LiteFold/DisProt huggingface dataset:
Protein: DP02925 (UniProt P0DTD1)
Region: residues 163	to 167
Annotation: copper ion binding (Molecular function)
Evidence: fluorescence resonance energy transfer evidence used in manual assertion
Supporting statements:
Nsp1-CT W161 fluorescence is sensitive to low concentrations of Cu(II). At 30 μM peptide concentration, addition of 1 mol equiv of aquo Cu(II) leads to an ∼25% reduction in W161 fluorescence intensity. Cu(II) also produces a systematic reduction in the effective W161 fluorescence lifetime. Treating the reduction in ⟨τ⟩ with a single Cu-binding-site model leads to a dissociation constant of 9.7 μM (pH 6.5) (Figure 3). *W161 fluorescence in an Nsp1 variant in which H165 is replaced by alanine (Nsp1-CT(H165A)) is only weakly quenched by Cu(II) with an apparent dissociation constant of 106 μM (Figure S2). This result is consistent with the relative Cu(II) binding constants of imidazole (104.02 M–1) and a carboxylate (acetate, 101.82 M–1). (16) Importantly, the *W161 quenching data clearly implicate H165 as the site of Cu(II) coordination to Nsp1-CT.
Protein: DP02925 (UniProt P0DTD1)
Region: residues 163	to 167
Annotation: copper ion binding (Molecular function)
Evidence: mutant phenotype evidence used in manual assertion
Supporting statements:
Nsp1-CT W161 fluorescence is sensitive to low concentrations of Cu(II). At 30 μM peptide concentration, addition of 1 mol equiv of aquo Cu(II) leads to an ∼25% reduction in W161 fluorescence intensity. Cu(II) also produces a systematic reduction in the effective W161 fluorescence lifetime. Treating the reduction in ⟨τ⟩ with a single Cu-binding-site model leads to a dissociation constant of 9.7 μM (pH 6.5) (Figure 3). *W161 fluorescence in an Nsp1 variant in which H165 is replaced by alanine (Nsp1-CT(H165A)) is only weakly quenched by Cu(II) with an apparent dissociation constant of 106 μM (Figure S2). This result is consistent with the relative Cu(II) binding constants of imidazole (104.02 M–1) and a carboxylate (acetate, 101.82 M–1). (16) Importantly, the *W161 quenching data clearly implicate H165 as the site of Cu(II) coordination to Nsp1-CT.
Protein: DP02926 (UniProt A8BB85)
Region: residues 135	to 160
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
In addition, no electron density is associated with the following surface residues: 18–19, 135–160 and 272–273 in molecule A, 138–152, 244–245 and 271–272 in molecule B, 138–161 and 247–250 in molecule C, and 140–152, 243–249 and 271–272 in molecule D.
Cross-references: PDB:3KZF
Protein: DP02927 (UniProt Q26997)
Region: residues 116	to 126
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
In the structure of the enzyme bound to its product, a long flexible loop (residues 115-126) is located away from the active site.
There is no density for residues 116-126 in subunits B, C and D, indicating that these residues are disordered.
Cross-references: PDB:1DBR
Protein: DP02928 (UniProt A0A220GHA5)
Region: residues 1	to 22
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Here, we report the solution structure of AcrIIA5, which features a novel α/β fold connected to an N-terminal intrinsically disordered region (IDR).
Here, we show that AcrIIA5 adopts a novel α/β fold preceded by an intrinsically disordered region (IDR).
AcrIIA5 comprises seven β-strands and two α-helices, preceded by an extended N-terminal disordered region (Figure 1B).
We note that the N-terminal 22 residues of AcrIIA5 display largely disordered backbone conformations (Figure 2A).
In addition, the N-terminal tail region exhibited a narrow dispersion of backbone chemical shifts, which is typically observed in unfolded proteins (Supplementary Figure S1B).
Heteronuclear NOEs are sensitive to fast internal dynamics, and thus can discriminate flexible loop and tail regions from rigid secondary structures. Residues in the folded region of AcrIIA5 showed large 1H–15N heteronuclear NOE values (>0.8), whereas the N-terminal disordered region exhibited significantly reduced NOE values (<0.6), a signature of conformational flexibility (Figure 2B).
AcrIIA5 is unique among known Acr proteins in that it contains a long unstructured tail region at the N-terminus. The 22-residue tail also possesses an amino acid composition biased toward disorder, including three lysine, four arginine, and four serine residues
Cross-references: PDB:6LKF
BMRB:50185
Protein: DP02928 (UniProt A0A220GHA5)
Region: residues 1	to 22
Annotation: molecular function inhibitor activity (Molecular function)
Evidence: deletion mutation phenotypic evidence used in manual assertion
Supporting statements:
Remarkably, truncation of the N-terminal IDR abrogates the inhibitory activity against Cas9, revealing that the IDR is essential for Cas9 inhibition by AcrIIA5.
N-terminal disorder is essential for Cas9 inhibition by AcrIIA5
We employed the N-terminal truncated AcrIIA5Δ20 to examine whether the IDR was dispensable for Cas9 inhibition by AcrIIA5. Remarkably, AcrIIA5Δ20 completely lost its ability to inhibit Cas9, revealing that the N-terminal disordered region is essential for Acr activity (Figure 3C).
Truncation of the first 5 N-terminal residues (AcrIIA5Δ5) showed a ∼40% reduction of Cas9 inhibition, and further truncations abolished the Acr activity (Figure 3E). Thus, the length of the IDR was important for Cas9 inhibition of AcrIIA5, such that an IDR length of >20 residues was required to maintain the maximal inhibitory activity against Cas9.
The IDR peptide alone (residues 1–20) failed to show any inhibitory activity against Cas9, indicating that the IDR functions in Cas9 inhibition only in concert with the folded region of AcrIIA5 (Figure 3G).
Taken together, the Cas9 inhibition of AcrIIA5 requires an IDR sequence that is covalently linked to the structured region.
Specifically, the length of the IDR provides a scaffold for association between AcrIIA5 and Cas9–sgRNA, while the positive charges of the IDR serve as a regulatory switch that hinders Cas9 function upon binding.
Protein: DP02928 (UniProt A0A220GHA5)
Region: residues 1	to 22
Annotation: RNA binding (Molecular function)
Evidence: electrophoretic mobility shift assay evidence used in manual assertion
Supporting statements:
The IDR mediates direct interaction between AcrIIA5 and Cas9–sgRNA
Taken together, AcrIIA5 selectively binds to sgRNA-loaded Cas9 and inhibits the nuclease activity without competing with target DNA binding, which is unique among Cas9 inhibitors.
The size and sequence of the IDR modulate AcrIIA5 binding to Cas9 and inhibition of the nuclease activity.
Protein: DP02929 (UniProt P0A2N1)
Region: residues 1	to 26
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The final model of the native structure contains residues 28–241 and misses residues 1–27, 66–67, 95, and 218–225 due to the lack of electron density. Two regions (residues 1–26 and 95–98) are disordered in the structure of the SpvC/phosphopeptide complex.
The N-terminal 26 residues are disordered in both the native SpvC structure and its complex with the peptide substrate (Figures 2A and 2B).
Cross-references: PDB:2Q8Y
PDB:2P1W
Protein: DP02930 (UniProt Q9Y6I3)
Region: residues 1	to 18
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Mapping of the changes in the chemical shift onto the three-dimensional structure showed that the most perturbed residues are localized at three sites: the NH2-terminal unstructured region (site 1), the solvent-exposed surface of the first helix (site 2), and the region around loop 1 (loop connecting helices 1 and 2) and loop 3 (loop connecting helices 3 and 4) and helix 4 (site 3) (Fig. 2, A and B).
Protein: DP02930 (UniProt Q9Y6I3)
Region: residues 1	to 18
Annotation: small molecule binding (Molecular function)
Evidence: co-sedimentation assay evidence used in manual assertion
Supporting statements:
Results suggest that site 1, the NH2-terminal unstructured region, was necessary for binding and adopted a specific conformation upon binding to PtdIns(4,5)P2.
Many residues in site 1 showed large chemical shift changes, suggesting a large structural change upon phosphoinositide binding (Fig. 2A). Deletion of the entire site 1 region (NH2-terminal, 18 residues) resulted in a complete loss of PtdIns(4,5)P2binding (Fig. 2F).
Protein: DP02930 (UniProt Q9Y6I3)
Region: residues 1	to 18
Annotation: disorder to order (Structural transition)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Results suggest that site 1, the NH2-terminal unstructured region, was necessary for binding and adopted a specific conformation upon binding to PtdIns(4,5)P2.
Many residues in site 1 showed large chemical shift changes, suggesting a large structural change upon phosphoinositide binding (Fig. 2A). Deletion of the entire site 1 region (NH2-terminal, 18 residues) resulted in a complete loss of PtdIns(4,5)P2binding (Fig. 2F).
Protein: DP02930 (UniProt Q9Y6I3)
Region: residues 1	to 18
Annotation: molecular sequestering activity (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Results suggest that site 1, the NH2-terminal unstructured region, was necessary for binding and adopted a specific conformation upon binding to PtdIns(4,5)P2.
Many residues in site 1 showed large chemical shift changes, suggesting a large structural change upon phosphoinositide binding (Fig. 2A). Deletion of the entire site 1 region (NH2-terminal, 18 residues) resulted in a complete loss of PtdIns(4,5)P2binding (Fig. 2F).
Protein: DP02930 (UniProt Q9Y6I3)
Region: residues 1	to 18
Annotation: molecular sequestering activity (Molecular function)
Evidence: co-sedimentation assay evidence used in manual assertion
Supporting statements:
Results suggest that site 1, the NH2-terminal unstructured region, was necessary for binding and adopted a specific conformation upon binding to PtdIns(4,5)P2.
Many residues in site 1 showed large chemical shift changes, suggesting a large structural change upon phosphoinositide binding (Fig. 2A). Deletion of the entire site 1 region (NH2-terminal, 18 residues) resulted in a complete loss of PtdIns(4,5)P2binding (Fig. 2F).
Protein: DP02931 (UniProt Q9RQJ2)
Region: residues 464	to 484
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The crystallised tPPADWT and tPPADC351A constructs include residues aa464–484, with no visible electron density.
Cross-references: PDB:5AK7
PDB:5AK8
Protein: DP02931 (UniProt Q9RQJ2)
Region: residues 464	to 484
Annotation: flexible linker (Disorder function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
The crystallised tPPADWT and tPPADC351A constructs include residues aa464–484, with no visible electron density. This region represents a flexible linker connecting the IgLF and CTD in the full-length polypeptide, and its flexibility likely caused disorder in the crystal.
Protein: DP02933 (UniProt Q9KRE7)
Region: residues 1	to 21
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Whereas the construct used for crystallization contained the entire 280 amino acid sequence, the first 22 amino acids at the N-terminus and the last three at the C-terminus are disordered in the crystal.
Cross-references: PDB:3KLZ
PDB:3KLY
Protein: DP02934 (UniProt Q8I2X3)
Region: residues 122	to 136
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Two loops comprising residues 122 to 136 and 161 to 169, were disordered and therefore not included in the structure.
Cross-references: PDB:3TGH
Protein: DP02937 (UniProt A0A0H3MCR9)
Region: residues 1	to 13
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
In addition, potentially owing to the use of limited proteolysis in order to crystallize CT548, residues at both the amino-terminus (Met1–Asn13) and carboxy-terminus (Lys181–Val183) could not be modeled due to poor electron density.
Cross-references: PDB:4MLK
Protein: DP02939 (UniProt O61130)
Region: residues 297	to 334
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Several breaks occur in the main-chain tracing of all three domains as a result of absent or poorly defined electron density; these regions correspond to 15% of the polypeptide chain (fig. S2). Of particular note, no electron density was present for the 40-residue segment 295 to 334 in domain II, showing that this region is disordered or mobile. We refer to this region as the domain II loop.
The defined region relies on examining the missing coordinates in both reported X-ray structures attached to the publication (1w8k and 1w81), therefore the exact boundaries might be slightly different from the ones reported in the paper.
Cross-references: PDB:1W8K
PDB:1W81
Protein: DP02939 (UniProt O61130)
Region: residues 205	to 215
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Several breaks occur in the main-chain tracing of all three domains as a result of absent or poorly defined electron density; these regions correspond to 15% of the polypeptide chain (fig. S2). Of particular note, no electron density was present for the 40-residue segment 295 to 334 in domain II, showing that this region is disordered or mobile. We refer to this region as the domain II loop.
The region is defined based on missing coordinates in the two structures reported in the publication (1w8k and 1w81).
Cross-references: PDB:1W8K
PDB:1W81
Protein: DP02939 (UniProt O61130)
Region: residues 403	to 412
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Several breaks occur in the main-chain tracing of all three domains as a result of absent or poorly defined electron density; these regions correspond to 15% of the polypeptide chain (fig. S2). Of particular note, no electron density was present for the 40-residue segment 295 to 334 in domain II, showing that this region is disordered or mobile. We refer to this region as the domain II loop.
The region is defined based on missing coordinates in the two structures reported in the publication (1w8k and 1w81).
Cross-references: PDB:1W8K
PDB:1W81
Protein: DP02940 (UniProt P07749)
Region: residues 1	to 17
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The first 17 residues from the N terminus appear unstructured and solvent-exposed.
The unstructured N-terminal region of FCaBP suggests that its covalently attached myristoyl group at the N terminus may be solvent-exposed, in contrast to the highly sequestered myristoyl group seen in recoverin and GCAP1. NMR analysis demonstrates that the myristoyl group attached to FCaBP is indeed solvent-exposed in both the Ca2+-free and Ca2+-bound states, and myristoylation has no effect on protein structure and folding stability.
In each crystal form, the first 17 residues from the N terminus appear disordered.
High temperature factors for the N-terminal residues suggest they may be dynamically disordered.
Cross-references: PDB:3CS1
Protein: DP02940 (UniProt P07749)
Region: residues 1	to 17
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
NMR relaxation studies and heteronuclear 15N nuclear Overhauser effect (NOE) analysis on FCaBP also confirms that the first 17 N-terminal residues are indeed unstructured (data not shown) and the N-terminal myristoyl group is solvent-exposed (see below). 
The absence of detectable electron density from the first 17 residues of FCaBP suggested that the N-terminal region and myristoyl group may be structurally disordered.
Protein: DP02941 (UniProt P50490)
Region: residues 513	to 546
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The region defined here is based on the missing residues in the PDB structure 2j5l, with removing the transmembrane and the cytoplasmic regions based on UniProt entry P50490. 
Although the complete recombinant PvAMA1 ectoplasmic region (residues 43–487) and domains II and III of PfAMA1 (residues 303 to 544) were complexed with Fab F8.12.19 in the protein preparations used for crystallisation, only a small but contiguous segment of domain III from these two homologues could be identified in the electron density: the 34-residue segment from Ile421 to Lys454 in PvAMA1 and the equivalent 34-residue segment from Ile479 to Arg512 in PfAMA1 (Figure 4). This part of the antigen could be identified readily in the electron density by the cystine knot formed with Cys432-Cys449 and Cys434-Cys451 in PvAMA1 and Cys490-Cys507 and Cys492-Cys509 in PfAMA1. Additional electron density, observed in the final difference maps of both PvAMA1 and PfAMA1, did not coincide with the complete, superimposed PvAMA1 structure (PDB entry 1W8K) (Figure 5). This region is connected to modelled part of the antigen via the Cys388-Cys444 bridge in PvAMA1 (443Cys-502Cys in PfAMA1) but the electron density was too disordered to propose an unambiguous interpretation. No other region of significant electron density occurred in the maps. 
Cross-references: PDB:2J5L
Protein: DP02941 (UniProt P50490)
Region: residues 439	to 479
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Although the complete recombinant PvAMA1 ectoplasmic region (residues 43–487) and domains II and III of PfAMA1 (residues 303 to 544) were complexed with Fab F8.12.19 in the protein preparations used for crystallisation, only a small but contiguous segment of domain III from these two homologues could be identified in the electron density: the 34-residue segment from Ile421 to Lys454 in PvAMA1 and the equivalent 34-residue segment from Ile479 to Arg512 in PfAMA1 (Figure 4). This part of the antigen could be identified readily in the electron density by the cystine knot formed with Cys432-Cys449 and Cys434-Cys451 in PvAMA1 and Cys490-Cys507 and Cys492-Cys509 in PfAMA1. Additional electron density, observed in the final difference maps of both PvAMA1 and PfAMA1, did not coincide with the complete, superimposed PvAMA1 structure (PDB entry 1W8K) (Figure 5). This region is connected to modelled part of the antigen via the Cys388-Cys444 bridge in PvAMA1 (443Cys-502Cys in PfAMA1) but the electron density was too disordered to propose an unambiguous interpretation. No other region of significant electron density occurred in the maps.
The region defined here is based on the missing residues in the PDB structure 2j5l, taking into consideration the ordered domain from the same protein described in PDB structure 4r1a.
Cross-references: PDB:2j5l
PDB:4r1a
Protein: DP02943 (UniProt P63101)
Region: residues 234	to 245
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
1H-NMR spectroscopy revealed the presence of a flexible and unstructured C-terminal extension, 12 amino acids in length, which protrudes from the domain core of 14-3-3ζ and is similar in structure and length to the C-terminal extension of mammalian sHsps. The extension stabilizes 14-3-3ζ
It has been proposed that the C-terminus of 14-3-3ζ (Asp231–Asn245) adopts a poorly ordered conformation
Taken together these results indicated that the strongest cross-peaks in the two-dimensional NMR spectra of full-length 14-3-3ζ were attributable to the 12 amino acid residues at the extreme C-terminus of the 14-3-3ζ dimer (i.e. from Gly234 to Asn245), with no cross-peaks being observed for residues preceding Gly234
thus 14-3-3ζ has a flexible C-terminal extension encompassing its last 12 amino acids that is directly comparable with the C-terminal extension of mammalian sHsps in terms of its polar nature and conformational flexibility
Consistent with folding prediction algorithms, the NMR data indicate that the last 12 C-terminal amino acids of 14-3-3ζ (Gly234–Asp245) are solvent-exposed and exhibit flexibility that is independent of the domain core of the protein, while adopting no preferred secondary structure
Therefore it is concluded that 14-3-3ζ, and by analogy all other 14-3-3 proteins, have a flexible C-terminal extension.
Protein: DP02945 (UniProt Q96RD7)
Region: residues 163	to 190
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
We were able to model most of PANX1 except for the linker connecting the intracellular helices IH1 and IH2 (residues 163–190), and the CTT (residues 374–426).
The disordered IH1–IH2 linker (residues 163–190) and the CTT (residues after 373) are indicated by dashed lines
Cross-references: PDB:6WBF
Protein: DP02945 (UniProt Q96RD7)
Region: residues 163	to 190
Annotation: flexible linker (Disorder function)
Evidence: cryogenic electron microscopy evidence used in manual assertion
Supporting statements:
We were able to model most of PANX1 except for the linker connecting the intracellular helices IH1 and IH2 (residues 163–190), and the CTT (residues 374–426).
The disordered IH1–IH2 linker (residues 163–190) and the CTT (residues after 373) are indicated by dashed lines
Cross-references: PDB:6WBF
Protein: DP02945 (UniProt Q96RD7)
Region: residues 374	to 426
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
We were able to model most of PANX1 except for the linker connecting the intracellular helices IH1 and IH2 (residues 163–190), and the CTT (residues 374–426).
The disordered IH1–IH2 linker (residues 163–190) and the CTT (residues after 373) are indicated by dashed lines