LiteFold/DisProt huggingface dataset:
Protein: DP03212 (UniProt P0DTC9)
Region: residues 370	to 419
Annotation: protein homodimerization activity (Molecular function)
Evidence: quantitative mass spectrometry evidence used in manual assertion
Supporting statements:
Removal of the Narm and Carm (NNTD-LKR-CTD) results in two major species that are similar to NWT. However, both NNTD-LKR-CTD populations display reduced polydispersity (narrower peak width, Figure S2A), suggesting that both Narm and Carm contribute to N oligomerization.
Protein: DP03212 (UniProt P0DTC9)
Region: residues 370	to 419
Annotation: RNA stem-loop binding (Molecular function)
Evidence: fluorescence anisotropy evidence used in manual assertion
Supporting statements:
Furthermore, the Narm and Carm may contribute more to slRNA binding than ssRNA because the impact on N binding is more pronounced after removal of the Narm or Carm (Figure S3C).
Protein: DP03212 (UniProt P0DTC9)
Region: residues 1	to 43
Annotation: RNA stem-loop binding (Molecular function)
Evidence: fluorescence anisotropy evidence used in manual assertion
Supporting statements:
Furthermore, the Narm and Carm may contribute more to slRNA binding than ssRNA because the impact on N binding is more pronounced after removal of the Narm or Carm (Figure S3C).
Protein: DP03212 (UniProt P0DTC9)
Region: residues 1	to 43
Annotation: RNA stem-loop binding (Molecular function)
Evidence: deletion mutation phenotypic evidence used in manual assertion
Supporting statements:
Truncation of the Narm results in an increase of the RNA-free peak (p3), suggesting that N truncations can alter the structure of N and correspondingly impact RNA binding and oligomerization. When both Narm and Carm were removed, we observed an even greater shift to p3, suggesting that both arms contribute to RNA-binding interactions.
Protein: DP03212 (UniProt P0DTC9)
Region: residues 370	to 419
Annotation: RNA stem-loop binding (Molecular function)
Evidence: deletion mutation phenotypic evidence used in manual assertion
Supporting statements:
Truncation of the Narm results in an increase of the RNA-free peak (p3), suggesting that N truncations can alter the structure of N and correspondingly impact RNA binding and oligomerization. When both Narm and Carm were removed, we observed an even greater shift to p3, suggesting that both arms contribute to RNA-binding interactions.
Protein: DP03212 (UniProt P0DTC9)
Region: residues 370	to 419
Annotation: molecular condensate scaffold activity (Molecular function)
Evidence: electron microscopy evidence used in manual assertion
Supporting statements:
To determine if N regions that impact RNA binding also impact liquid droplet formation, we next examined the role of Narm and Carm. NNTD-LKR-CTD-Carm behaves similarly to NWT, having loose coils in p1 (Figure 4B, middle left) and forming spherical liquid droplets in p2 (Figure 4B, middle right). However, examination of p2 from NNTD-LKR-CTD (Figure 4B, bottom right) revealed a much smaller population of liquid droplets (red arrow) and mostly crystal-like needle aggregates, suggesting that the Carm is important for droplet formation. A transition from spherical liquids to needle-like solids is consistent with the liquid-to-solid transitions observed for other proteins that undergo phase separation (Patel et al., 2015).
Protein: DP03212 (UniProt P0DTC9)
Region: residues 1	to 68
Annotation: poly(U) RNA binding (Molecular function)
Evidence: fluorescence resonance energy transfer evidence used in manual assertion
Supporting statements:
With increasing concentration of poly(rU), we observe a modulation of the transfer efficiency distribution with a shift toward lower transfer efficiencies, from a mean transfer efficiency E = 0.709 ± 0.009 in absence of RNA to E = 0.542 ± 0.003 in presence of 10 μM of poly(rU) (Figure 2). This observation clearly supports that the disordered tail is directly affected by the binding of RNA.
Based on these observations, the affinity of the NTD-RBD constructs appears to be ∼40–80 times tighter than that of the RBD alone, pointing to a direct contribution of the disordered region in favoring RNA binding.
Taken together with the tighter Kint observed for NTD-RBD, these observations indicate that the complex between RNA and NTD-RBD is not solely initiated by contacts with the RBD domain but instead relies on dynamic interactions between the RNA and both RBD and NTD.
Protein: DP03212 (UniProt P0DTC9)
Region: residues 1	to 68
Annotation: disorder (Structural state)
Evidence: fluorescence resonance energy transfer evidence used in manual assertion
Supporting statements:
ns-FCS measurements of the NTDL-RBD in the absence of RNA reveals a reconfiguration time of approximately 110 ± 20 ns, which is marginally affected upon binding RNA, with a reconfiguration time of the NTD spanning a range between 94 and 108 ns across the different lengths tested from (rU)10 to (rU)40 (Supplementary Figure S3). This indicates that the NTD remains largely dynamic and contacts must occur only across a small set of nucleotides.
Protein: DP03212 (UniProt P0DTC9)
Region: residues 1	to 68
Annotation: poly(U) RNA binding (Molecular function)
Evidence: mutant phenotype evidence used in manual assertion
Supporting statements:
These observations overall support that the mode of binding of RNA is similar between NTDL RBD (Wuhan-Hu-1) and OmNTDL-RBD (as supported by the same transfer efficiency in the bound state), but with different affinities (as indicated by the concentration dependence).
(C) Comparison of binding affinity for Wuhan-Hu-1 (red) and Omicron variant (cyan) reveals different affinities for poly(rU). Solid lines are fit to Equation (2).
Overall, our observations indicate that small changes in the sequence composition of NTD may not alter the overall conformational behavior of the chain, but can significantly impact the binding affinity.
Our results on the impact of the Omicron NTD mutations clearly show that alterations of three amino acids in this IDR are sufficient to decrease the interaction affinity between the construct and the nucleic acid. 
The authors assessed the poly(U) RNA binding capability of the NTD Omicron variant (that carries a proline to leucine substitution in position 13 and deletion of three residues between positions 31 and 33) and found it to be of lesser affinity that the wildtype/ Wuhan-Hu-1 type.
Protein: DP03212 (UniProt P0DTC9)
Region: residues 1	to 43
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Figure 1. - Panels A and B report the spectra obtained through the mr_CON//HN experiment. The 2D HN spectrum (A) shows a set of well-isolated signals deriving from the globular NTD domain as well as a number of signals, clustered in a narrow central region of the spectrum, deriving from the IDRs. The 2D CON spectrum (B) allows achieving the necessary resolution to investigate resonances from IDRs, including signals of proline residues. While IDR peaks fall in a very crowded region of the HN spectrum (1.1 ppm on 1H dimension), they are well dispersed in the CON spectrum (7.2 ppm on 13C dimension), as indicated by the two boxes. A zoom of a region of the two spectra centered at 120 ppm for 15N is reported in panels (C,D) to stress this concept.
Protein: DP03212 (UniProt P0DTC9)
Region: residues 181	to 248
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Figure 1. - Panels A and B report the spectra obtained through the mr_CON//HN experiment. The 2D HN spectrum (A) shows a set of well-isolated signals deriving from the globular NTD domain as well as a number of signals, clustered in a narrow central region of the spectrum, deriving from the IDRs. The 2D CON spectrum (B) allows achieving the necessary resolution to investigate resonances from IDRs, including signals of proline residues. While IDR peaks fall in a very crowded region of the HN spectrum (1.1 ppm on 1H dimension), they are well dispersed in the CON spectrum (7.2 ppm on 13C dimension), as indicated by the two boxes. A zoom of a region of the two spectra centered at 120 ppm for 15N is reported in panels (C,D) to stress this concept.
Protein: DP03212 (UniProt P0DTC9)
Region: residues 181	to 248
Annotation: RNA binding (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
NMR spectroscopy reveals at the residue level the importance of the two disordered regions for the interaction with RNA.
As an example, Figure 3 shows the enlargement of selected portions of the 2D CON in diagnostic spectral regions such as that of glycine (top) and proline residues (bottom). Addition of 0.1 equivalents of RNA shows intensity changes for specific cross-peaks, suggesting the presence of preferred IDR sites for the interaction with RNA.
Protein: DP03212 (UniProt P0DTC9)
Region: residues 181	to 248
Annotation: flexible linker (Disorder function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The results indicate that the NTR construct has a higher affinity towards RNA compared to the NTD alone as indicated by gel shifts observed at lower concentrations. While both NTD-containing proteins show binding to RNA, the two IDRs flanking the NTD visibly increase affinity to RNA.
Protein: DP03212 (UniProt P0DTC9)
Region: residues 1	to 43
Annotation: flexible N-terminal tail (Disorder function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The results indicate that the NTR construct has a higher affinity towards RNA compared to the NTD alone as indicated by gel shifts observed at lower concentrations. While both NTD-containing proteins show binding to RNA, the two IDRs flanking the NTD visibly increase affinity to RNA.
Protein: DP03212 (UniProt P0DTC9)
Region: residues 1	to 43
Annotation: RNA binding (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
NMR spectroscopy reveals at the residue level the importance of the two disordered regions for the interaction with RNA.
As an example, Figure 3 shows the enlargement of selected portions of the 2D CON in diagnostic spectral regions such as that of glycine (top) and proline residues (bottom). Addition of 0.1 equivalents of RNA shows intensity changes for specific cross-peaks, suggesting the presence of preferred IDR sites for the interaction with RNA.
Protein: DP03212 (UniProt P0DTC9)
Region: residues 1	to 43
Annotation: RNA binding (Molecular function)
Evidence: electrophoretic mobility shift assay evidence used in manual assertion
Supporting statements:
The results indicate that the NTR construct has a higher affinity towards RNA compared to the NTD alone as indicated by gel shifts observed at lower concentrations. While both NTD-containing proteins show binding to RNA, the two IDRs flanking the NTD visibly increase affinity to RNA.
Protein: DP03212 (UniProt P0DTC9)
Region: residues 181	to 248
Annotation: RNA binding (Molecular function)
Evidence: electrophoretic mobility shift assay evidence used in manual assertion
Supporting statements:
The results indicate that the NTR construct has a higher affinity towards RNA compared to the NTD alone as indicated by gel shifts observed at lower concentrations. While both NTD-containing proteins show binding to RNA, the two IDRs flanking the NTD visibly increase affinity to RNA.
Protein: DP03213 (UniProt P69411)
Region: residues 17	to 46
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
N-terminal Segment of RcsF Is Disordered
The protein that was used for crystallization was expressed as a soluble protein containing a C-terminal His tag and lacking the first 16 residues corresponding to the signal peptide and the lipobox (remember that RcsF is a lipoprotein whose lipid moiety is anchored in the outer membrane). However, the observed electron density begins at residue Pro48, suggesting that about 30 residues in the N-terminal part of the protein are completely disordered. The integrity of the sequence of the purified protein was confirmed using mass spectrometry to rule out any nonspecific proteolytic cleavage of the protein during expression and purification. The measured average mass was 13,609  2 Da, which is in good agreement with a theoretical average mass of 13,612 Da taking into account the complete processing of the N-terminal methionine.
Therefore, we decided to study the ability of a truncated version of the protein (RcsFtrunc), corresponding to residues Pro48 to Lys134, to induce the Rcs phosphorelay when expressed in the periplasm, using strain mucoidity as a read-out. As explained in the Introduction, induction of the Rcs system leads to colanic acid production, which results in a distinctive mucoid phenotype. As indicated in Table 2, we observed that expression of RcsFtrunc leads to a mucoid phenotype comparable with that observed when wild-type RcsF is expressed unanchored in the periplasm (supplemental Fig. S1). Thus, we can conclude from this experiment that the fraction of the polypeptide chain that is disordered in the crystal is not required for signaling, at least when RcsF is expressed as a soluble protein in the periplasm.
Cross-references: PDB:2Y1B
Protein: DP03214 (UniProt O60508)
Region: residues 1	to 82
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The N-terminal region of CDC40 is disordered, as referenced in Table S2 and confirmed upon visual inspection of the structure.
Cross-references: PDB:5XJC
Protein: DP03215 (UniProt Q9H875)
Region: residues 1	to 50
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The N-terminal region of PRKRIP1 is disordered, as referenced in Table S2 and confirmed upon visual inspection of the structure.
Cross-references: PDB:5XJC
Protein: DP03215 (UniProt Q9H875)
Region: residues 143	to 184
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The C-terminal region of PRKRIP1 is disordered, as referenced in Table S2 and confirmed upon visual inspection of the structure.
Cross-references: PDB:5XJC
Protein: DP03216 (UniProt Q96EQ8)
Region: residues 1	to 32
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The predicted unstructured N-terminal 30 amino acids were not observed in the electron density
Regions (1-32) updated based on missing residues in PDB files 
Cross-references: PDB:5DKA
Protein: DP03217 (UniProt Q9XWG3)
Region: residues 1	to 20
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Figure 3 The full-length Tdp2 has a modular architecture. (a) Fulllength
cTdp2 molecule in the crystal, with residue numbers indicated.
The N-terminal 20 residues as well as the linker between the α-helical
bundle and the catalytic domain are disordered (dotted lines).
Cross-references: PDB:4FVA
PDB:4GEW
PDB:4F1I
Protein: DP03217 (UniProt Q9XWG3)
Region: residues 98	to 111
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Despite a disordered linker between the a-helical bundle and the
catalytic domain (residues 98–111)
Figure 3 The full-length Tdp2 has a modular architecture. (a) Fulllength
cTdp2 molecule in the crystal, with residue numbers indicated.
The N-terminal 20 residues as well as the linker between the α-helical
bundle and the catalytic domain are disordered (dotted lines).
Cross-references: PDB:4FVA
PDB:4GEW
PDB:4F1I
Protein: DP03217 (UniProt Q9XWG3)
Region: residues 98	to 111
Annotation: flexible linker (Disorder function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
Despite a disordered linker between the a-helical bundle and the
catalytic domain (residues 98–111)
Figure 3 The full-length Tdp2 has a modular architecture. (a) Fulllength
cTdp2 molecule in the crystal, with residue numbers indicated.
The N-terminal 20 residues as well as the linker between the α-helical
bundle and the catalytic domain are disordered (dotted lines).
Cross-references: PDB:4FVA
PDB:4GEW
PDB:4F1I
Protein: DP03218 (UniProt O76463)
Region: residues 404	to 422
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Theexperimental map was of sufficient quality to build from residues 13 tothe carboxyl terminus of each non-identical, 440 amino acid polypeptidewith 23 residues missing from the Fhit domain of one molecule and 30residues  missing  from  the  other.
These 23 amino acids corresponds to the protein region comprised between residues 404 and 422, approximately, as indicated in PDB:1EMS and disorder predictors as MobiDB
Cross-references: PDB:1EMS
Protein: DP03219 (UniProt Q9U3N4)
Region: residues 370	to 389
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The Met1 to Gly6 residues at the
N-terminal end, Ile52 and Gly53 following TM1, and Glu370 to
the C-terminal end were not assigned due to the disorder of
the structure.
Approximately 20 residues at the C-terminal end are missing and
may possibly account for the cytoplasmic bobble found in
INX-6dN.
Dashed lines indicate unassigned residues due to disorder.
Dashed lines in figure 2 are located at the end of TM1, and at the C- and N-terminus end region.
Cross-references: PDB:5H1Q
PDB:5H1R
Protein: DP03219 (UniProt Q9U3N4)
Region: residues 252	to 261
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The antiparallel E2 beta sheets mostly disappeared, and the hairpin loop was disordered from R252 to D261
Cross-references: PDB:6KFG
PDB:6KFF
PDB:6KFH
Protein: DP03219 (UniProt Q9U3N4)
Region: residues 87	to 100
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The E1 outer lobe contained relaxed and disordered residues from D87 to V100, which
prevent the E1 outer lobe from interfacing with the opposed hemichannel
Cross-references: PDB:6KFG
PDB:6KFF
PDB:6KFH
Protein: DP03221 (UniProt P55265)
Region: residues 202	to 296
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Here we present the solution NMR backbone assignment of Zα-Zβ from H. Sapiens ADAR1. The predicted secondary structure of Zα-Zβ based on chemical shifts is in agreement with previously determined structures of Zα and Zβ in isolation, and indicates that the linker is intrinsically disordered. Comparison of the chemical shifts between the individual Zα and Zβ domains to the full Zα-Zβ construct suggests that Zβ may interact with the linker, the function of which is currently unknown.
First, the linker between the Zα and Zβ domains is intrinsically disordered, as determined by its low chemical shift dispersion and favorable relaxation properties (Fig. 2).
Protein: DP03221 (UniProt P55265)
Region: residues 202	to 296
Annotation: flexible linker (Disorder function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Here we present the solution NMR backbone assignment of Zα-Zβ from H. Sapiens ADAR1. The predicted secondary structure of Zα-Zβ based on chemical shifts is in agreement with previously determined structures of Zα and Zβ in isolation, and indicates that the linker is intrinsically disordered. Comparison of the chemical shifts between the individual Zα and Zβ domains to the full Zα-Zβ construct suggests that Zβ may interact with the linker, the function of which is currently unknown.
First, the linker between the Zα and Zβ domains is intrinsically disordered, as determined by its low chemical shift dispersion and favorable relaxation properties (Fig. 2).
Protein: DP03222 (UniProt Q92783)
Region: residues 140	to 170
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The {(1)H}-(15)N heteronuclear NOE experiments revealed that an unstructured and flexible loop region connects the VHS domain and UIM.
The amino acid sequences of STAM1N191 are shown in Fig. 1b. STAM1N191 consists of the VHS domain (M1-G139), the connecting region (V140-K170), and UIM (K171-S191). 1H-15N HSQC spectrum of STAM1N191 and the assigned residues are shown in Fig. 1b. Most of the resonances from the VHS domain were well dispersed, however, those from the connecting region and UIM showed narrow chemical shift dispersion and intense signals.
Protein: DP03222 (UniProt Q92783)
Region: residues 140	to 170
Annotation: flexible linker (Disorder function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The {(1)H}-(15)N heteronuclear NOE experiments revealed that an unstructured and flexible loop region connects the VHS domain and UIM.
The amino acid sequences of STAM1N191 are shown in Fig. 1b. STAM1N191 consists of the VHS domain (M1-G139), the connecting region (V140-K170), and UIM (K171-S191). 1H-15N HSQC spectrum of STAM1N191 and the assigned residues are shown in Fig. 1b. Most of the resonances from the VHS domain were well dispersed, however, those from the connecting region and UIM showed narrow chemical shift dispersion and intense signals.
Protein: DP03223 (UniProt P33316-2)
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:
Lower thermostability may be partially due to increased flexibility of N- and C-terminal segments. In fact, the N-terminus could not be localized in the 3D structure, and for one monomer, the C-terminus was also missing from the density maps.
Cross-references: PDB:2HQU
Protein: DP03224 (UniProt Q97W73)
Region: residues 119	to 148
Annotation: disorder (Structural state)
Evidence: cleavage assay evidence used in manual assertion
Supporting statements:
Sulfolobus SSB lacks the zinc finger motif found in the eucaryal and euryarchaeal proteins, possessing instead a flexible C-terminal tail, sensitive to trypsin digestion, that is not required for DNA binding.
This allowed the unambiguous identification of the site of cleavage by trypsin as Arg-119, the first arginine present in the Gly/Pro-rich C-terminal region, suggesting that the C-terminal 30 amino acids of Sulfolobus SSB exist in a flexible conformation.
Protein: DP03225 (UniProt P19957)
Region: residues 23	to 60
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Figure 1b shows the assigned 1H-15N HSQC spectra of the 15N, 13C labelled trappin-2. As expected, the dispersion of the resonances shows that the elafin domain (A39-Q95) is well folded whereas the cementoin domain (A1-K38) shows a narrow profile with chemical shift values close to random coil values which is typical for an intrinsically disordered domain.
Our results strongly suggest that the cementoin domain is disordered in the context of the full length protein (not just as the isolated form) under our experimental conditions.