of the protein was excluded from the crystal structure as it corresponds to a signal peptide.
Cross-references: PDB:5ghu
Protein: DP02923 (UniProt P33128)
Region: residues 122	to 132
Annotation: flexible linker (Disorder function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
The residues 42-49, 98-108, 146, and 147 of the protein were not observed in the electron density map, which appears to be highly flexible.
The  polypeptide  chain  may  be  divided  into  two  major domains, the N-terminal domain (residues, 1-123) has immunoglobulin (Ig) like fold whereas the C-terminal  domain  has  β-barrel  fold  (residues,  130-222).
The highly flexible region 98-108 corresponds to region 122-132 on the protein sequence, since region 1-25 of the protein was excluded from the crystal structure as it corresponds to a signal peptide.
Cross-references: PDB:5ghu
Protein: DP02924 (UniProt P0C6X7)
Region: residues 1	to 12
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
We further characterized the full-length 179-residue protein and show that the polypeptide segments of residues 1 to 12 and 129 to 179 are flexibly disordered.
However, the presence of flexibly disordered regions in the protein identified by 1H NMR spectroscopy (see “Characterization of the full-length SARS-CoV nsp1” below) was consistent with the results of secondary structure prediction, which indicated that a few residues at the N terminus, as well as a greater number of residues in the C-terminal one-third of the protein, would not adopt regular secondary structure.
The structure of intact nsp1 includes a globular domain of residues 13 to 121 and the disordered regions of residues 1 to 12 and 122 to 179 (Fig. 1b).
Most of the resonances in full-length nsp1 that are not present in nsp1(13-128) have either small positive or negative 15N{1H} NOEs (Fig. 5c), showing that the polypeptide segments of residues 1 to 12 and 129 to 179 are best described as a short N-terminal and a long C-terminal flexibly disordered tail, respectively (Fig. ​1b).
Protein: DP02924 (UniProt P0C6X7)
Region: residues 129	to 179
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
We further characterized the full-length 179-residue protein and show that the polypeptide segments of residues 1 to 12 and 129 to 179 are flexibly disordered.
However, the presence of flexibly disordered regions in the protein identified by 1H NMR spectroscopy (see “Characterization of the full-length SARS-CoV nsp1” below) was consistent with the results of secondary structure prediction, which indicated that a few residues at the N terminus, as well as a greater number of residues in the C-terminal one-third of the protein, would not adopt regular secondary structure.
The structure of intact nsp1 includes a globular domain of residues 13 to 121 and the disordered regions of residues 1 to 12 and 122 to 179 (Fig. 1b).
Most of the resonances in full-length nsp1 that are not present in nsp1(13-128) have either small positive or negative 15N{1H} NOEs (Fig. 5c), showing that the polypeptide segments of residues 1 to 12 and 129 to 179 are best described as a short N-terminal and a long C-terminal flexibly disordered tail, respectively (Fig. ​1b).
Protein: DP02924 (UniProt P0C6X7)
Region: residues 75	to 87
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Increased flexibility of the polypeptide chain that causes reduced NOE intensities is found in the disordered loop between residues 75 and 87 and in the region of residues 94 to 103, which forms nonregular secondary structure with one γ-turn of residues 97 to 99 and a type II β-turn of residues 98 to 101 ​(Fig.1). 
Cross-references: BMRB:7014
PDB:2GDT
PDB:2HSX
Protein: DP02925 (UniProt P0DTD1)
Region: residues 1782	to 1796
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Unstructured region belonging to the Papain-like proteinase (PL-PRO)
Cross-references: PDB:6YVA
Protein: DP02925 (UniProt P0DTD1)
Region: residues 4254	to 4270
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
In addition, the α1′-helix of nsp10 was completely density-untraceable in our structure, which can be clearly observed in both SARS-CoV and MERS-CoV nsp10 (Fig. ​(Fig.1b1b).
Unstructured region belonging to the RNA-directed RNA polymerase (Pol/RdRp)
Cross-references: PDB:7C2J
PDB:7C2I
Protein: DP02925 (UniProt P0DTD1)
Region: residues 3931	to 3942
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The defined region relies on examining the missing coordinates in both reported cryo-EM structures attached to the publication (7btf and 6m71) and it belongs to Non-structural protein 7 (nsp7).
Cross-references: PDB:6M71
PDB:7BTF
Protein: DP02925 (UniProt P0DTD1)
Region: residues 3932	to 3942
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The defined region relies on examining the missing coordinates in both reported cryo-EM structures attached to the publication (7c2k and 7bzf) and it belongs to Non-structural protein 7 (nsp7).
Cross-references: PDB:7C2K
PDB:7BZF
Protein: DP02925 (UniProt P0DTD1)
Region: residues 3943	to 4020
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The defined region relies on examining the missing coordinates in the reported cryo-EM structure of the RNA-dependent RNA polymerase post-translocated catalytic complex - attached to the publication - and it belongs to Non-structural protein 8 (nsp8).
Cross-references: PDB:7BZF
Protein: DP02925 (UniProt P0DTD1)
Region: residues 3995	to 4020
Annotation: order to disorder (Structural transition)
Evidence: cryogenic electron microscopy evidence used in manual assertion
Supporting statements:
The defined region relies on examining the missing coordinates in both reported cryo-EM structures of the RNA-dependent RNA polymerase of the pre-translocated and post-translocated catalytic complex - attached to the publication - and it belongs to Non-structural protein 8 (nsp8).
Cross-references: PDB:7BZF
PDB:7C2K
Protein: DP02925 (UniProt P0DTD1)
Region: residues 3932	to 3942
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The defined region relies on examining the missing coordinates in the reported cryo-EM structure of replicating SARS-CoV-2 polymerase - attached to the publication - and it belongs to Non-structural protein 7 (nsp7).
Cross-references: PDB:6YYT
Protein: DP02925 (UniProt P0DTD1)
Region: residues 3982	to 4007
Annotation: RNA binding (Molecular function)
Evidence: cryogenic electron microscopy evidence used in manual assertion
Supporting statements:
The protruding, exiting RNA duplex is flanked by long α-helical extensions that are formed by the highly conserved17 N-terminal regions in the two nsp8 subunits (Figs. 2, 3). These prominent nsp8 extensions reach up to 28 base pairs away from the active site and use positively charged residues that are positioned to interact with the RNA backbones (Fig. 3).
The two nsp8 extensions differ with respect to their RNA interactions, which also argues for sequence-independent binding. The two nsp8 copies adopt different structures in the RdRp complex, and interact differently with nsp7 and nsp12 subdomains (Extended Data Fig. 3c). The nsp8 extensions also adopt different structures in crystals of nsp8–nsp7 complexes17,18, and are mobile in free RdRp15,16. This indicates that the nsp8 extensions are flexible in the RdRp complex and become ordered when an RNA duplex exits the enzyme.
The defined binding region mainly composed by positively charged residues relies on examining the reported cryo-EM structure attached to the publication along with Figure 3. 
Cross-references: PDB:6YYT
Protein: DP02925 (UniProt P0DTD1)
Region: residues 3948	to 4020
Annotation: disorder to order (Structural transition)
Evidence: cryogenic electron microscopy evidence used in manual assertion
Supporting statements:
The protruding, exiting RNA duplex is flanked by long α-helical extensions that are formed by the highly conserved17 N-terminal regions in the two nsp8 subunits (Figs. 2, 3). These prominent nsp8 extensions reach up to 28 base pairs away from the active site and use positively charged residues that are positioned to interact with the RNA backbones (Fig. 3).
The two nsp8 extensions differ with respect to their RNA interactions, which also argues for sequence-independent binding. The two nsp8 copies adopt different structures in the RdRp complex, and interact differently with nsp7 and nsp12 subdomains (Extended Data Fig. 3c). The nsp8 extensions also adopt different structures in crystals of nsp8–nsp7 complexes17,18, and are mobile in free RdRp15,16. This indicates that the nsp8 extensions are flexible in the RdRp complex and become ordered when an RNA duplex exits the enzyme.
Cross-references: PDB:6YYT
Protein: DP02925 (UniProt P0DTD1)
Region: residues 1	to 147
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
This may correspond to the flexibly disposed N-terminal domain of Nsp1 considering the 20-amino acid unstructured linker between the N- and C-terminal domains (Fig. 2e and Supplementary Fig. 1).
The C-terminal domain of Nsp1 binds to the mRNA entry site of 40S (red), while the N-terminal domain (gray) is flexibly disposed.
These results also agree with our structural findings that the C-terminal domain of Nsp1 is responsible for specific contacts with the ribosome, whereas the N-terminal domain is flexibly disposed.
Cross-references: PDB:6ZOK
PDB:6ZOJ
Protein: DP02925 (UniProt P0DTD1)
Region: residues 129	to 147
Annotation: flexible linker (Disorder function)
Evidence: cryogenic electron microscopy evidence used in manual assertion
Supporting statements:
This may correspond to the flexibly disposed N-terminal domain of Nsp1 considering the 20-amino acid unstructured linker between the N- and C-terminal domains (Fig. 2e and Supplementary Fig. 1).
Region 129-147 correspond to the flexible linker connecting the unstructured N-terminal domain of Nsp1 and its C-terminal domain, as also shown in Fig. 2e. 
Cross-references: PDB:6ZOK
PDB:6ZOJ
Protein: DP02925 (UniProt P0DTD1)
Region: residues 4254	to 4271
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The defined region relies on examining the missing coordinates in both reported X-ray structures attached to the publication (7C2J and 7C2I) and it is also missing in other unpublished structures of the Non-structural protein 10 (nsp10).
Cross-references: PDB:7C2J
PDB:7C2I
Protein: DP02925 (UniProt P0DTD1)
Region: residues 3837	to 3846
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The region is disordered based upon Fig.2.
Cross-references: BMRB:50337
Protein: DP02925 (UniProt P0DTD1)
Region: residues 3660	to 3681
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
Circular dichroism spectroscopy was used to monitor the conformational dynamics of NSP6 (91–112). In physiological pH buffer conditions, the peptide showed strong negative ellipticity at 198 nm, characteristic of random coil conformations (Fig. 4A).
Protein: DP02925 (UniProt P0DTD1)
Region: residues 3660	to 3681
Annotation: disorder to order (Structural transition)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
Interestingly, in the presence of organic solvent (TFE) and SDS, peptide showed negative ellipticity at 208 nm and 222 nm, which showed a gain in the helical conformation of peptide (Fig. 4B & C). The results showed that the surrounding environment has a strong role in conformational dynamics of NSP6 91–112 region. Organic solvent and SDS are well-acknowledged for their hydrophobic and biological membrane mimic properties, respectively
to see the impact of membrane-mediated environment on the NSP6 91–112 region, we have used DOPS liposome. The NSP6 91–112 region acquires partial helical conformation in the presence of DOPS (Fig. 4D).
Protein: DP02925 (UniProt P0DTD1)
Region: residues 3660	to 3681
Annotation: disorder to order (Structural transition)
Evidence: fluorescence evidence used in manual assertion
Supporting statements:
we have used the intrinsic tryptophan present in this peptide as a fluorescence probe to monitor the tertiary structure changes in the presence of SDS and TFE (Fig. 4E & F). Trp in the presence of non-polar/hydrophobic environment gives rise to a significant blue shift [33]. Furthermore, we have observed that in the presence of TFE and SDS peptide showed blue shift, which again confirms the tertiary structural changes are happening to the peptide in these conditions and following the results obtained from the CD spectroscopy.
In the presence of SDS (E) and TFE (F) peptide showed significant blue shift under the influence of hydrophobic environment.
Protein: DP02925 (UniProt P0DTD1)
Region: residues 3660	to 3681
Annotation: lipid binding (Molecular function)
Evidence: fluorescence evidence used in manual assertion
Supporting statements:
we have used the intrinsic tryptophan present in this peptide as a fluorescence probe to monitor the tertiary structure changes in the presence of SDS and TFE (Fig. 4E & F). Trp in the presence of non-polar/hydrophobic environment gives rise to a significant blue shift [33]. Furthermore, we have observed that in the presence of TFE and SDS peptide showed blue shift, which again confirms the tertiary structural changes are happening to the peptide in these conditions and following the results obtained from the CD spectroscopy.
In the presence of SDS (E) and TFE (F) peptide showed significant blue shift under the influence of hydrophobic environment.
Protein: DP02925 (UniProt P0DTD1)
Region: residues 3660	to 3681
Annotation: lipid binding (Molecular function)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
Interestingly, in the presence of organic solvent (TFE) and SDS, peptide showed negative ellipticity at 208 nm and 222 nm, which showed a gain in the helical conformation of peptide (Fig. 4B & C). The results showed that the surrounding environment has a strong role in conformational dynamics of NSP6 91–112 region. Organic solvent and SDS are well-acknowledged for their hydrophobic and biological membrane mimic properties, respectively
to see the impact of membrane-mediated environment on the NSP6 91–112 region, we have used DOPS liposome. The NSP6 91–112 region acquires partial helical conformation in the presence of DOPS (Fig. 4D).
Protein: DP02925 (UniProt P0DTD1)
Region: residues 148	to 180
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
The far-UV circular dichroism (CD) spectrum of Nsp1-CT features a negative ellipticity minimum at 200 nm and a negative ellipticity shoulder near 230 nm (Figure S1). The molar ellipticity minimum at 200 nm is about 40% of that expected for a random coil, suggesting an offsetting positive contribution from β-sheet or turn structures. (23) Decomposition of the spectrum into three components (α-helix, β-sheet, and random coil) indicates that the peptide adopts a dominant random coil configuration with an admixture of β-sheet and minimal (<5%) α-helix.
Protein: DP02925 (UniProt P0DTD1)
Region: residues 148	to 180
Annotation: disorder (Structural state)
Evidence: fluorescence resonance energy transfer evidence used in manual assertion
Supporting statements:
Employing laser spectroscopy, including time-resolved fluorescence energy transfer (TR-FRET), we have obtained nanosecond snapshots of rapidly fluctuating conformations in the Nsp1 C-terminal peptide (Nsp1-CT).