LiteFold/DisProt huggingface dataset:
Protein: DP01476 (UniProt Q02413)
Region: residues 774	to 1049
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Here, we reveal that a 276-residue DSCR construct of human desmoglein 1 is intrinsically disordered and forms an interaction hub for desmosomal proteins. In solution, it contains 6.5% helical and 10.3% beta-strand structure based on circular dichroism spectroscopy. A single monomeric state with a predominantly unfolded structure is found by size-exclusion chromatography and analytical ultracentrifugation. Thermal stability assays and nuclear magnetic resonance spectroscopy reveal a nonglobular structure under a range of solution conditions.
Results from nuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopy demonstrate that the DSCR of human Dsg1 is intrinsically disordered in solution, having little intrinsically stable structure but with inducible conformations that can be stabilized by co-solvents and micelles. Analysis of its hydrodynamic behavior demonstrates that the protein exists as a monomer and in an unfolded conformation rather than a globular form.
In contrast, the NMR signals of the DSCR were not well dispersed, with narrow, intense, and overlapped methyl proton resonances at random-coil values of 0.8 to 1.0 ppm. The backbone amide protons are almost entirely clustered between 7.9 and 8.5 ppm, with only two downfield peaks discernable at 8.70 and 9.21 ppm. The DSCR's sole Trp appeared disordered, exhibiting random-coil NɛH chemical shifts of 10.05 and 10.24 ppm, presumably due to the apparent cis–trans isomerization of its neighboring proline residues (Fig. 4). Together, this indicates a disordered region lacking in stable tertiary structure and is consistent with the largely unfolded conformation of the DSCR based on its hydrodynamic properties.
The limited dispersion of chemical shifts in the NMR spectrum confirms the absence of stable, three-dimensional structure.
Protein: DP01476 (UniProt Q02413)
Region: residues 774	to 1049
Annotation: protein binding (Molecular function)
Evidence: bait-prey hybrid interaction evidence used in manual assertion
Supporting statements:
Thus, the DSCR is an intrinsically disordered functional domain with an inducible structure that, along with the membrane proximal region, forms a flexible scaffold for cytoplasmic assembly at the desmosome.
We conclude that the DSCR forms an intrinsically disordered state in solution with inducible structure that, together with the MPR, forms a hub for multiple protein interactions during desmosomal cell adhesion.
These data suggest that the entire DSCR is required for its interaction with its desmosomal protein partners and forms a single functional unit that can be regulated by caspase cleavage.
Coomassie-stained GST-fused desmosomal proteins used in pull-down assays. GST-PG, GST fused to full-length PG; GST-DP, GST fused to the plakin domain of DP (residues 10–1097); GST-PKP1, GST fused to residues 6–726 of PKP1; GST-Dsc1, GST fused to the cytoplasmic domain of Dsc1 (residues 717–894).
Overall, the pull-down assays suggest that the entire Dsg1 cytoplasmic domain (i.e., MPR + DSCR) acts as a flexible scaffold for cytoplasmic complex assembly at the desmosome with a network of strong and weak protein–protein interactions.
The intrinsic plasticity of such intrinsically disordered regions is often used to mediate interactions with multiple biological targets. Indeed, this would appear to be the case for the DSCR as pull-down assays show that it is able to interact with multiple partners including PG, the plakin domain of DP, PKP1, and the cytoplasmic domain of Dsc1.
We suggest that strong interactions between some cytoplasmic desmosomal proteins (e.g., MPR and PG/PKP1) are supported by a network of weaker interactions between others (MPR and DP/Dsc1; DSCR and PG/PKP1/DP/Dsc1). This web of interactions places the desmoglein cytoplasmic domain at the heart of the desmosomal complex, thus enabling it to play important role in desmosome assembly and intercellular adhesion.
Protein: DP01478 (UniProt Q9UJX5)
Region: residues 304	to 317
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Table 4 of the paper
Cross-references: PDB:5BPW
Protein: DP01478 (UniProt Q9UJX5)
Region: residues 431	to 444
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Table 4 of the paper
Cross-references: PDB:5BPW
Protein: DP01478 (UniProt Q9UJX5)
Region: residues 458	to 472
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Table 4 of the paper
Cross-references: PDB:5BPW
Protein: DP01478 (UniProt Q9UJX5)
Region: residues 458	to 469
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The region is specified in the Extended Data Table 2
Cross-references: PDB:4UI9
PDB:5A31
PDB:5G05
PDB:5G04
Protein: DP01478 (UniProt Q9UJX5)
Region: residues 758	to 808
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The region is specified in the Extended Data Table 2
Cross-references: PDB:4UI9
PDB:5A31
PDB:5G05
PDB:5G04
Protein: DP01478 (UniProt Q9UJX5)
Region: residues 480	to 521
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Table 4 of the paper
Cross-references: PDB:5BPW
Protein: DP01478 (UniProt Q9UJX5)
Region: residues 758	to 808
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Authors said ".. C-terminal residues (758–808) of human Apc4 are disordered in both the crystal structure and the EM density map."
Cross-references: PDB:5BPW
Protein: DP01479 (UniProt Q9UJX3)
Region: residues 77	to 97
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The region is specified in the Extended Data Table 2
Cross-references: PDB:4UI9
Protein: DP01479 (UniProt Q9UJX3)
Region: residues 77	to 96
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
See region in Table 4
Protein: DP01479 (UniProt Q9UJX3)
Region: residues 507	to 565
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The region is specified in the Extended Data Table 2
Cross-references: PDB:4UI9
Protein: DP01480 (UniProt Q96FI4)
Region: residues 312	to 389
Annotation: disorder (Structural state)
Evidence: small-angle X-ray scattering evidence used in manual assertion
Supporting statements:
Small-angle X-ray scattering (SAXS) analysis confirms the flexibility and dynamic nature of NEIL1's CTD, a feature that may be critical to providing specificity for NEIL1's multiple, functional interactions.
Cross-references: SASBDB:SASDBC7
SASBDB:SASDBB7
SASBDB:SASDBA7
Protein: DP01480 (UniProt Q96FI4)
Region: residues 312	to 389
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
The CD spectrum of NEIL1's C-terminal 78-residue peptide (amino acids 312–389; C78) reveals a prominently disordered structure with random-coil conformation.
Protein: DP01481 (UniProt Q5UPT2)
Region: residues 1	to 94
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
To evaluate the secondary structure of the invisible segment in the N-domain, we compared the CD spectra of mvUNG and mvUNG95-370. In the far-UV CD spectra, the deletion of residues 1–94 did not change the pattern and scale of the CD spectrum in the range between 210–250 nm, indicating that residues 1–94 have a random coil conformation.
Protein: DP01481 (UniProt Q5UPT2)
Region: residues 1	to 94
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
A solvent space that could accommodate residues 1–94 was insufficient in the crystal.
In contrast to the structured part of the N-domain and the motif-I, residues 1–94 in N-domain are not included in the crystal structure of mvUNG. They seem to be truncated before crystallization. Indeed, all reported crystal structures of UNG proteins display only a catalytic domain.
Cross-references: PDB:5X55
Protein: DP01481 (UniProt Q5UPT2)
Region: residues 1	to 94
Annotation: uracil DNA N-glycosylase activity (Molecular function)
Evidence: enzymatic activity assay evidence used in manual assertion
Supporting statements:
Activity assays and CD spectra implied that the unstructured segment (residues 1–94) in the N-domain also contributes to thermal stability and catalytic activity of mvUNG.
It seems to contribute to diverse cellular functions of UNGs. For example, the N-domain of hUNG is involved in the subcellular localization of isoforms [39] and the interaction with the DNA repair factor RPA [40, 41]. In the activity assay of the N-domain deletion mutants, mvUNG95-370 which residues 1–94 is deleted showed 55% activity, compared with full-length mvUNG (first and third bars in Fig 4b). Additional deletion of residues 95–121 reduced the activity to 15%, even though the deletion mutant contains the entire catalytic domain (first and fourth bars in Fig 4b). This result indicated that both invisible (residues 1–94) and visible (residues 95–130) segments of the N-domain are required for the intrinsic activity of mvUNG.
Protein: DP01481 (UniProt Q5UPT2)
Region: residues 1	to 94
Annotation: uracil DNA N-glycosylase activity (Molecular function)
Evidence: deletion mutation phenotypic evidence used in manual assertion
Supporting statements:
Activity assays and CD spectra implied that the unstructured segment (residues 1–94) in the N-domain also contributes to thermal stability and catalytic activity of mvUNG.
It seems to contribute to diverse cellular functions of UNGs. For example, the N-domain of hUNG is involved in the subcellular localization of isoforms [39] and the interaction with the DNA repair factor RPA [40, 41]. In the activity assay of the N-domain deletion mutants, mvUNG95-370 which residues 1–94 is deleted showed 55% activity, compared with full-length mvUNG (first and third bars in Fig 4b). Additional deletion of residues 95–121 reduced the activity to 15%, even though the deletion mutant contains the entire catalytic domain (first and fourth bars in Fig 4b). This result indicated that both invisible (residues 1–94) and visible (residues 95–130) segments of the N-domain are required for the intrinsic activity of mvUNG.
Protein: DP01482 (UniProt O13828)
Region: residues 553	to 741
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
In addition, the C-terminal extension is predicted to be unstructured in isolation, which is confirmed by NMR spectra of Dcp2 residues 553–741 (Supplementary Figure S6A).
Protein: DP01482 (UniProt O13828)
Region: residues 553	to 741
Annotation: protein binding (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Spectrum of Dcp2 residues 553-741 without (green, as in A) and with the Edc3 LSm domain (blue). The increase in chemical shift dispersion and the appearance of new resonances (e.g. red circle) indicates the formation of secondary structure upon the complex formation between the Dcp2 C-terminal tail and the NMR inactive Edc3 LSm domain.
Protein: DP01482 (UniProt O13828)
Region: residues 553	to 741
Annotation: disorder to order (Structural transition)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Spectrum of Dcp2 residues 553-741 without (green, as in A) and with the Edc3 LSm domain (blue). The increase in chemical shift dispersion and the appearance of new resonances (e.g. red circle) indicates the formation of secondary structure upon the complex formation between the Dcp2 C-terminal tail and the NMR inactive Edc3 LSm domain.
In the reverse experiment, we probed the effect of the Edc3 LSm domain addition on the spectrum of the disordered 15N-labelled Dcp2 C-terminal residues. As expected, we clearly observed binding and resonances indicative of α-helical structure appeared (Supplementary Figure S6B). This shows that the leucine-rich motifs in the disordered Dcp2 C-terminus fold into an α-helical conformation when interacting with the Edc3 LSm domains, as we observed for the HLM-1 sequence.
Protein: DP01482 (UniProt O13828)
Region: residues 246	to 266
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 spDcp2n was determined by SAD at a resolution of 2.5 Å. The final model contains two molecules (A and B) in the asymmetric unit. Several regions of the polypeptide chain are not visible in the electron density map and are assumed to be disordered, namely residues 79–81, 186–191, 209–214 and 246–266 for molecule A and residues 1–34, 55–57, 69–82, 116–122, 186–191, 209–214 and 244–266 for molecule B.
Protein: DP01484 (UniProt P04626)
Region: residues 988	to 1255
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Here we report backbone and side-chain assignment of CtErbB2, which, together with structural predictions, confirms its intrinsically disordered nature.
The sequence of the studied protein fragment and its 1H-15N 2D HSQC spectrum are shown in Fig. 1. The low dispersion of amide-proton chemical shifts is characteristic of a highly disordered domain, as expected from the high proline, high charged residue and low hydrophobic content of the sequence.
Protein: DP01484 (UniProt P04626)
Region: residues 988	to 1255
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
Circular dichroism of CtErbB2 was measured at298 K and shows the characteristic signature of an IDP, with only one strong negative band at 200 nm (Fig.1B). Small angleX-ray scattering (SAXS) also supports this observation.
Protein: DP01484 (UniProt P04626)
Region: residues 988	to 1255
Annotation: disorder (Structural state)
Evidence: small-angle X-ray scattering evidence used in manual assertion
Supporting statements:
However, ErbB2 disordered C-terminal cytoplasmic tail (CtErbB2) remains very poorly characterized in terms of structure, dynamics and detailed functional mechanism. Yet, it is where signal transduction is triggered, via phosphorylation of tyrosine residues, and carried out, via interaction with adaptor proteins. Here we report the first description of ErbB2 disordered tail at atomic resolution using NMR, complemented by SAXS.
The scattering curve of CtErbB2 is given in Fig.1C. The Kratky plot and the distance distribution are characteristic of a disordered protein, giving a radius of gyration of 49.2 Å from the P(r) distribution. Flory theory gives the radius of gyration Rg of a polymer with N monomers, Rg=R0Nν, where R0 and ν depend on the behavior of the polymer in solution, and especially its solvation. Its applicability to denatured or disordered proteins has already been investigated
Protein: DP01484 (UniProt P04626)
Region: residues 988	to 1255
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
However, ErbB2 disordered C-terminal cytoplasmic tail (CtErbB2) remains very poorly characterized in terms of structure, dynamics and detailed functional mechanism. Yet, it is where signal transduction is triggered, via phosphorylation of tyrosine residues, and carried out, via interaction with adaptor proteins. Here we report the first description of ErbB2 disordered tail at atomic resolution using NMR, complemented by SAXS.
At atomic resolution, the poor dispersion of CtErbB2 proton resonances in the1H-15N HSQC spectrum is typical of an intrinsically disordered protein (Fig.1D).
Moreover, backbone N-H residual dipolar couplings (RDCs) measured in stretched acrylamide gels (1DN H, Fig.2A) are negative almost all along CtErbB2 sequence,as usually observed for denatured or disordered proteins (59,60). Overall, all the data show that CtErbB2 is an intrinsically disordered region (IDR).
Protein: DP01485 (UniProt P40161)
Region: residues 43	to 67
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Residues 43-67 are disordered (red) and constitute the flexible linker to the tandem PH domains.
Protein: DP01485 (UniProt P40161)
Region: residues 43	to 67
Annotation: flexible linker (Disorder function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Residues 43-67 are disordered (red) and constitute the flexible linker to the tandem PH domains.
Protein: DP01486 (UniProt P11912)
Region: residues 166	to 226
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
CD analysis of shows the characteristics of intrinsically unstructured proteins at both concentrations.
Protein: DP01487 (UniProt P40259)
Region: residues 181	to 229
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
CD analysis of  shows the characteristics of intrinsically unstructured proteins at both concentrations.
Protein: DP01488 (UniProt P69346)
Region: residues 1	to 83
Annotation: disorder (Structural state)
Evidence: cleavage assay evidence used in manual assertion
Supporting statements:
Analysis of YefM levels in E. coli, before and after repression at different intervals, reveals that the YefM antitoxin is proteolytically unstable.
Protein: DP01488 (UniProt P69346)
Region: residues 1	to 83
Annotation: disorder (Structural state)
Evidence: Fourier-transform infrared spectroscopy evidence used in manual assertion
Supporting statements:
FTIR spectroscopy also indicates that YefM protein is random coil-structured.
Protein: DP01488 (UniProt P69346)
Region: residues 1	to 83
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
The far-UV CD spectra of the purified YefM protein show a typical random coil pattern.
Protein: DP01488 (UniProt P69346)
Region: residues 11	to 23
Annotation: protein binding (Molecular function)
Evidence: surface plasmon resonance evidence used in manual assertion
Supporting statements:
SPR analysis was used to quantitative determine the affinity between the YoeB toxin and the YefM11–23 peptide fragment.
an equilibrium constant (KD) of 0.4 microM was determined for the YoeB-YefM11–23complex. This dissociation constant is consistent with a specific binding between the toxin and the peptide fragment.
Protein: DP01488 (UniProt P69346)
Region: residues 56	to 83
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The N-terminal segments of the two YefM monomers form a symmetrical dimer. One of the YefM C-terminal segments (H4–S4) extending from the N-terminal dimer exclusively binds the globular YoeB monomer. The other YefM C terminus is structurally disordered.
Cross-references: PDB:2A6Q
Protein: DP01488 (UniProt P69346)
Region: residues 1	to 83
Annotation: disorder to order (Structural transition)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
The difference in behavior indicates that the polypeptide region from the end of the H3 helix to the C terminus is a random coil in the absence of a binding target, and undergoes a disorder-to-order transition upon binding YoeB.
Cross-references: PDB:2A6Q
Protein: DP01488 (UniProt P69346)
Region: residues 1	to 83
Annotation: protein binding (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
The difference in behavior indicates that the polypeptide region from the end of the H3 helix to the C terminus is a random coil in the absence of a binding target, and undergoes a disorder-to-order transition upon binding YoeB.
One of the YefM C-terminal segments (H4–S4) extending from the N-terminal dimer exclusively binds the globular YoeB monomer.
Cross-references: PDB:2A6Q
Protein: DP01488 (UniProt P69346)
Region: residues 1	to 55
Annotation: protein binding (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
The N-terminal segments of the two YefM monomers form a symmetrical dimer.
Cross-references: PDB:2A6Q
Protein: DP01488 (UniProt P69346)
Region: residues 1	to 83
Annotation: disorder (Structural state)
Evidence: temperature-induced protein unfolding evidence used in manual assertion
Supporting statements:
YefM  remains  soluble  through  boiling.
Protein: DP01489 (UniProt Q9UBK2)
Region: residues 2	to 220
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy-based hydrogen-deuterium exchange evidence used in manual assertion
Supporting statements:
HDX analysis of PGC1α220 revealed that most of the backbone amides were fully exchanged after 10 s incubation with deuterium, consistent with the predicted disorder.
Protein: DP01489 (UniProt Q9UBK2)
Region: residues 2	to 220
Annotation: disorder (Structural state)
Evidence: analytical ultracentrifugation evidence used in manual assertion
Supporting statements:
SV analysis at 4 °C yields a frictional coefficient ratio (f∕f o) of 2.7 (a globular particle has an f∕f o of approximately 1.2, whereas a value greater than 1.8 indicates asymmetry in shape), indicating an extremely elongated shape.
Protein: DP01489 (UniProt Q9UBK2)
Region: residues 2	to 220
Annotation: disorder to order (Structural transition)
Evidence: analytical ultracentrifugation evidence used in manual assertion
Supporting statements:
The reduction in f∕f 0 between PGC1α220 and the binary complex (2.0 versus 1.5) is suggestive of coactivator compaction upon complex formation.
Protein: DP01489 (UniProt Q9UBK2)
Region: residues 2	to 220
Annotation: disorder (Structural state)
Evidence: chromatography evidence used in manual assertion
Supporting statements:
Despite being monomeric by mass as indicated by SEC-MALS, a Stokes radius of Rs of 42.9 Å  0.46 was determined, indicative of a molten-globular, extended conformation in solution.
Protein: DP01489 (UniProt Q9UBK2)
Region: residues 2	to 220
Annotation: disorder (Structural state)
Evidence: small-angle X-ray scattering evidence used in manual assertion
Supporting statements:
This low level of compactness is further underscored by an Rs/Rg value of approximately 1.45 for PGC1α220, similar to that expected for a random coil. The Kratky and Porod–Debye plots (22–26) for PGC1α220 are clearly indicative of a largely disordered species lacking a well-packed core.