LiteFold/DisProt huggingface dataset:
Protein: DP02332 (UniProt Q9BUQ8)
Region: residues 204	to 240
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The Electron Microscopy structure of the human U5.U4/U6 tri-snRNP and human fully-assembled precatalytic spliceosome (pre-B complex), shows this region of the Probable ATP-dependent RNA helicase DDX23 (alternative name Prp28) lacks electron density, indicating it is disordered.
Cross-references: PDB:6QX9
PDB:6QW6
EMDB:EMD-4665
EMDB:EMD-4658
Protein: DP02332 (UniProt Q9BUQ8)
Region: residues 338	to 351
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The final hPrp28ΔN model consists of residues 352–806, five sulfate ions, two glycerol molecules, 3-cyclohexyl-1-propylsulfonic acid, one disordered Hg atom and 220 solvent molecules. Missing residues, namely the N-terminal residues 338–351, loops 695–702 and 724–727 and the C-terminal residues 807–820, resulted from non-interpretable electron density and are most likely to be disordered.
Two loop regions (residues 695–702 and 724–727) as well as the N-terminal residues 338–351 and the C-terminal residues 807–820 are not defined in the electron-density map and are most likely to be disordered.
Cross-references: PDB:4NHO
Protein: DP02332 (UniProt Q9BUQ8)
Region: residues 204	to 219
Annotation: phosphorylation display site (Disorder function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The assignment was only possible by using five- and six-dimensional NMR spectra. Sequence-specific resonance assignment unambiguously identified
phosphorylated serines in the RS repeat stretches comprising residues 204–219 and 242–247.
Sequence-specific resonance assignment of hPrp28 (1–138) phosphorylated by SRPK1 revealed 13 phosphorylation sites including 12 serines and one threonine (Figure 9A). The in vitro phosphorylation pattern is largely consistent with that in
native U5 snRNPs and spliceosomal B complexes (Figure 9B).
(B) Mass spectrometric (MS) determination of phosphorylation sites within the
N-terminal RS domain of hPrp28 in native U5 snRNP (square) and functional
spliceosomal B complex (circle). Phosphorylation sites determined by NMR
after in vitro phosphorylation with SRPK1 are in red letters.
Protein: DP02332 (UniProt Q9BUQ8)
Region: residues 242	to 247
Annotation: phosphorylation display site (Disorder function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The assignment was only possible by using five- and six-dimensional NMR spectra. Sequence-specific resonance assignment unambiguously identified phosphorylated serines in the RS repeat stretches comprising residues 204–219 and 242–247.
Sequence-specific resonance assignment of hPrp28 (1–138) phosphorylated by SRPK1 revealed 13 phosphorylation sites including 12 serines and one threonine (Figure 9A). The in vitro phosphorylation pattern is largely consistent with that in native U5 snRNPs and spliceosomal B complexes (Figure 9B).
(B) Mass spectrometric (MS) determination of phosphorylation sites within the N-terminal RS domain of hPrp28 in native U5 snRNP (square) and functional spliceosomal B complex (circle). Phosphorylation sites determined by NMR after in vitro phosphorylation with SRPK1 are in red letters.
Protein: DP02333 (UniProt P13861)
Region: residues 44	to 90
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Electron microscopy and three-dimensional reconstructions of type-II PKA-AKAP18γ complexes reveal hetero-pentameric assemblies that adopt a range of flexible tripartite configurations. Intrinsically disordered regions within each PKA regulatory subunit impart the molecular plasticity that affords an ∼16 nanometer radius of motion to the associated catalytic subunits.
Protein: DP02333 (UniProt P13861)
Region: residues 44	to 90
Annotation: flexible linker (Disorder function)
Evidence: cryogenic electron microscopy evidence used in manual assertion
Supporting statements:
conformational plasticity observed in these analyses is facilitated by this intrinsically disordered region between residues 44 and 90 of RIIα, a linker that connects the AKAP docking site to the cAMP-responsive transduction domains. This notion is substantiated by a primary sequence analysis of RIIα orthologs, showing that the linker regions are of similar length but exhibit low amino acid identity
Protein: DP02334 (UniProt Q98148)
Region: residues 1110	to 1162
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Our observation of very narrow 1H chemical shift dispersion of merely 0.9 ppm (7.7–8.6 ppm) in the 15N-HSQC spectrum of LANA C-terminal fragment (residues 1110–1162) indicates that this region is unstructured (Figure S1A).
Protein: DP02334 (UniProt Q98148)
Region: residues 1133	to 1144
Annotation: disorder to order (Structural transition)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The structure reveals that the viral peptide establishes a two-strand inter-molecular antiparallel β-sheet with the protein.
Cross-references: PDB:2ND0
BMRB:26042
Protein: DP02334 (UniProt Q98148)
Region: residues 1133	to 1144
Annotation: protein binding (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
We thus constructed a BRD4 ET domain fused at its N-terminus to LANA comprising residues 1110–1162 via a flexible linker (GSGSGS), and determined by NMR analysis that the minimal ET binding site in LANA is confined to residues 1131–1149 (NLQSSIVKFKKPLPLTQPG) (data not shown). Notably, the 15N-HSQC spectra of the ET domain displayed nearly identical protein backbone resonance perturbation patterns induced by adding a LANA segment consisting of residues 1110–1162 or 1131–1149 (Figure S1A), or a LANA peptide of residues 1133–1144 (Figure 1B, red vs. blue signals), thereby defining the ET domain binding site in LANA to residues 1133–1144. We further determined binding affinity of the ET domain to the LANA peptide by NMR titration to be approximately Kd = 635 μM (Figure S1A).
Cross-references: BMRB:26042
PDB:2ND0
Protein: DP02334 (UniProt Q98148)
Region: residues 745	to 925
Annotation: disorder (Structural state)
Evidence: curator inference from database used in manual assertion
Supporting statements:
This poly-E region is inferred by the curator to be disordered, based on MobiDB-Lite and according to experimental evidence demonstrating that poly-E repeats display random-coil-like conformation (PMID:16949547)
Protein: DP02334 (UniProt Q98148)
Region: residues 620	to 723
Annotation: disorder (Structural state)
Evidence: curator inference from database used in manual assertion
Supporting statements:
This poly-E region is inferred by the curator to be disordered, based on MobiDB-Lite and according to experimental evidence demonstrating that poly-E repeats display random-coil-like conformation (PMID:16949547)
Protein: DP02334 (UniProt Q98148)
Region: residues 325	to 426
Annotation: disorder (Structural state)
Evidence: curator inference from database used in manual assertion
Supporting statements:
This poly-E region is inferred by the curator to be disordered, based on MobiDB-Lite and according to experimental evidence demonstrating that poly-E repeats display random-coil-like conformation (PMID:16949547)
Protein: DP02334 (UniProt Q98148)
Region: residues 1133	to 1144
Annotation: viral life cycle (Biological process)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
We thus constructed a BRD4 ET domain fused at its N-terminus to LANA comprising residues 1110–1162 via a flexible linker (GSGSGS), and determined by NMR analysis that the minimal ET binding site in LANA is confined to residues 1131–1149 (NLQSSIVKFKKPLPLTQPG) (data not shown). Notably, the 15N-HSQC spectra of the ET domain displayed nearly identical protein backbone resonance perturbation patterns induced by adding a LANA segment consisting of residues 1110–1162 or 1131–1149 (Figure S1A), or a LANA peptide of residues 1133–1144 (Figure 1B, red vs. blue signals), thereby defining the ET domain binding site in LANA to residues 1133–1144. We further determined binding affinity of the ET domain to the LANA peptide by NMR titration to be approximately Kd = 635 μM (Figure S1A).
Cross-references: PDB:2ND0
BMRB:26042
Protein: DP02337 (UniProt O46385)
Region: residues 1	to 342
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
An N-terminal, 830-residue Intrinsically Disordered Region of the Cytoskeleton-regulatory Protein Supervillin Contains Myosin II- and F-actin- Binding Sites
Here, we utilize Circular Dichroism (CD) and bioinformatics sequence analysis to demonstrate that the N-terminal part of supervillin forms an extended intrinsically disordered region (IDR). Our combined data indicate that the N-terminus of human and bovine supervillin sequences (positions 1–830) represents an intrinsically disordered region, which is the largest IDR known to date in the villin/gelsolin family. Moreover, this result suggests a potentially novel mechanism of regulation of myosin II and F-actin via the intrinsically disordered N-terminal region of hub protein supervillin.
Major cytoskeletal interactors, including filamentous actin and myosin II, bind within the unique supervillin amino terminus, amino acids 1-830.
Here, we present CD spectra and bioinformatics analyses to show that this region of supervillin is predominately disordered in the unbound state.
Furthermore, the incidence of charged side chains within residues 1–830 is also somewhat higher in the N-terminus of supervillin than in its C-terminus or in villin and gelsolin. These hydrophobicity-charge features of the supervillin N-terminus are typical for intrinsically disordered proteins (IDP), which lack the capacity to fold in an aqueous solvent
This N-terminal disordered region of bovine supervillin interacts with at least 17 proteins.
Based on the disordered nature of the N-terminus, we can propose certain features of the mechanisms of binding of F-actin and myosin II by supervillin. Its sequence M binds the S2 fragment of nonmuscle and smooth muscle myosin II, whereas fragments A1, A2 and A3 bind F-actin
Our CD data indicate that the first 342 residues of supervillin form an intrinsically disordered region. The complementary bioinformatics analysis suggests that the entire N-terminus of supervillin likely represents a large IDR.
Protein: DP02337 (UniProt O46385)
Region: residues 11	to 174
Annotation: protein binding (Molecular function)
Evidence: yeast 2-hybrid evidence used in manual assertion
Supporting statements:
Minimal sequences required for the binding to myosin II are supervillin amino acids 11-174 and sequences within myosin subdomain S2.
Protein: DP02337 (UniProt O46385)
Region: residues 11	to 174
Annotation: protein binding (Molecular function)
Evidence: co-sedimentation assay evidence used in manual assertion
Supporting statements:
Supervillin sequences capable of binding to actin filaments include a site near the C terminus of SV-(171-342), the N terminus of SV-(343-571), and the C terminus of SV-(570-830) (Fig. 2C).
Similar amounts of co-sedimentation with F-actin were observed for SV-(343-571) as for SV-(171-342) and SV-(570-830) (Fig. 2A), each of which contains a single C-terminal actin-binding site (Fig. 2C).
F-actin binds independently and directly to three regions of supervillin (SV-(171-342), SV-(343-571), and SV570-830)).
Protein: DP02337 (UniProt O46385)
Region: residues 1	to 342
Annotation: molecular adaptor activity (Molecular function)
Evidence: fluorescence microscopy evidence used in manual assertion
Supporting statements:
Overexpression of supervillin amino acids 1-174 in COS7 cells disrupted the localization of myosin IIB without obviously affecting actin filaments. Taken together, these results suggest that supervillin may mediate actin and myosin II filament organization at cholesterol-rich membrane domains.
Minimal sequences required for the binding to myosin II are supervillin amino acids 11-174 and sequences within myosin subdomain S2.
F-actin binds independently and directly to three regions of supervillin (SV-(171-342), SV-(343-571), and SV570-830)).
Supervillin sequences capable of binding to actin filaments include a site near the C terminus of SV-(171-342), the N terminus of SV-(343-571), and the C terminus of SV-(570-830) (Fig. 2C).
Similar amounts of co-sedimentation with F-actin were observed for SV-(343-571) as for SV-(171-342) and SV-(570-830) (Fig. 2A), each of which contains a single C-terminal actin-binding site (Fig. 2C).
Protein: DP02338 (UniProt O60701)
Region: residues 465	to 494
Annotation: flexible C-terminal tail (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Here we show that the entropic force produced by an ID carboxy-terminus (ID-tail) shifts the conformational ensemble of human UDP-α-D-glucose-6-dehydrogenase (hUGDH) toward a substate with a high affinity for an allosteric inhibitor.
The function of the ID-tail does not depend on its sequence or chemical composition. Instead, the affinity enhancement can be accurately predicted based on the length of the ID segment and is consistent with the entropic force generated by an unstructured peptide attached to the protein surface
Our data show that the unfolded state of the ID-tail rectifies the dynamics and structure of hUGDH to favor inhibitor binding
For example, the 30-residue disordered C-terminus of hUGDH (residues 465–494) is often removed with no apparent impact on kinetic parameters19. Here, we show that this C-terminal segment (called the ‘ID-tail’) plays a novel role in the allosteric mechanism of hUGDH. hUGDH catalyzes the NAD+-dependent oxidation of UDP-α-D-glucose (UDP-Glc) to UDP-α-D-glucuronic acid19 and is regulated by the allosteric feedback inhibitor UDP-α-D-Xylose (UDP-Xyl)
We used the allostery quenching A136M substitution to see if the ID-tail functions independently of the allosteric switch; this substitution has been shown to lock the allosteric switch and the hexamer in the low UDP-Xyl affinity, E state22. Inhibition studies show no significant difference in UDP-Xyl affinity between hUGDHFL-A136M and hUGDHΔID-A136M, which suggests that the ID-tail requires a functional allosteric switch and the EΩ state to enhance the affinity for UDP-Xyl
the ID-tail functions as a length-dependent (l) entropic rectifier that biases (k) the distribution toward the high affinity substate
Cross-references: PDB:5VR8
Protein: DP02338 (UniProt O60701)
Region: residues 465	to 494
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
For example, the 30-residue disordered C-terminus of hUGDH (residues 465–494) is often removed with no apparent impact on kinetic parameters19.
The PDB structure shows this region lacks electron density indicating it is disordered. 
Cross-references: PDB:5VR8
Protein: DP02341 (UniProt A0A178W0D3)
Region: residues 221	to 259
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
To ascertain whether Vc represents an IDR or not, circular dichroism (CD) spectra of a synthetic peptide precisely corresponding to Vc (38 amino acids) were examined. A large negative peak at approximately 202 nm is characteristic to the coil conformation that dominates in disordered proteins. The minimum spectrum of Vc at around 200 nm typically showed the property of IDR.
Protein: DP02341 (UniProt A0A178W0D3)
Region: residues 221	to 259
Annotation: disorder (Structural state)
Evidence: temperature-induced protein unfolding evidence used in manual assertion
Supporting statements:
The ellipticity at 202 nm was monitored upon increasing the temperature, and was found to increase gradually. However, the lack of an obvious thermal transition indicated that Vc does not take a prominent secondary structure. In addition, the slight CD spectral change was reversible.
Protein: DP02341 (UniProt A0A178W0D3)
Region: residues 221	to 259
Annotation: protein folding chaperone (Molecular function)
Evidence: temperature-induced protein unfolding evidence used in manual assertion
Supporting statements:
Vc (VIPP1 C-terminal tail) acts in promoting flexible mobility against stress by preventing self-association of FVPs; and the elevated expression of VIPP1 improves the tolerance of chloroplasts against heat shock. Dynamic movement of VIPP1 upon stress is a prerequisite for such tolerance,
Protein: DP02342 (UniProt P06837)
Region: residues 1	to 227
Annotation: pre-molten globule (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
CD spectra of Nm and Ng showed an intense minimum at 201 and 204 nm respectively, indicating the presence of disordered regions in these proteins. The CD analysis further supports that Nm and Ng both have residual secondary structural elements (mainly α-helix) and suggests that these two proteins exist in a premolten globular conformational state of protein quartet model under physiological conditions (Supplementary Figure 2A).
Protein: DP02342 (UniProt P06837)
Region: residues 34	to 57
Annotation: localization (Biological process)
Evidence: isothermal titration calorimetry evidence used in manual assertion
Supporting statements:
One proposed biochemical function of Nm and Ng is to target CaM at the membrane in the vicinity of ‘CaM-activated enzymes’ under low Ca2+ conditions at the pre- and post-synaptic terminals, respectively1,22,24. Therefore, Nm and Ng might serve as a Ca2+-regulated modulators of CaM activity in neurons.
Protein: DP02342 (UniProt P06837)
Region: residues 34	to 57
Annotation: molecular function regulator (Molecular function)
Evidence: isothermal titration calorimetry evidence used in manual assertion
Supporting statements:
One proposed biochemical function of Nm and Ng is to target CaM at the membrane in the vicinity of ‘CaM-activated enzymes’ under low Ca2+ conditions at the pre- and post-synaptic terminals, respectively1,22,24. Therefore, Nm and Ng might serve as a Ca2+-regulated modulators of CaM activity in neurons.
Protein: DP02342 (UniProt P06837)
Region: residues 1	to 227
Annotation: pre-molten globule (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The NMR spectra of full-length Nm and Ng were very similar to those previously observed for other unstructured proteins (Supplementary Figures 2B and 2C). The resonance of both protein's methyl group protons (at 0.9 and 0.95 ppm) and amide groups (around 8.4 ppm), along with very limited spectral dispersion of these signals, indicated the lack of a stable tertiary structure in both Nm and Ng
Nm and Ng have a low percentage of order-promoting amino acids and high percentage of disorder-promoting amino acids (Supplementary table 1). The acidic pI and low hydrophobicity of these two proteins indicates that they are unfolded (See supplementary text). Besides, gel filtration chromatography and Dynamic Light Scattering experiments show the higher hydrodynamic radii and molecular weight for both Nm and Ng (See supplementary text). Thus, the biophysical studies on Nm and Ng support the classification of these proteins as intrinsically unstructured, lacking a compact globular fold, and having very little secondary structure27,28,29.
Protein: DP02342 (UniProt P06837)
Region: residues 34	to 57
Annotation: protein binding (Molecular function)
Evidence: isothermal titration calorimetry evidence used in manual assertion
Supporting statements:
ITC experiments revealed that the full-length Nm and Ng bind to apo CaM (in the absence of Ca2+) with a higher affinity than that to Ca2+/CaM. These observations are consistent with the previous fluorescence experiments1 (Table 1). Further, the ITC results show that NmIQ and NgIQ peptides have a similar affinity toward apo CaM as their full-length counterparts; thus, the IQ peptides almost mimic their full-length proteins. Nm and Ng interacted with CaM mainly through their IQ motifs with a stoichiometric ratio of 1[ratio]1.
Protein: DP02342 (UniProt P06837)
Region: residues 34	to 57
Annotation: protein binding (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
Here, we report the structure of IQ peptides (24aa) of Nm/Ng complexed with CaM and their functional studies with full-length proteins. Nm/Ng and their respective IQ peptides are intrinsically unstructured; however, upon binding with CaM, IQ motifs adopt a helical conformation.
Protein: DP02342 (UniProt P06837)
Region: residues 34	to 57
Annotation: pre-molten globule to order (Structural transition)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
In summary, this is the first report of the crystal structure of the intrinsically unstructured, neuron-specific substrate proteins, Nm/Ng, as IQ peptides in complex with CaM. The unstructured IQ peptides (24 aa) interact with the C-lobe of CaM and gain an α-helical conformation
Nm/Ng and their respective IQ peptides are intrinsically unstructured; however, upon binding with CaM, IQ motifs adopt a helical conformation. Ser41 (Ser36) of Nm (Ng) is located in a negatively charged pocket in the apo CaM and, when phosphorylated, it will repel Nm/Ng from CaM
Cross-references: PDB:4E53
Protein: DP02345 (UniProt Q92804)
Region: residues 323	to 354
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Architecturally, TAF15 is composed of an intrinsically unstructured N-terminal QGSY rich activation domain which is retained in the oncogenic fusions and possesses trans-activating properties, followed by a central and the C-terminal region comprising the RNA recognition motif (RRM) and a (Cys)4 RanBP2 type Zinc finger (ZnF) with interspersed unstructured elements rich in arginine and glycine, known as RGG motifs. The RRM exhibits highest degree of sequence conservation among the members of the FET family.
15N-{1H} Het-NOE values, corresponding to an average of ~0.75 in the RRM and ZnF domains, and ~0.38 in the RGG linker, indicated the presence of highly dynamic linker between the structured RRM and the RanBP2 type ZnF domain in the multi-domain protein
Moreover, random coil index analysis (RCI) of the backbone32 revealed the absence of any secondary structural elements between E323-K354, which constitute the RGG motif.
conclusively establish the predominant role played by RRM in mediating RNA binding and negate any significant contributions toward RNA recognition by the RGG motifs and the RanBP2 type zinc finger
Very few residues in the RGG motif (E323-R326 and G342), and the RanBP2 type zinc finger domain (S355, F370-R372) exhibited CSPs above the averaged CSP + 1σ (Fig. 2C). The CSPs in E323-R326 region can be explained from its existence as an extension of the C-terminal region of the RRM, which may provide additional contributions in stabilizing the complex. Despite these additional contributions, N- or C-terminal extensions in an RRM have been rarely shown to provide specificity in recognition