LiteFold/DisProt huggingface dataset:
Protein: DP00031 (UniProt P13255)
Region: residues 1	to 41
Annotation: self-inhibition (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
By comparing the open structure to the closed structure, mechanisms for auto-inhibition and for the forced release of the product AdoHcy have been revealed in the GNMT structure. The N-terminal section of the adjacent subunit occupies the AdoMet binding site and thus inhibits the methyltransfer reaction, whereas the same N-terminal section forces the departure of the potentially potent inhibitor AdoHcy from the active site and thus facilitates the methyltransfer reaction. Consequently GNMT is less active at a low level of AdoMet concentration, and is only weakly inhibited by AdoHcy.
Protein: DP00031 (UniProt P13255)
Region: residues 1	to 41
Annotation: order to disorder (Structural transition)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
The binding of AdoMet to the active site of subunit B enhances the movement of the N-terminal domain (residues 1-40) of subunit B.
This Arg175 modification study indicates that the binding of AdoMet opens the entrance of the active site and acetate binds to Arg175. Indeed, in the AdoHcy-R175K structure, the active site entrance is opened widely by binding the AdoHcy.
Authors are not considering the first Met residue, therefore the disordered region they are referring to is 1-41.
Cross-references: PDB:1D2C
PDB:1D2H
Protein: DP00032 (UniProt P56206)
Region: residues 85	to 170
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Our model for the insertion domain is at present incomplete due to crystalline disorder, but it contains conserved residues likely to interact with the acceptor arm of tRNAGlY.
However, electron density between residues 85 and 170 is weak and it has been possible to build only 50 of the intervening 85 residues in one monomer and 45 in the other, in most cases with Ala side chains only.
Cross-references: PDB:1ATI
Protein: DP00033 (UniProt P10912)
Region: residues 270	to 370
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
Analogously to the PRLR-ICD, two overlapping subdomains were constructed; GHR-ICDmp (Ser270-Ser370) and GHR-ICDmd (Val361–Pro620; Figure 1B). Far-UV CD and NMR spectroscopic analyses confirmed that both subdomains were intrinsically disordered with a low content of secondary structure (Supplementary Figures S5A–S5D) and no significant longrange intramolecular interactions as assessed by cross-titrations (Supplementary Figure S5E).
Protein: DP00033 (UniProt P10912)
Region: residues 270	to 370
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Analogously to the PRLR-ICD, two overlapping subdomains were constructed; GHR-ICDmp (Ser270-Ser370) and GHR-ICDmd (Val361–Pro620; Figure 1B). Far-UV CD and NMR spectroscopic analyses confirmed that both subdomains were intrinsically disordered with a low content of secondary structure (Supplementary Figures S5A–S5D) and no significant longrange intramolecular interactions as assessed by cross-titrations (Supplementary Figure S5E).
Protein: DP00033 (UniProt P10912)
Region: residues 361	to 620
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Analogously to the PRLR-ICD, two overlapping subdomains were constructed; GHR-ICDmp (Ser270-Ser370) and GHR-ICDmd (Val361–Pro620; Figure 1B). Far-UV CD and NMR spectroscopic analyses confirmed that both subdomains were intrinsically disordered with a low content of secondary structure (Supplementary Figures S5A–S5D) and no significant longrange intramolecular interactions as assessed by cross-titrations (Supplementary Figure S5E).
Protein: DP00033 (UniProt P10912)
Region: residues 361	to 620
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
Analogously to the PRLR-ICD, two overlapping subdomains were constructed; GHR-ICDmp (Ser270-Ser370) and GHR-ICDmd (Val361–Pro620; Figure 1B). Far-UV CD and NMR spectroscopic analyses confirmed that both subdomains were intrinsically disordered with a low content of secondary structure (Supplementary Figures S5A–S5D) and no significant longrange intramolecular interactions as assessed by cross-titrations (Supplementary Figure S5E).
Protein: DP00033 (UniProt P10912)
Region: residues 270	to 357
Annotation: lipid binding (Molecular function)
Evidence: heteronuclear single quantum coherence spectroscopy evidence used in manual assertion
Supporting statements:
We subsequently followed the same strategy as for the PRLR-ICD and chemical shift differences from 1 H-15N-HSQC spectra confirmed POPS specificity for GHRICDmp (Figures 3B and 3C). Pronounced chemical shift changes were observed in the membrane-proximal region of GHR-ICDmp upon POPC/POPS SUV binding (Lys287–Ser357) and signals from many of the N-terminal residues (Ser270–Lys287) disappeared, thereby identifying a LID1 comprising residues Ser270–Ser357 (Figure 3C). Again, to rule out artifacts from truncations, the lipid interaction was confirmed using full-length non-tagged GHRICD (GHR-ICDFL).
Protein: DP00034 (UniProt P03661)
Region: residues 86	to 107
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
In contrast, the Gly-rich linker segment from residue G69-T87 as well as adjacent residues N67-E68 and K88-P90 are not visible in either molecule A or B (Figure 1a).
The Gly-rich linker connecting D1 to D2 is not visible in the electron density map (see above).
The IDR characterized in the publication corresponds to region 86-107 of the amino acid sequence, since the natural precursor form of the protein contains a signal peptide (1-18) that is cleaved in the mature secreted protein.
Cross-references: PDB:2G3P
Protein: DP00034 (UniProt P03661)
Region: residues 86	to 107
Annotation: flexible linker (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
In contrast, the Gly-rich linker segment from residue G69-T87 as well as adjacent residues N67-E68 and K88-P90 are not visible in either molecule A or B (Figure 1a).
The Gly-rich linker connecting D1 to D2 is not visible in the electron density map (see above).
The IDR characterized in the publication corresponds to region 86-107 of the amino acid sequence, since the natural precursor form of the protein contains a signal peptide (1-18) that is cleaved in the mature secreted protein.
Cross-references: PDB:2G3P
Protein: DP00036 (UniProt P22121)
Region: residues 260	to 273
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Unstructured region inside the DNA-binding domain of HSF from K. lactis. The region has been identified from Fig.4, where secondary structure deduced from the NOESY data is indicated below the NOE data.
Protein: DP00036 (UniProt P22121)
Region: residues 1	to 195
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Yeast heat shock transcription factor N-terminal activation domains are unstructured as probed by heteronuclear NMR spectroscopy.
The remaining peaks in Figure 2B, all negative in intensity, can be attributed to the N-terminal activation domain. These additional peaks have poor shift dispersion in the proton dimension, as is the case for unstructured proteins. Integrating the volumes of the signals in the spectra could account for approximately 183 of the possible 192 residues; however, only 103 peaks were sufficiently resolved to calculate NOES. These NOE values (Fig. 4) are sorted by proton chemical shift because there are no sequence-specific assignments currently available for this domain. Negative values indicate that all of the residues in this region exhibit a high degree of rapid internal motion, typical for an unstructured protein.
Protein: DP00036 (UniProt P22121)
Region: residues 1	to 195
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
Far-UV CD spectroscopy, performed at pH 7.0, also indicate that the N-terminal activation domains of yeast HSF are unstructured. Figure 5A shows CD spectra for the DNA-binding domain, and for the N-terminal activation domain plus the DNA-binding domain, as well as the difference between the two. The difference spectrum is characteristic of a random coil. We also examined the possibility that the N-terminal activation do- main might behave differently when the DNA-binding domain is bound to a DNA-binding site (Fig. 5B). An examination of this CD difference spectrum indicates that binding of the DNA- binding domain to the DNA does not induce any structural changes in the N-terminal activation domain. Identical results were obtained for the K. lactis constructs (not shown).
Protein: DP00036 (UniProt P22121)
Region: residues 1	to 195
Annotation: molecular function activator activity (Molecular function)
Evidence: combinatorial experimental and author inference evidence contained in single publication used in manual assertion
Supporting statements:
Yeast heat shock transcription factor N-terminal activation domains are unstructured as probed by heteronuclear NMR spectroscopy.
Using the DNA-binding domain as a structural reference, we show that the protein backbone of the N-terminal activation domain undergoes rapid, large-amplitude motions and is therefore unstructured. Difference CD data also show that the N-terminal activation domain remains random-coil, even in the presence of DNA.
In addition, we used two-dimensional heteronuclear 15N{1H} NOE NMR and measurements of 15N relaxation parameters to show that the N-terminal activation domains from both yeast strains have a high degree of flexibility, which is consistent with an unstructured state in solution. The results are particularly compelling because they offer the first positive evidence for a dynamically disordered transcriptional activation domain.
Protein: DP00040 (UniProt P17096)
Region: residues 1	to 107
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
In the absence of DNA, the NMR spectrum of HMG-1(2/3) is indicative of a random coil. Upon binding, the two DBDs that contact the DNA become ordered and adopt a well defined conformation in the minor groove.
Protein: DP00040 (UniProt P17096)
Region: residues 51	to 75
Annotation: DNA binding (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
In the absence of DNA, the NMR spectrum of HMG-1(2/3) is indicative of a random coil. Upon binding, the two DBDs that contact the DNA become ordered and adopt a well defined conformation in the minor groove.
The stoichiometry of binding was established by a series of titra-tion experiments using 15N/13C[Gly 11 ]-HMG-1(2/3) and 15N/13C-[Gly 37]-HMG-1(2/3) in which a single glycine in DBD2 and DBD3 respectively was isotopically labelled (Fig. 2a). HMG-1(2/3) binds to the PRDII dodecamer with DBD2 on the slow side of intermediate exchange; at ratios of DNA to protein less than 1:1, the cross-peak of Gly 11 in the 1H-15N correlation spectrum is broadened out (note this may also be due to non-specific interactions resulting in the formation of higher order structures since some precipitation is observed at ratios of DNA to protein below 1: 1 which completely dears up upon further addition of DNA); at a 1: 1 ratio the cross peak is located at the position of the bound form and does not shift upon further addition of DNA, although it does sharpen up slightly. 
The DNA in the DBD2 and DBD3 complexes is essentially B-type (Figs 4, 5).
DNA-binding motifs DBD2 of HMGA1
Cross-references: PDB:2EZD
PDB:2EZE
Protein: DP00040 (UniProt P17096)
Region: residues 51	to 75
Annotation: disorder to order (Structural transition)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
In the absence of DNA, the NMR spectrum of HMG-1(2/3) is indicative of a random coil. Upon binding, the two DBDs that contact the DNA become ordered and adopt a well defined conformation in the minor groove.
The stoichiometry of binding was established by a series of titra-tion experiments using 15N/13C[Gly 11 ]-HMG-1(2/3) and 15N/13C-[Gly 37]-HMG-1(2/3) in which a single glycine in DBD2 and DBD3 respectively was isotopically labelled (Fig. 2a). HMG-1(2/3) binds to the PRDII dodecamer with DBD2 on the slow side of intermediate exchange; at ratios of DNA to protein less than 1:1, the cross-peak of Gly 11 in the 1H-15N correlation spectrum is broadened out (note this may also be due to non-specific interactions resulting in the formation of higher order structures since some precipitation is observed at ratios of DNA to protein below 1: 1 which completely dears up upon further addition of DNA); at a 1: 1 ratio the cross peak is located at the position of the bound form and does not shift upon further addition of DNA, although it does sharpen up slightly. 
The DNA in the DBD2 and DBD3 complexes is essentially B-type (Figs 4, 5).
DNA-binding motifs DBD2 of HMGA1
Cross-references: PDB:2EZD
PDB:2EZE
Protein: DP00040 (UniProt P17096)
Region: residues 80	to 89
Annotation: disorder to order (Structural transition)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
In the absence of DNA, the NMR spectrum of HMG-1(2/3) is indicative of a random coil. Upon binding, the two DBDs that contact the DNA become ordered and adopt a well defined conformation in the minor groove.
In contrast, Gly 37 of DBD3 is in fast exchange and its cross peak in the 1H-15N correlation spectrum only begins to shift from its position in the free state at ratios of DNA to protein greater than about 0.8:1, reaching the position of the bound form at a ratio of2:l. Thus, under our experimental conditions, one molecule ofHMG-1(2/3) binds two molecules of the PRDII dodecamer, the equilibrium association constant for the interaction of DBD3 with the PRDII dodecamer is -1.0(±0.5)xl05 M-1, and the affinity of DBD2 for the PRDII dodecamer is about one to two orders of magnitude greater than that ofDBD3.
The DNA in the DBD2 and DBD3 complexes is essentially B-type (Figs 4, 5).
DNA-binding motifs DBD3 of HMGA1
Cross-references: PDB:2EZG
PDB:2EZF
Protein: DP00040 (UniProt P17096)
Region: residues 80	to 89
Annotation: DNA binding (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
In the absence of DNA, the NMR spectrum of HMG-1(2/3) is indicative of a random coil. Upon binding, the two DBDs that contact the DNA become ordered and adopt a well defined conformation in the minor groove.
In contrast, Gly 37 of DBD3 is in fast exchange and its cross peak in the 1H-15N correlation spectrum only begins to shift from its position in the free state at ratios of DNA to protein greater than about 0.8:1, reaching the position of the bound form at a ratio of2:l. Thus, under our experimental conditions, one molecule ofHMG-1(2/3) binds two molecules of the PRDII dodecamer, the equilibrium association constant for the interaction of DBD3 with the PRDII dodecamer is -1.0(±0.5)xl05 M-1, and the affinity of DBD2 for the PRDII dodecamer is about one to two orders of magnitude greater than that ofDBD3.
The DNA in the DBD2 and DBD3 complexes is essentially B-type (Figs 4, 5).
DNA-binding motifs DBD3 of HMGA1
Cross-references: PDB:2EZG
PDB:2EZF
Protein: DP00040 (UniProt P17096)
Region: residues 80	to 89
Annotation: DNA binding, bending (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
Bending of the DNA is probably due to the presence of the AT-hook, which distorts the minor groove.
Protein: DP00040 (UniProt P17096)
Region: residues 1	to 107
Annotation: disorder (Structural state)
Evidence: circular dichroism evidence used in manual assertion
Supporting statements:
Circular dichroism spectrum of the HMGA1a (a.k.a. HMG-I) protein is essentially unstructured while free in solution.
Protein: DP00040 (UniProt P17096)
Region: residues 51	to 55
Annotation: phosphorylation display site (Disorder function)
Evidence: fluorescence polarization evidence used in manual assertion
Supporting statements:
A threonine residue at the beginning of each DNA-binding domain of HMG-I (residue numbers 21, 53, and 78) is conserved among mammalian species and proposed to help stabilize the A.T-hook DNA-binding motif. Phosphorylation of threonines number 53 and 78 of human HMG-I(Y) both in vivo and in vitro leads to a 20 fold reduction in the proteins DNA binding affinity.
Replacement of these threonines did not affect the equilibrium binding of these proteins to DNA as compared with wild-type HMG-I and HMG-Y. Molecular modelling of analogous peptides supported this finding. We conclude that these threonines are not directly important for A.T-hook DNA-binding and are conserved phosphorylation sites for down regulation of DNA binding by the A.T-hook motif in the HMG-I(Y) proteins.
Phosphorylated Thr53 and flanking regions.
Protein: DP00040 (UniProt P17096)
Region: residues 76	to 80
Annotation: phosphorylation display site (Disorder function)
Evidence: fluorescence polarization evidence used in manual assertion
Supporting statements:
A threonine residue at the beginning of each DNA-binding domain of HMG-I (residue numbers 21, 53, and 78) is conserved among mammalian species and proposed to help stabilize the A.T-hook DNA-binding motif. Phosphorylation of threonines number 53 and 78 of human HMG-I(Y) both in vivo and in vitro leads to a 20 fold reduction in the proteins DNA binding affinity.
Replacement of these threonines did not affect the equilibrium binding of these proteins to DNA as compared with wild-type HMG-I and HMG-Y. Molecular modelling of analogous peptides supported this finding. We conclude that these threonines are not directly important for A.T-hook DNA-binding and are conserved phosphorylation sites for down regulation of DNA binding by the A.T-hook motif in the HMG-I(Y) proteins.
Phosphorylated Thr78 and flanking regions.
Protein: DP00040 (UniProt P17096)
Region: residues 100	to 105
Annotation: phosphorylation display site (Disorder function)
Evidence: enzymatic activity assay evidence used in manual assertion
Supporting statements:
Sequence analysis of the native peptide (90-107) after treatment, which specifically converts phosphoserine residues to S-ethylcysteine, revealed that 70-80% of serine residues 102 and 103 were phosphorylated in vivo. Both residues were fully phosphorylated in vitro by incubation with casein kinase II.
Protein: DP00040 (UniProt P17096)
Region: residues 6	to 11
Annotation: ADP-ribosylation display site (Disorder function)
Evidence: protein mass spectrometry evidence used in manual assertion
Supporting statements:
High-resolution ETD analysis confirmed ADPr on S499, S507, and S519 in PARP-1, and it revealed five targets of S-ADPr as follows: HMGA1 (S8 and S9), HMGB1 (S181), HMGN1 (S7), NPM1 (S207), and TMA7 (S61) (Figures 3A–3C, S3A, and S3B).
ADP-ribosylation of Ser8 and Ser9 of HMGA1 depends on HPF1.
Protein: DP00040 (UniProt P17096)
Region: residues 1	to 107
Annotation: molecular adaptor activity (Molecular function)
Evidence: combinatorial experimental and author inference evidence contained in single publication used in manual assertion
Supporting statements:
Reversible transitions between disordered and ordered configurations of the HMGA proteins, mediated by labile secondary biochemical modifications (Fig. 2), are likely to provide the necessary molecular underpinning for regulating the formation of functional HMGA complexes in cells and thereby controlling the biological activity of these proteins in vivo.
Protein: DP00040 (UniProt P17096)
Region: residues 9	to 75
Annotation: DNA binding (Molecular function)
Evidence: immunodetection assay evidence used in manual assertion
Supporting statements:
A derivative of HMG I lacking amino acids 91 to 108, the acidic C-terminal domain, was also capable of reconstituting integration activity (Fig. ​(Fig.3B,3B, lane 4). Derivatives containing amino acids 9 to 75 or 50 to 91, either A/T hooks 1 plus 2 or 2 plus 3, also reconstituted activity (Fig. ​(Fig.3B,3B, lanes 6, 8, and 9). The 50–91 protein displayed the highest specific activity for reconstitution, retaining activity at 0.2 μg per reaction.
We also demonstrated that the HIV-1 long terminal repeats (LTRs) contain multiple DNA binding sites for HMG I(Y). Tests in vitro revealed that binding of HMG I(Y) apposed LTR DNAs in a manner that promoted intermolecular ligation of dilute DNA solutions. As with assays of PIC reconstitution, these assays of DNA condensation required multiple DNA binding domains in each HMG I(Y) monomer. Taken together, these studies strengthen the idea that HMG I(Y) acts as an architectural cofactor for retroviral cDNA integration complexes and suggest a model for its role.
HMGA1 fragment including AT-hook 1 and 2.
Protein: DP00040 (UniProt P17096)
Region: residues 50	to 91
Annotation: DNA binding (Molecular function)
Evidence: immunodetection assay evidence used in manual assertion
Supporting statements:
A derivative of HMG I lacking amino acids 91 to 108, the acidic C-terminal domain, was also capable of reconstituting integration activity (Fig. ​(Fig.3B,3B, lane 4). Derivatives containing amino acids 9 to 75 or 50 to 91, either A/T hooks 1 plus 2 or 2 plus 3, also reconstituted activity (Fig. ​(Fig.3B,3B, lanes 6, 8, and 9). The 50–91 protein displayed the highest specific activity for reconstitution, retaining activity at 0.2 μg per reaction.
We also demonstrated that the HIV-1 long terminal repeats (LTRs) contain multiple DNA binding sites for HMG I(Y). Tests in vitro revealed that binding of HMG I(Y) apposed LTR DNAs in a manner that promoted intermolecular ligation of dilute DNA solutions. As with assays of PIC reconstitution, these assays of DNA condensation required multiple DNA binding domains in each HMG I(Y) monomer. Taken together, these studies strengthen the idea that HMG I(Y) acts as an architectural cofactor for retroviral cDNA integration complexes and suggest a model for its role.
HMGA1 fragment including AT-hook 2 and 3.