LiteFold/DisProt huggingface dataset:
Protein: DP02832 (UniProt Q7L2J0)
Region: residues 665	to 676
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
In the absence of RNA, the N-terminus (residues 418–431) and C-terminal β6-β7 loop (residues 665–676) are partially disordered (Fig. 2c,f), while in the presence of meSL1p, a helix α0 forms near the N-terminus, loop residues that connect to α1 become ordered, and the β6-β7 loop adopts an ordered structure with a short helix α7 in the middle.
Based on studies indicating that MePCE binds the proximal end of the 7SK SL1 and adjacent ssRNA in vivo (Fig. 1c), we designed and synthesized an RNA hairpin-ssRNA construct comprising the 5′-end of 7SK SL1 with a UUCG tetraloop and an eight nucleotide ssRNA 3′ overhang (SL1p).
The structures of MePCE–SAH in the absence and presence of SL1p are globally similar (all atom RMSD 0.29 Å), but there are major differences around the active site and RNA-protein interface (Fig. 2e,f). In the absence of RNA, the N-terminus (residues 418–431) and C-terminal β6-β7 loop (residues 665–676) are partially disordered (Fig. 2c,f), while in the presence of meSL1p, a helix α0 forms near the N-terminus, loop residues that connect to α1 become ordered, and the β6-β7 loop adopts an ordered structure with a short helix α7 in the middle (Fig. 2b,e).
Authors of the publication compare their crystal structures of MePCE-MT bound to SL1p (PDB: 6dcb, 6dcc) to an unpublished structure of unbound MePCE-MT (PDB:5UNA), to highlights the conformational changes in MePCEMT that occur on RNA binding.
Protein: DP02833 (UniProt Q9Y4F1)
Region: residues 862	to 909
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
They also have a second PH domain (referred to as PH2), which is connected to the first PH domain (PH1) by a ~70-residue linker.
Cross-references: PDB:4H6Y
Protein: DP02833 (UniProt Q9Y4F1)
Region: residues 862	to 909
Annotation: flexible linker (Disorder function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
They also have a second PH domain (referred to as PH2), which is connected to the first PH domain (PH1) by a ~70-residue linker.
Protein: DP02834 (UniProt Q9Y2Z0)
Region: residues 262	to 276
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The line-widths of the peaks in the spectrum of intact Sgt1 are smaller than expected for a single domain molecule over 30 kDa, strongly implying that the linkers between the domains are flexible and that any contacts between domains are not long-lived. Hence, the domains probably function in a coordinated but not necessarily cooperative manner.
Protein: DP02834 (UniProt Q9Y2Z0)
Region: residues 262	to 276
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Missing residues in the crystal structure of human Sgt1 corresponds to the region connecting CS domain and SGS domain.
Cross-references: PDB:1RL1
Protein: DP02834 (UniProt Q9Y2Z0)
Region: residues 262	to 276
Annotation: flexible linker (Disorder function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
Missing residues in the crystal structure of human Sgt1 corresponds to the region connecting CS domain and SGS domain.
Cross-references: PDB:1RL1
Protein: DP02834 (UniProt Q9Y2Z0)
Region: residues 262	to 276
Annotation: flexible linker (Disorder function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The line-widths of the peaks in the spectrum of intact Sgt1 are smaller than expected for a single domain molecule over 30 kDa, strongly implying that the linkers between the domains are flexible and that any contacts between domains are not long-lived. Hence, the domains probably function in a coordinated but not necessarily cooperative manner.
Cross-references: PDB:1RL1
Protein: DP02835 (UniProt Q14849)
Region: residues 216	to 230
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The final structural model includes residues 231–444 of StARD3 (the coordinates for residues 216–230 were omitted because no electron density was observed), 224 water molecules, three molecules of ethylene glycol, one sulfate ion and one molecule of l-(+)-tartaric acid.
Cross-references: PDB:5I9J
Protein: DP02835 (UniProt Q14849)
Region: residues 216	to 230
Annotation: flexible linker (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The final structural model includes residues 231–444 of StARD3 (the coordinates for residues 216–230 were omitted because no electron density was observed), 224 water molecules, three molecules of ethylene glycol, one sulfate ion and one molecule of l-(+)-tartaric acid.
Missing residues in the crystal structure corresponds to the IDR connecting the MENTAL domain to the SMART domain.
Protein: DP02836 (UniProt P24785)
Region: residues 81	to 164
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Only individual dsRBDs, consisting of residues 1–80 of dsRBD1 (Figure ​2B) and residues 165–247 of dsRBD2 (Figure ​2C), were visible in the electron density map. The linker region connecting the two domains is not visible, which is consistent with the hypothesis that this linker is normally disordered (Figure ​2A).
Cross-references: PDB:5ZTM
Protein: DP02836 (UniProt P24785)
Region: residues 81	to 164
Annotation: flexible linker (Disorder function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
Only individual dsRBDs, consisting of residues 1–80 of dsRBD1 (Figure ​2B) and residues 165–247 of dsRBD2 (Figure ​2C), were visible in the electron density map. The linker region connecting the two domains is not visible, which is consistent with the hypothesis that this linker is normally disordered (Figure ​2A).
Cross-references: PDB:5ZTM
Protein: DP02836 (UniProt P24785)
Region: residues 1	to 142
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
For each copy, well-defined electron density is present for residues 143–1158 of MLE (with the exception of a loop 311–321), as well as for ADP-AlF4, a magnesium ion, and 10 ribonucleotides (Table 1).
Cross-references: PDB:5AOR
Protein: DP02836 (UniProt P24785)
Region: residues 311	to 321
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
For each copy, well-defined electron density is present for residues 143–1158 of MLE (with the exception of a loop 311–321), as well as for ADP-AlF4, a magnesium ion, and 10 ribonucleotides (Table 1).
Cross-references: PDB:5AOR
Protein: DP02836 (UniProt P24785)
Region: residues 1159	to 1293
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
For each copy, well-defined electron density is present for residues 143–1158 of MLE (with the exception of a loop 311–321), as well as for ADP-AlF4, a magnesium ion, and 10 ribonucleotides (Table 1).
Cross-references: PDB:5AOR
Protein: DP02836 (UniProt P24785)
Region: residues 1	to 104
Annotation: disorder (Structural state)
Evidence: cleavage assay evidence used in manual assertion
Supporting statements:
Proteolysis of MLEΔC resulted in a stable 120 kDa fragment lacking dsRBD1 but containing dsRBD2 (MLE105-1158, referred to as MLEcore) (Figure S1A).
Cross-references: PDB:5AOR
Protein: DP02837 (UniProt Q9QXN5)
Region: residues 1	to 28
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
No electron density was found for the N-terminal residues 1–28. An N-terminal 3-kDa fragment is readily lost by proteolysis (15), but SDS/PAGE analysis of dissolved crystals (23) showed that the molecule was intact; these residues are assumed to be disordered in the crystal structure. The putative NADPH-binding motif identified by Yang et al. (19) is in this disordered region; we find no evidence of NADPH binding (data not shown). 
Cross-references: PDB:2HUO
Protein: DP02838 (UniProt P20807)
Region: residues 269	to 320
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Following the clear continuing electron density from the N terminus of IS1 (Asp268), eight residues were manually built in molecule B, and seven residues in molecules C and D, but only three residues could be traced in molecule A due to insignificant electron density thereafter. The C-terminal end of IS1 is missing, and electron density is not traceable until partway into PC2 at Pro319 in molecule B, Val320 in molecule C, Gln321 in molecule D, and Glu323 in molecule A. The missing portion of IS1 lies between the 1b and 2b autolysis sites (25, 26).
The limits of the disordered segment vary slightly in each structure, and are determined to be 269-320
Cross-references: PDB:6BJD
PDB:6BGP
PDB:6BDT
Protein: DP02838 (UniProt P20807)
Region: residues 269	to 320
Annotation: disorder (Structural state)
Evidence: cleavage assay evidence used in manual assertion
Supporting statements:
Both methods showed only 26- and 13-kDa species present. The former matched in size the ΔNS core up to the 1b IS1 cleavage site in PC2, and the latter matched the remainder of PC2 from the 2b IS1 cleavage site onward. These results from the C129S crystals are in agreement with a previous experiment using the Cys129 protease core (25) over a much shorter time frame. It suggests that IS1 of the C129S crystals was indeed autoproteolyzed during crystallization [...] Although there was no autolysis of C129A, most of IS1 still could not be built due to poor quality or missing electron density.

Cross-references: PDB:6BJD
PDB:6BGP
PDB:6BDT
Protein: DP02838 (UniProt P20807)
Region: residues 269	to 320
Annotation: disorder (Structural state)
Evidence: small-angle X-ray scattering evidence used in manual assertion
Supporting statements:
Small-angle X-ray scattering (SAXS) analysis of the C129A mutant suggested that IS1 is disordered and mobile enough to occupy several locations.
Therefore, the missing IS1 region was built in using the ensemble optimization method (EOM) (33). A large conformational pool (10,000 possibilities) was generated using sequence information and the crystal structure of Ca2+-bound calpain-3 C129S core as a template but with PC1 and PC2 unfixed and, therefore, free to rotate. However, only those conformers that were consistent with the SAXS experimental scattering data were retained. The final ensemble of conformers of the calpain-3 core with the IS1 structural model inserted was in excellent agreement with both sets of experimental scattering data,
Cross-references: PDB:6BJD
PDB:6BGP
PDB:6BDT
Protein: DP02838 (UniProt P20807)
Region: residues 269	to 320
Annotation: self-inhibition (Disorder function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
IS1, interrupts the protease core and must be cleaved for activation and substrate binding
the first cleavage as an essential step to activation through removal of an internal propeptide that otherwise blocks substrate access to the catalytic cleft (25).
But in addition to the metal ion requirement, it is known that calpain-3 has an additional inhibitory feature, which is IS1 acting as an internal autoinhibitory propeptide to block the enzyme's active site (25). Although in the Ca2+-bound crystal structure, most of IS1 is not visible, what can be seen of IS1 in the active site cleft supports the autoinhibition role. First, the N-terminal segment of IS1 (Met272-Thr273-Tyr274-Gly275) protrudes into the active-site cleft through the S3, S2, S1, and S1′ subsites and makes extensive contacts with residues on either side of the catalytic cleft (Fig. 8). (See detailed description below). Second, residues Val320-Gln321-Tyr322 located just beyond the C terminus of IS1 are part of PC2 that lies on the top of the active site, in which Val320 forms an interaction with residue Glu125 OE2 of PC1 (2.9 Å). Furthermore, an extended hydrophobic patch is formed
This region of IS1 that occupies the active-site cleft is perfectly conserved in the comparison of the IS1 sequences from 22 different mammals, which reinforces its functional importance (Fig. S3)
The flexible region occludes the active site, preventing rearrangements necessary for catalytic activity. It needs to undergo auto proteolysis to allow enzyme activation
Cross-references: PDB:6BJD
PDB:6BGP
PDB:6BDT
Protein: DP02839 (UniProt O43070)
Region: residues 330	to 553
Annotation: disorder (Structural state)
Evidence: cleavage assay evidence used in manual assertion
Supporting statements:
Nbs1 cardinal features: fused, extended, FHA-BRCT(1)-BRCT(2) domains flexibly linked to C-terminal Mre11- and ATM-binding motifs. 
To define functional Nbs1 regions, we expressed a series of truncated S. pombe Nbs1 (spNbs1) proteins and mapped structured domains with proteolysis
Trypsin degradation of Nbs1-ΔAT reveals a stable 37kDa folded core (Nbs1-fc, residues 1-329) encompassing the Nbs1 FHA domain and its two BRCT domains (Figures 1A and 1B). N-terminal sequencing of smaller transiently stable trypsin products maps three additional cleavage sites to a divergent sequence linking BRCT2 and the MB motif. Thus, the N-terminal 55% of spNbs1 comprises a composite FHA-BRCT1-BRCT2 folded Nbs1-fc that is linked to the C-terminal Mre11 and ATM binding regions via a protease-sensitive linker peptide.
Protein: DP02839 (UniProt O43070)
Region: residues 330	to 553
Annotation: disorder (Structural state)
Evidence: small-angle X-ray scattering evidence used in manual assertion
Supporting statements:
Nbs1 cardinal features: fused, extended, FHA-BRCT(1)-BRCT(2) domains flexibly linked to C-terminal Mre11- and ATM-binding motifs. 
While spNbs1-fc SAXS closely matches the X-ray structure, the maximum particle dimension (Dmax) for spNbs1-ΔAT is much larger (~175 Å), indicating a very elongated structure (Figures 7A and 7B). Consistent with an unstructured Nbs1 C-terminus, the spNbs1-ΔAT Kratky plot is intermediate between parabolic and asymptotic curves, while spNbs1-fc has a parabolic plot showing spNbs1-fc is folded consistent with proteolysis and crystal structures (Figure 7C).
Although its C-terminus may undergo disorder-to-order transitions upon binding Mre11 and ATM, we do not see stable domains (>10 kDa) when Nbs1 is trypsin digested while in complex with Mre11 (Figure S9). Thus, C-terminal Mre11 and ATM interacting regions may be peptide interaction motifs, rather than globular domains.
Protein: DP02839 (UniProt O43070)
Region: residues 275	to 286
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Nbs1 cardinal features: fused, extended, FHA-BRCT(1)-BRCT(2) domains flexibly linked to C-terminal Mre11- and ATM-binding motifs. 
While no mention is specifically made in text, the region corresponds to a loop that contains a conserved phosphorylation site in both human and yeast Nbs1, and the site is validated in the human protein. both are exposed flexible loops in the structure
Cross-references: PDB:3HUE
Protein: DP02839 (UniProt O43070)
Region: residues 330	to 553
Annotation: molecular adaptor activity (Molecular function)
Evidence: small-angle X-ray scattering evidence used in manual assertion
Supporting statements:
Tethering of Ctp1 to a flexible Nbs1 arm suggests a mechanism for restricting DNA end processing and homologous recombination activities of Sae2/Ctp1/CtIP to the immediate vicinity of DSBs
Nbs1 emerges as an extended, flexible binding nexus coordinating interactions between the Mre11-Rad50 core, the checkpoint kinase ATM/Tel1, and the DNA end-processing factor Ctp1.
Flexible Nbs1 molecular associations may accommodate large-scale MRN complex conformational changes, proposed to regulate ATM activation and dimer-to-monomer transitions
Cross-references: PDB:3HUE
Protein: DP02839 (UniProt O43070)
Region: residues 474	to 531
Annotation: disorder (Structural state)
Evidence: sodium dodecyl sulfate polyacrylamide gel electrophoresis evidence used in manual assertion
Supporting statements:
Figure S2 Legend: Shown are the chromatogram and the SDS–PAGE of fractions containing the Mre11–Nbs1 complex and free Nbs1. The elution volumes and sizes of proteins from a gel filtration standard (Bio–Rad) are noted on top of the chromatogram. 
The SDS-PAGE and SEC profiles shown in Figure S2 indicate that the fragment is disordered in isolation. It has an anomalous migration profile in SDS-PAGE and elutes as a peak of large Rh compared to its MW. The structures also show poor density in the complex with Mre11 at residues: 474-483 and 497-531
Flexible Nbs1 molecular associations may accommodate large-scale MRN complex conformational changes, proposed to regulate ATM activation and dimer-to-monomer transitions
Cross-references: PDB:4FBQ
PDB:4FBK
PDB:4FBW
Protein: DP02839 (UniProt O43070)
Region: residues 477	to 526
Annotation: disorder to order (Structural transition)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
Two Nbs1 subunits stretch around the outside of the nuclease domains of Mre11, with one subunit additionally bridging and locking the Mre11 dimer via a highly conserved asymmetrical binding motif.
Two Nbs1mir molecules wrap around the outside of the two Mre11 phosphodiesterase domains, each binding in a highly extended conformation via a α–helix–β strand motif (Interaction region 1). However, one of the two Nbs1mir molecules additionally binds across the Mre11 dimer interface, forming a second interaction opposite the nuclease cleft (Interaction region 2) (Fig. 2a,b). Consequently, a highly conserved “NFKxFxK motif” (residues 518–526) from one Nbs1mir bridges both copies of the eukaryote–specific loop insertion in the Mre11 dimer.
Cross-references: PDB:4FBQ
PDB:4FBK
PDB:4FBW
Protein: DP02839 (UniProt O43070)
Region: residues 477	to 526
Annotation: protein binding (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
Two Nbs1 subunits stretch around the outside of the nuclease domains of Mre11, with one subunit additionally bridging and locking the Mre11 dimer via a highly conserved asymmetrical binding motif.
Two Nbs1mir molecules wrap around the outside of the two Mre11 phosphodiesterase domains, each binding in a highly extended conformation via a α–helix–β strand motif (Interaction region 1). However, one of the two Nbs1mir molecules additionally binds across the Mre11 dimer interface, forming a second interaction opposite the nuclease cleft (Interaction region 2) (Fig. 2a,b). Consequently, a highly conserved “NFKxFxK motif” (residues 518–526) from one Nbs1mir bridges both copies of the eukaryote–specific loop insertion in the Mre11 dimer.
Cross-references: PDB:4FBQ
PDB:4FBK
PDB:4FBW
Protein: DP02839 (UniProt O43070)
Region: residues 477	to 526
Annotation: molecular adaptor activity (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
Two Nbs1 subunits stretch around the outside of the nuclease domains of Mre11, with one subunit additionally bridging and locking the Mre11 dimer via a highly conserved asymmetrical binding motif.
Two Nbs1mir molecules wrap around the outside of the two Mre11 phosphodiesterase domains, each binding in a highly extended conformation via a α–helix–β strand motif (Interaction region 1). However, one of the two Nbs1mir molecules additionally binds across the Mre11 dimer interface, forming a second interaction opposite the nuclease cleft (Interaction region 2) (Fig. 2a,b). Consequently, a highly conserved “NFKxFxK motif” (residues 518–526) from one Nbs1mir bridges both copies of the eukaryote–specific loop insertion in the Mre11 dimer.
While the mechanistic link between Rad50 and DNA binding to Mre11 requires further studies, our data suggest that Mre11 dimer flexibility and its control by Nbs1 could be an important part of MRN function.
Cross-references: PDB:4FBQ
PDB:4FBK
PDB:4FBW
Protein: DP02840 (UniProt O60934)
Region: residues 272	to 295
Annotation: disorder (Structural state)
Evidence: small-angle X-ray scattering evidence used in manual assertion
Supporting statements:
Yet, structure-based sequence alignments show an insertion missing in the spNbs1-fc model corresponds to an α-helix usually found between the third and fourth BRCT domain β-strands (β17 and β18 of BRCT2), that is linked to an hNbs1 Ser278 phosphorylation site loop (human Nbs1 residues 272–295) (Figure S3). To model these missing regions of hNbs1-fc, we generated 100 hNbs1-fc models based on the spNbs1 structure using MODELLER, and evaluated models by fit to the SAXS data. This approach identified 12 models with superior χ2 fits (χ2<1.3, best model χ2=1.25) that all bear extended accessible pSer278 loop conformations (Figures 2B and 2C). Thus, the overall spNbs1-fc fold is maintained in hNbs1-fc, but is decorated with a solvent-accessible phosphorylated loop. 
(C) Superposition of 12 homology hNbs1 models with SAXS scattering χ2 fits better than 1.3. ATM Phosphorylation sites in hNbs1 map to surface accessible loops with observed conformational variability between models. Ser278 phosphorylation could mediate auto-regulatory BRCT peptide binding in cis through an interaction with the phosphoprotein-binding cleft.
The flexible region includes pSer278 which is a validated site
Protein: DP02840 (UniProt O60934)
Region: residues 276	to 280
Annotation: phosphorylation display site (Disorder function)
Evidence: protein kinase assay evidence used in manual assertion
Supporting statements:
Here we show that phosphorylation of NBS1, induced by ionizing radiation, requires catalytically active ATM. Complexes containing ATM and NBS1 exist in vivo in both untreated cells and cells treated with ionizing radiation. We have identified two residues of NBS1, Ser 278 and Ser 343 that are phosphorylated in vitro by ATM and whose modification in vivo is essential for the cellular response to DNA damage.
To determine whether Ser 278 and Ser 343 of NBS1 are phosphorylated in vivo, NBS1-LBI, a T-antigen immortalized NBS cell line established from a patient carrying the common founder mutation 657del5 (ref. 23) in NBS1, was transfected with plasmids encoding wild-type NBS1 (pCMV-NBS1wt); NBS1S278A (pCMV–NBS1S278A), NBS1S343A (pCMV–NBS1S343A) or NBS1S278A/S343A (pCMV–NBS1S278A/S343A).
Upon treatment with ionizing radiation, the mobility of NBS1wt, but not NBS1S278A, NBS1S343A or NBS1S278A/S343A, was altered ( Fig. 3b, compare lanes 5 and 6 with lanes 3 and 4 and 7–10). These data indicate that Ser 278 and Ser 343 are phosphorylated in vivo.
The pSer278 site is phosphorylated by ATM
Protein: DP02840 (UniProt O60934)
Region: residues 335	to 392
Annotation: disorder (Structural state)
Evidence: cleavage assay evidence used in manual assertion
Supporting statements:
To better understand NBS mutations, we analyzed the human Nbs1-fc structure with SAXS and proteolysis. Human Nbs1 (hNbs1) forms a trypsin-stable composite FHA-BRCT1-BRCT2 core (hNbs1-fc, residues 1-334) similar to spNbs1-fc (Figure 2A)
(A) Trypsin degradation produces a stable hNbs1 folded core (hNbs1-fc, residues 1-334).