LiteFold/DisProt huggingface dataset:
Protein: DP03560 (UniProt P20879)
Region: residues 42	to 54
Annotation: nucleosome binding (Molecular function)
Evidence: bait-prey hybrid interaction evidence used in manual assertion
Supporting statements:
The results of such an experiment are shown in Fig. 7B, where acetylated Tat peptide was able to bind to core histones. It is interesting to note that core histones in the absence of DNA did not bind to acetylated Tat, indicating that a fixed conformation of nucleosome is required for Tat to bind to core histones.
Protein: DP03560 (UniProt P20879)
Region: residues 48	to 57
Annotation: histone acetyltransferase binding (Molecular function)
Evidence: glutathione S-transferase pull-down assay evidence used in manual assertion
Supporting statements:
Only fusion proteins which contained the Tat basic domain (residues 48 to 57) bound p300, including a fusion protein that expressed only this basic domain region (Fig. ​4A, top).
Protein: DP03562 (UniProt P04613)
Region: residues 1	to 87
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
In aqueous buffer (Fig. 4 A), it can be deduced from the intensity of the negative 200 nm band that nonorganized structures are predominant (29). TableI reveals that there is no α helix in aqueous buffer excepted for Tat Mal and Tat Z2, which could have a short helix of eight to nine residues.
Protein: DP03562 (UniProt P04613)
Region: residues 1	to 87
Annotation: regulatory region RNA binding (Molecular function)
Evidence: electrophoretic mobility shift assay evidence used in manual assertion
Supporting statements:
The K d values vary from approximately 50 nm for both Tat Eli and Tat Mal to about 140 nmfor Tat Oyi and Tat JR.
The six synthetic Tat proteins can bind to TAR RNA (Fig.3) and can inhibit PKR (data not shown).
Protein: DP03562 (UniProt P04613)
Region: residues 1	to 87
Annotation: viral gene expression (Biological process)
Evidence: beta-galactosidase reporter gene assay evidence used in manual assertion
Supporting statements:
In each case, Tat was added to the cell buffer, and therefore expression of β-gal up to the control means that the synthetic Tat was able to cross the cytoplasmic and nucleus membranes, bind TAR, and interact with cellular cofactors.
Tat Mal and Tat Eli show a level of trans-activation three to four times higher to that of Tat Bru.
The major result of trans-activation tests was the high activity of Tat Mal and Tat Eli, which correlates with the high virulence of these two HIV-1 isolates.
Protein: DP03562 (UniProt P04613)
Region: residues 1	to 87
Annotation: viral gene expression (Biological process)
Evidence: luciferase reporter gene assay evidence used in manual assertion
Supporting statements:
Similar results were obtained with another transfection assay using luciferase as gene reporter, and Tat Mal and Tat Eli at 1 μm did trans-activate the LTR to a level comparable with that obtained with a transfected pCMV-Tat (data not shown).
The major result of trans-activation tests was the high activity of Tat Mal and Tat Eli, which correlates with the high virulence of these two HIV-1 isolates.
At 10 μm, the six Tat were showing levels of trans-activation so high that it was impossible to see differences between them because there was saturation.
Protein: DP03563 (UniProt P04611)
Region: residues 1	to 99
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
In aqueous buffer (Fig. 4 A), it can be deduced from the intensity of the negative 200 nm band that nonorganized structures are predominant (29)
Protein: DP03563 (UniProt P04611)
Region: residues 1	to 99
Annotation: regulatory region RNA binding (Molecular function)
Evidence: electrophoretic mobility shift assay evidence used in manual assertion
Supporting statements:
The K d values vary from approximately 50 nm for both Tat Eli and Tat Mal to about 140 nmfor Tat Oyi and Tat JR. 
The six synthetic Tat proteins can bind to TAR RNA (Fig.3) and can inhibit PKR (data not shown).
Protein: DP03563 (UniProt P04611)
Region: residues 1	to 99
Annotation: viral gene expression (Biological process)
Evidence: galactokinase reporter gene assay evidence used in manual assertion
Supporting statements:
In each case, Tat was added to the cell buffer, and therefore expression of β-gal up to the control means that the synthetic Tat was able to cross the cytoplasmic and nucleus membranes, bind TAR, and interact with cellular cofactors.
Tat Mal and Tat Eli show a level of trans-activation three to four times higher to that of Tat Bru.
The major result of trans-activation tests was the high activity of Tat Mal and Tat Eli, which correlates with the high virulence of these two HIV-1 isolates. Interestingly, the long C-terminal extremity of Tat Eli seems to improve the trans-activation compared with Tat Mal (Fig. 5).
Protein: DP03563 (UniProt P04611)
Region: residues 1	to 99
Annotation: viral gene expression (Biological process)
Evidence: luciferase reporter gene assay evidence used in manual assertion
Supporting statements:
Similar results were obtained with another transfection assay using luciferase as gene reporter, and Tat Mal and Tat Eli at 1 μm did trans-activate the LTR to a level comparable with that obtained with a transfected pCMV-Tat (data not shown).
The major result of trans-activation tests was the high activity of Tat Mal and Tat Eli, which correlates with the high virulence of these two HIV-1 isolates. Interestingly, the long C-terminal extremity of Tat Eli seems to improve the trans-activation compared with Tat Mal (Fig. 5).
At 0.2 μm, only Tat Eli was showing a level of trans-activation significantly higher than the base level. At 10 μm, the six Tat were showing levels of trans-activation so high that it was impossible to see differences between them because there was saturation.
Protein: DP03565 (UniProt P20893)
Region: residues 1	to 101
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
In aqueous buffer (Fig. 4 A), it can be deduced from the intensity of the negative 200 nm band that nonorganized structures are predominant (29).
Protein: DP03565 (UniProt P20893)
Region: residues 1	to 101
Annotation: regulatory region RNA binding (Molecular function)
Evidence: electrophoretic mobility shift assay evidence used in manual assertion
Supporting statements:
The K d values vary from approximately 50 nm for both Tat Eli and Tat Mal to about 140 nmfor Tat Oyi and Tat JR.
The six synthetic Tat proteins can bind to TAR RNA (Fig.3) and can inhibit PKR (data not shown).
Protein: DP03566 (UniProt P22363)
Region: residues 1	to 172
Annotation: disorder (Structural state)
Evidence: in vitro cleavage assay evidence used in manual assertion
Supporting statements:
The domain structure of this recombinant protein was probed by limited protease digestion using trypsin, endoprotease Lys-C and thermolysin. These proteases digest P to protease-resistant fragments that migrate on SDS-PAGE with apparent molecular masses of 15–16 kDa (Figure 3 A–C).
N-terminal sequencing of the fragment obtained after trypsin digestion showed that cleavage had occurred after R172. The apparent mass of the fragment from SDS-PAGE suggests that it contains residues 173–297.
Protein: DP03566 (UniProt P22363)
Region: residues 1	to 172
Annotation: phosphorylation display site (Disorder function)
Evidence: gel electrophoresis evidence used in manual assertion
Supporting statements:
We carried out systematic site-directed mutagenesis at those sites, altering S or T to A, expressed the mutant proteins in E. coli, and then purified and tested them for phosphorylation by RVPK and PKC. As shown in Fig. 6, altering S162 and S210 to A resulted in a drastic reduction in the ability of PKC to phosphorylate P protein (95%), whereas phosphorylation by RVPK was reduced by only 25%. These results suggest that PKC phosphorylation sites are probably S162, S210, and S271, which are presumably different from the RVPK sites which may be located at a different domain in the P protein.
Protein: DP03566 (UniProt P22363)
Region: residues 132	to 150
Annotation: molecular condensate scaffold activity (Molecular function)
Evidence: immunofluorescence confocal microscopy evidence used in manual assertion
Supporting statements:
Finally, we delineated more precisely the part of IDD2 domain which is required for phase separation. Deletion of residues 151–181 did not affect P ability to form NB-like structures (Fig. 6e). Therefore, only the amino-terminal part of IDD2 (residues 132–150) is required for this process. This was confirmed by the deletion of residues 139–151, which abolished spherical inclusions formation (Fig. 6e).
Protein: DP03567 (UniProt P0DOF3)
Region: residues 376	to 397
Annotation: disorder (Structural state)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
Two regions in N (NTD: 105 to 118 and CTD: 376 to 397) are presumably flexible, because they are absent in the structure (Fig. 1C and fig. S1).
Cross-references: PDB:2GTT
Protein: DP03567 (UniProt P0DOF3)
Region: residues 105	to 118
Annotation: disorder (Structural state)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
Two regions in N (NTD: 105 to 118 and CTD: 376 to 397) are presumably flexible, because they are absent in the structure (Fig. 1C and fig. S1).
Cross-references: PDB:2GTT
Protein: DP03568 (UniProt Q8JXF6)
Region: residues 376	to 397
Annotation: disorder (Structural state)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
Two regions in N (NTD: 105 to 118 and CTD: 376 to 397) are presumably flexible, because they are absent in the structure (Fig. 1C and fig. S1).
This IDR is 100% identical to the Rabies virus (strain ERA).
Cross-references: PDB:2GTT
Protein: DP03569 (UniProt F0TTD6)
Region: residues 159	to 252
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The NTD adopts the same nine-helix fold as present in previously determined crystal structures 12–14. The CTD, in contrast, is largely disordered, consistent with previous observations 24 and does not adopt detectable tertiary structure when pH is increased (Extended Data Fig. 4c).
Protein: DP03569 (UniProt F0TTD6)
Region: residues 159	to 252
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy evidence used in manual assertion
Supporting statements:
The PDB shows missing residues for this region.
Cross-references: PDB:6Z5J
Protein: DP03569 (UniProt F0TTD6)
Region: residues 187	to 217
Annotation: protein binding (Molecular function)
Evidence: cryogenic electron microscopy evidence used in manual assertion
Supporting statements:
The NTD-CTD interface appears to be stabilized by charge complementarity between the negatively charged membrane-distal surface of the NTD (residues Glu-8, Glu-23, Glu-29, Asp-30), and the positively charged interacting surface of the CTD (residues Lys-187, Arg-210, Arg-217), as well as by an inter-molecular salt bridge between Lys-21 and Glu-176 (Fig. 3c).
Cross-references: PDB:6Z5J
Protein: DP03569 (UniProt F0TTD6)
Region: residues 159	to 252
Annotation: order (Structural state)
Evidence: cryogenic electron microscopy evidence used in manual assertion
Supporting statements:
Polymerization is associated with extension of helix 9 and transition of the CTD from an unfolded to folded state, upon which it interacts with the NTD of the neighboring M1 molecule in the strand.
Cross-references: PDB:6Z5L
PDB:6Z5J
Protein: DP03569 (UniProt F0TTD6)
Region: residues 159	to 252
Annotation: disorder to order (Structural transition)
Evidence: cryogenic electron microscopy evidence used in manual assertion
Supporting statements:
Polymerization is associated with extension of helix 9 and transition of the CTD from an unfolded to folded state, upon which it interacts with the NTD of the neighboring M1 molecule in the strand.
Cross-references: PDB:6Z5L
PDB:6Z5J
Protein: DP03569 (UniProt F0TTD6)
Region: residues 159	to 252
Annotation: virion assembly (Biological process)
Evidence: cryogenic electron microscopy evidence used in manual assertion
Supporting statements:
 The NTD-CTD interface appears to be stabilized by charge complementarity between the negatively charged membrane-distal surface of the NTD (residues Glu-8, Glu-23, Glu-29, Asp-30), and the positively charged interacting surface of the CTD (residues Lys-187, Arg-210, Arg-217), as well as by an inter-molecular salt bridge between Lys-21 and Glu-176 (Fig. 3c).
This arrangement implies that virus assembly will be processive – binding of M1 into the filament induces conformational changes that create new interfaces promoting binding of the next monomer.
Cross-references: PDB:6Z5L
PDB:6Z5J
Protein: DP03569 (UniProt F0TTD6)
Region: residues 159	to 252
Annotation: self-assembly (Disorder function)
Evidence: cryogenic electron microscopy evidence used in manual assertion
Supporting statements:
 The NTD-CTD interface appears to be stabilized by charge complementarity between the negatively charged membrane-distal surface of the NTD (residues Glu-8, Glu-23, Glu-29, Asp-30), and the positively charged interacting surface of the CTD (residues Lys-187, Arg-210, Arg-217), as well as by an inter-molecular salt bridge between Lys-21 and Glu-176 (Fig. 3c).
This arrangement implies that virus assembly will be processive – binding of M1 into the filament induces conformational changes that create new interfaces promoting binding of the next monomer.
Cross-references: PDB:6Z5L
PDB:6Z5J
Protein: DP03571 (UniProt P03433)
Region: residues 372	to 397
Annotation: disorder (Structural state)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
Eighteen residues at the N terminus and a loop (residues 372–397)
between a3 and a4 are disordered, giving a total of 423 residues of PA
in the final model, beginning with Ile 257.
Cross-references: PDB:2ZNL
Protein: DP03572 (UniProt P03431)
Region: residues 16	to 81
Annotation: disorder (Structural state)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
Mass spectrometry confirmed that all 81 residues of the PB1-derived peptide are
present in the crystal, but most are invisible in the electron density.
Cross-references: PDB:2ZNL
Protein: DP03573 (UniProt A0A2Z5UJ33)
Region: residues 8	to 21
Annotation: disorder (Structural state)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
The nNLS sequence is located at the outer periphery of the nucleoprotein trimer where it is highly accessible to solvent (Fig. 3d). In addition, this region is disordered in electron density maps, and this flexibility should allow the nNLS to fit easily into the substrate recognition pocket on importin-a
Correct UniProt entry is Q1K9H2 [Influenza A virus (strain A/Wilson-Smith/1933 H1N1) (Influenza A virus (strain A/WS/1933 H1N1))]
Cross-references: PDB:2IQH
Protein: DP03573 (UniProt A0A2Z5UJ33)
Region: residues 73	to 91
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Residues preceding and succeeding disordered regions are marked and connected by dotted lines.
Missing residues on PDB entry 2IQH
Cross-references: PDB:2IQH
Protein: DP03573 (UniProt A0A2Z5UJ33)
Region: residues 203	to 212
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Residues preceding and succeeding disordered regions are marked and connected by dotted lines.
Missing residues on PDB entry 2IQH
Cross-references: PDB:2IQH
Protein: DP03573 (UniProt A0A2Z5UJ33)
Region: residues 8	to 21
Annotation: flexible N-terminal tail (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
In addition, this region is disordered in electron density maps, and this flexibility should allow the nNLS to fit easily into the substrate recognition pocket on importin-alpha.
Cross-references: PDB:2IQH
Protein: DP03575 (UniProt P03496)
Region: residues 204	to 230
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The N-terminal 73 amino-acid residues of NS1 form a symmetrical homodimeric RNA-binding domain (RBD) [23], [24], [25], [26], which is connected to the central effector domain (ED; residues 86-204) via an inter-domain linker [27]. The final ~25 residues of NS1 appear to be unstructured, and are termed the C-terminal flexible ‘tail’ (FT) ( Fig. 1A ) [28].
Neither the inter-domain linker nor the flexible ‘tail’ have been observed in crystal structures, and are therefore represented schematically.
Cross-references: PDB:3O9R
PDB:3O9Q
PDB:3O9S
PDB:3O9U
PDB:3O9T
Protein: DP03575 (UniProt P03496)
Region: residues 73	to 82
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Flexible linker connecting the RNA-binding domain (RBD) and the central effector domain (ED).
Cross-references: PDB:3L4Q
Protein: DP03575 (UniProt P03496)
Region: residues 73	to 82
Annotation: flexible linker (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Flexible linker connecting the RNA-binding domain (RBD) and the central effector domain (ED).
Protein: DP03577 (UniProt P15659)
Region: residues 197	to 257
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
Circular dichroism experiments revealed that the PA linker by itself is structurally disordered.
To investigate its structure in the absence of other viral components, the PA linker of the H1N1 A/WSN/33 (WSN) virus was expressed in Escherichia coli and purified to homogeneity. Its secondary structure was estimated using circular dichroism (CD) spectroscopy. The recorded spectra showed shape characteristics of a random coiled conformation with no evidence of stable secondary structures (Fig. 2). Dynamic light scattering analyses showed that the PA linker has a hydrodynamic radius of about 3 nm, suggesting that it exists as a monomer in solution. These data suggest that the PA linker mainly adopts a disordered structure when not associated with other polymerase components and that its conserved residues among influenza A, B, and C viruses are not the mark of intramolecular stable self-folding.
Protein: DP03577 (UniProt P15659)
Region: residues 210	to 226
Annotation: negative regulation of viral genome replication (Biological process)
Evidence: mutant phenotype evidence used in manual assertion
Supporting statements:
Temperature-Sensitive Mutants in the Influenza A Virus RNA Polymerase: Alterations in the PA Linker Reduce Nuclear Targeting of the PB1-PA Dimer and Result in Viral Attenuation
A large series of PA linker mutants exhibited a temperature-sensitive (ts) phenotype (reduced viral growth at 39.5°C versus 37°C/33°C), suggesting an alteration of folding kinetic parameters. The ts phenotype was associated with a reduced efficiency of replication/transcription of a pseudoviral reporter RNA in a minireplicon assay.
Overall, these data indicate that single substitutions in a small subdomain of the PA linker, mapping from positions 210 to 226, allow generation of mutants that display strong or less-pronounced ts phenotypes.
Protein: DP03577 (UniProt P15659)
Region: residues 210	to 226
Annotation: negative regulation of viral transcription (Biological process)
Evidence: mutant phenotype evidence used in manual assertion
Supporting statements:
Temperature-Sensitive Mutants in the Influenza A Virus RNA Polymerase: Alterations in the PA Linker Reduce Nuclear Targeting of the PB1-PA Dimer and Result in Viral Attenuation
A large series of PA linker mutants exhibited a temperature-sensitive (ts) phenotype (reduced viral growth at 39.5°C versus 37°C/33°C), suggesting an alteration of folding kinetic parameters. The ts phenotype was associated with a reduced efficiency of replication/transcription of a pseudoviral reporter RNA in a minireplicon assay.
Overall, these data indicate that single substitutions in a small subdomain of the PA linker, mapping from positions 210 to 226, allow generation of mutants that display strong or less-pronounced ts phenotypes.
Protein: DP03577 (UniProt P15659)
Region: residues 197	to 257
Annotation: flexible linker (Disorder function)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
We investigated the structure and function of the PA linker (residues 197 to 256), located between its N-terminal endonuclease domain and its C-terminal structured domain that binds PB1, the polymerase core. Circular dichroism experiments revealed that the PA linker by itself is structurally disordered.
To investigate its structure in the absence of other viral components, the PA linker of the H1N1 A/WSN/33 (WSN) virus was expressed in Escherichia coli and purified to homogeneity. Its secondary structure was estimated using circular dichroism (CD) spectroscopy. The recorded spectra showed shape characteristics of a random coiled conformation with no evidence of stable secondary structures (Fig. 2). Dynamic light scattering analyses showed that the PA linker has a hydrodynamic radius of about 3 nm, suggesting that it exists as a monomer in solution. These data suggest that the PA linker mainly adopts a disordered structure when not associated with other polymerase components and that its conserved residues among influenza A, B, and C viruses are not the mark of intramolecular stable self-folding.
Protein: DP03577 (UniProt P15659)
Region: residues 197	to 257
Annotation: RNA polymerase activity (Molecular function)
Evidence: mutant phenotype evidence used in manual assertion
Supporting statements:
We first observed that the wild-type polymerase activity was higher at 37°C than at 33°C (with an about 4-fold increase) and 39.5°C (2-fold). Compared to the wild type at a given temperature, all the polymerases reconstituted with a mutant PA had a reduced activity, a feature that was generally less pronounced at 33°C than at 37°C and 39.5°C (Fig. 6 and Table 2). Importantly, mutations T210P, K213P, D216P, F223P, and L226P, which induced a ts phenotype in the context of an infectious virus, also promoted a ts phenotype in the minireplicon assay, with a polymerase activity at 33°C ranging from 7 to 61% of the wild-type activity and less than 2% of the wild-type activity at 39.5°C (and even at 37°C).
Two additional points should be noted: (i) the drop of polymerase activity for the ts mutations was observed at 37°C (and 39.5°C), not only at 39.5°C, while the ts phenotype of the virus mutants was only identified at 39.5°C (and not at 37°C), suggesting that the minigenome test is more sensitive and/or does not strictly mimic the viral RNA polymerase activities in infected cells as previously observed (37); (ii) additional proline substitutions engineered at the extremities of the linker and at conserved positions between influenza A, B, and C viruses (E198, I201, Y232, and M249) were all deleterious for the polymerase activity and did not reveal additional mutations able to confer a ts phenotype in this assay.
The L214P virus mutant failed to be rescued, a hallmark in agreement with the absence of detectable RNA polymerase activity for PA L214P at all the tested temperatures in the minigenome assay (Fig. 6). However, PA L214P exhibited a less-pronounced defect than PA F223P (which allowed virus mutant recovery) in promoting PB1 translocation to the nucleus at 33°C (Fig. 7). These observations suggest that RNA synthesis activity per se may also be affected by the L214P mutation.