LiteFold/DisProt huggingface dataset:
Protein: DP04129 (UniProt P42858)
Region: residues 1179	to 1199
Annotation: phosphorylation display site (Disorder function)
Evidence: liquid chromatography coupled with tandem mass spectrometry evidence used in manual assertion
Supporting statements:
Besides the polyQ tract, a large portion of N-HEAT domain (aa 409–666 in Q23-HTT) in the high-resolution cryo-EM structure is unstructured in addition to several small regions in other domains.
Interestingly, many residues in the large unstructured region in N-HEAT domain are shown to be phosphorylated, and these modifications seem to modify HTT function.
Several HTT phosphorylation sites were identified by MS and are listed along the length of the HTT amino acid sequence.
Phosphosites on Figure 6A in the IDR streching between aa. 1162-1226 within the N-HEAT domain: pS1181 and pS1201. With UniProt numbering these correspond to pS1179 and pS1199.
Protein: DP04129 (UniProt P42858)
Region: residues 1162	to 1226
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Besides the polyQ tract, a large portion of N-HEAT domain (aa 409–666 in Q23-HTT) in the high-resolution cryo-EM structure is unstructured in addition to several small regions in other domains.
One of these additional smaller IDRs streches between aa. 1162-1226 within the N-HEAT domain.
Cross-references: EMDB:EMD-4937
PDB:6RMH
Protein: DP04129 (UniProt P42858)
Region: residues 1	to 94
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Besides the polyQ tract, a large portion of N-HEAT domain (aa 409–666 in Q23-HTT) in the high-resolution cryo-EM structure is unstructured in addition to several small regions in other domains.
The N-terminal disordered tail encompassing the polyQ tract and missing from the density map includes the first 94 residues.
Cross-references: EMDB:EMD-4937
PDB:6RMH
Protein: DP04129 (UniProt P42858)
Region: residues 1323	to 1351
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Besides the polyQ tract, a large portion of N-HEAT domain (aa 409–666 in Q23-HTT) in the high-resolution cryo-EM structure is unstructured in addition to several small regions in other domains.
One of these additional smaller IDRs streches between aa. 1323-1351 within the N-HEAT domain.
Cross-references: EMDB:EMD-4937
PDB:6RMH
Protein: DP04129 (UniProt P42858)
Region: residues 1376	to 1422
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Besides the polyQ tract, a large portion of N-HEAT domain (aa 409–666 in Q23-HTT) in the high-resolution cryo-EM structure is unstructured in addition to several small regions in other domains.
One of these additional smaller IDRs streches between aa. 1376-1422 within the N-HEAT domain.
Cross-references: EMDB:EMD-4937
PDB:6RMH
Protein: DP04129 (UniProt P42858)
Region: residues 1859	to 1885
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Besides the polyQ tract, a large portion of N-HEAT domain (aa 409–666 in Q23-HTT) in the high-resolution cryo-EM structure is unstructured in addition to several small regions in other domains.
One of these additional smaller IDRs streches between aa. 1859-1885 within the Bridge domain.
Cross-references: EMDB:EMD-4937
PDB:6RMH
Protein: DP04129 (UniProt P42858)
Region: residues 2329	to 2351
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Besides the polyQ tract, a large portion of N-HEAT domain (aa 409–666 in Q23-HTT) in the high-resolution cryo-EM structure is unstructured in addition to several small regions in other domains.
One of these additional smaller IDRs streches between aa. 2329-2351 within the C-HEAT domain.
Cross-references: EMDB:EMD-4937
PDB:6RMH
Protein: DP04129 (UniProt P42858)
Region: residues 2631	to 2664
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Besides the polyQ tract, a large portion of N-HEAT domain (aa 409–666 in Q23-HTT) in the high-resolution cryo-EM structure is unstructured in addition to several small regions in other domains.
One of these additional smaller IDRs streches between aa. 2631-2664 within the C-HEAT domain.
Cross-references: EMDB:EMD-4937
PDB:6RMH
Protein: DP04129 (UniProt P42858)
Region: residues 3103	to 3142
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Besides the polyQ tract, a large portion of N-HEAT domain (aa 409–666 in Q23-HTT) in the high-resolution cryo-EM structure is unstructured in addition to several small regions in other domains.
One of these additional smaller IDRs streches between aa. 3103-3142 within the C-HEAT domain.
Cross-references: EMDB:EMD-4937
PDB:6RMH
Protein: DP04129 (UniProt P42858)
Region: residues 1862	to 1874
Annotation: phosphorylation display site (Disorder function)
Evidence: liquid chromatography coupled with tandem mass spectrometry evidence used in manual assertion
Supporting statements:
Besides the polyQ tract, a large portion of N-HEAT domain (aa 409–666 in Q23-HTT) in the high-resolution cryo-EM structure is unstructured in addition to several small regions in other domains.
Most phosphorylation sites except S2114, S2116, S2423, and S2550 located in the C-HEAT domain are located in disordered regions in the cryo-EM structures.
Several HTT phosphorylation sites were identified by MS and are listed along the length of the HTT amino acid sequence.
Phosphosites on Figure 6A in the IDR streching between aa. 1859-1885 within the Bridge domain: pS1864 and pS1876. With UniProt numbering these correspond to pS1862 and pS1874.
Protein: DP04129 (UniProt P42858)
Region: residues 2333	to 2337
Annotation: phosphorylation display site (Disorder function)
Evidence: liquid chromatography coupled with tandem mass spectrometry evidence used in manual assertion
Supporting statements:
Besides the polyQ tract, a large portion of N-HEAT domain (aa 409–666 in Q23-HTT) in the high-resolution cryo-EM structure is unstructured in addition to several small regions in other domains.
Most phosphorylation sites except S2114, S2116, S2423, and S2550 located in the C-HEAT domain are located in disordered regions in the cryo-EM structures.
Several HTT phosphorylation sites were identified by MS and are listed along the length of the HTT amino acid sequence.
Phosphosite on Figure 6A and Suppl. fig. S5A in the IDR streching between aa. 2329-2351 within the C-HEAT domain: pT2337. With UniProt numbering this corresponds to pT2335. The curated phosphorylation display site was annotated with 2-residue flanking regions in both direction.
Protein: DP04129 (UniProt P42858)
Region: residues 327	to 346
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Besides the polyQ tract, a large portion of N-HEAT domain (aa 409–666 in Q23-HTT) in the high-resolution cryo-EM structure is unstructured in addition to several small regions in other domains.
One of these additional smaller IDRs streches between aa. 327-346 within the N-HEAT domain.
Cross-references: EMDB:EMD-4937
PDB:6RMH
Protein: DP04129 (UniProt P42858)
Region: residues 964	to 981
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Besides the polyQ tract, a large portion of N-HEAT domain (aa 409–666 in Q23-HTT) in the high-resolution cryo-EM structure is unstructured in addition to several small regions in other domains.
One of these additional smaller IDRs streches between aa. 964-981 within the N-HEAT domain.
Cross-references: EMDB:EMD-4937
PDB:6RMH
Protein: DP04129 (UniProt P42858)
Region: residues 1107	to 1124
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Besides the polyQ tract, a large portion of N-HEAT domain (aa 409–666 in Q23-HTT) in the high-resolution cryo-EM structure is unstructured in addition to several small regions in other domains.
One of these additional smaller IDRs streches between aa. 1107-1124 within the N-HEAT domain.
Cross-references: EMDB:EMD-4937
PDB:6RMH
Protein: DP04129 (UniProt P42858)
Region: residues 2476	to 2494
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Besides the polyQ tract, a large portion of N-HEAT domain (aa 409–666 in Q23-HTT) in the high-resolution cryo-EM structure is unstructured in addition to several small regions in other domains.
One of these additional smaller IDRs streches between aa. 2476-2494 within the C-HEAT domain.
Cross-references: EMDB:EMD-4937
PDB:6RMH
Protein: DP04129 (UniProt P42858)
Region: residues 2930	to 2948
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Besides the polyQ tract, a large portion of N-HEAT domain (aa 409–666 in Q23-HTT) in the high-resolution cryo-EM structure is unstructured in addition to several small regions in other domains.
One of these additional smaller IDRs streches between aa. 2930-2948 within the C-HEAT domain.
Cross-references: EMDB:EMD-4937
PDB:6RMH
Protein: DP04129 (UniProt P42858)
Region: residues 2338	to 2342
Annotation: phosphorylation display site (Disorder function)
Evidence: liquid chromatography coupled with tandem mass spectrometry evidence used in manual assertion
Supporting statements:
Besides the polyQ tract, a large portion of N-HEAT domain (aa 409–666 in Q23-HTT) in the high-resolution cryo-EM structure is unstructured in addition to several small regions in other domains.
Most phosphorylation sites except S2114, S2116, S2423, and S2550 located in the C-HEAT domain are located in disordered regions in the cryo-EM structures.
Several HTT phosphorylation sites were identified by MS and are listed along the length of the HTT amino acid sequence.
Phosphosite on Figure 6A and Suppl. fig. S5A in the IDR streching between aa. 2329-2351 within the C-HEAT domain: pS2342. With UniProt numbering this corresponds to pS2340. The curated phosphorylation display site was annotated with 2-residue flanking regions in both direction.
Protein: DP04130 (UniProt P32911)
Region: residues 1	to 25
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance evidence used in manual assertion
Supporting statements:
eIF1 comprises an unstructured N-terminal tail (NTT) and a globular domain with a β1-β2-α1-β3-β4-α2-β5 fold (Fletcher et al., 1999, Reibarkh et al., 2008) (Figure 3A; Table S4).
Cross-references: PDB:2RVH
Protein: DP04131 (UniProt Q5TDH0)
Region: residues 116	to 133
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance evidence used in manual assertion
Supporting statements:
Both the N- and C-terminal parts of HDD form unstructured linker regions, allowing flexibility between the individual structured domains of hDdi2.
Cross-references: PDB:5K57
Protein: DP04131 (UniProt Q5TDH0)
Region: residues 116	to 133
Annotation: flexible linker (Disorder function)
Evidence: nuclear magnetic resonance evidence used in manual assertion
Supporting statements:
Both the N- and C-terminal parts of HDD form unstructured linker regions, allowing flexibility between the individual structured domains of hDdi2.
Cross-references: PDB:5K57
Protein: DP04131 (UniProt Q5TDH0)
Region: residues 192	to 212
Annotation: flexible linker (Disorder function)
Evidence: nuclear magnetic resonance evidence used in manual assertion
Supporting statements:
Both the N- and C-terminal parts of HDD form unstructured linker regions, allowing flexibility between the individual structured domains of hDdi2.
Cross-references: PDB:5K57
Protein: DP04131 (UniProt Q5TDH0)
Region: residues 192	to 212
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance evidence used in manual assertion
Supporting statements:
Both the N- and C-terminal parts of HDD form unstructured linker regions, allowing flexibility between the individual structured domains of hDdi2.
Cross-references: PDB:5K57
Protein: DP04132 (UniProt Q9NZC2)
Region: residues 131	to 174
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Residues 19–21 and 130–140 were also disordered in the PS-soaked structure.
Residue 130 was only modeled in one chain, residues 131-174 were not resolvable in any of the protein chains due their disordered nature.
Cross-references: PDB:6B8O
Protein: DP04132 (UniProt Q9NZC2)
Region: residues 189	to 206
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
As determined here for TREM2, an unfolded region manifested by an extreme drop in the order parameter can be intrinsically present in a substrate TMH and oriented toward the outside of the hydrophobic membrane interior. The most critical amino acid residue in TREM2‐TMH is the positively charged K186, that is located within the hydrophobic interior of the membrane and which is required for complex formation with DAP12 (Fig 2). Without DAP12, the presence of an unpaired charge in the membrane leads to the formation of a partially unwound helical region with increased conformational dynamics.
S2 values of around 0.9 for the ordered first half of the TMH, of around 0.6 for the unstructured kink region, and 0.7 for the C‐terminal helix can be extracted.
Strikingly, the site of intramembrane cleavage of wt TREM2 correlates well with the observed enhanced dynamics between amino acids 189 and 193 (Fig 3A).
Taken together, these data establish that structural dynamics of TREM2 at the C‐terminal end of the TMH determine the site where the initial ε‐cleavage takes place.
Cross-references: BMRB:50263
PDB:6Z0G
Protein: DP04132 (UniProt Q9NZC2)
Region: residues 189	to 198
Annotation: disorder to order (Structural transition)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
TREM2‐TMH structure is stabilized by binding to DAP12 or by charge removal
In line with the previous finding that DAP12 binding leads to TREM2‐CTF stabilization (Zhong et al, 2015), we here were able to show that this interaction leads to the formation of a continuous α‐helix ranging from residues 173 to 198 without the previously kinked region (Fig 2D, Table 1). 
Cross-references: BMRB:50263
BMRB:50265
PDB:6Z0G
PDB:6Z0I
Protein: DP04132 (UniProt Q9NZC2)
Region: residues 190	to 194
Annotation: limited proteolysis display site (Disorder function)
Evidence: protein mass spectrometry evidence used in manual assertion
Supporting statements:
Immunoprecipitation of the soluble fraction using an anti‐HA antibody revealed γ‐secretase‐dependent generation of the TREM2 ICD (Fig 5B). Immunoprecipitated ICDs were subjected to mass spectrometry as described previously (Fleck et al, 2016). This revealed a major peak at 5596,20 Da for wt TREM2, which was absent at 4°C and reduced upon treatment with L‐685,458 (Fig 5C). This peak corresponds to a major ε‐cleavage site after amino acid 192 within the TMH (Fig 5C–E).
MALDI MS analysis of the ε‐cleavage sites of wt and mutant TREM2 C‐terminal fragments. Mass spectrometry reveals ε‐cleavage C‐terminal of A192 for the wt CTF.
Interestingly, the K186A mutation, which strongly stabilizes the α‐helical structure of the TREM2 TMH, abolishes cleavage after amino acid 192 and shifts the ε‐cleavage to a new site after amino acid 195 and to a lower extent to 193 (Fig 5C–E).
Protein: DP04133 (UniProt P02649)
Region: residues 19	to 40
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The apoE3 model contains residues 23-81 and 92-164 whereas the apoE2 Ala-154 model is truncated at glutamine 163. The missing residues, which constitute about 30% of the full 22,000 M, fragment are all located at one extreme of the four-helix bundle. We believe them to be completely disordered and thus indicate a likely cause of the rather high terminal R-values.
The numbering applied by the authors is without the 18-residue-long signal peptide.
Cross-references: PDB:1NFN
Protein: DP04133 (UniProt P02649)
Region: residues 100	to 109
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The apoE3 model contains residues 23-81 and 92-164 whereas the apoE2 Ala-154 model is truncated at glutamine 163. The missing residues, which constitute about 30% of the full 22,000 M, fragment are all located at one extreme of the four-helix bundle. We believe them to be completely disordered and thus indicate a likely cause of the rather high terminal R-values.
The numbering applied by the authors is without the 18-residue-long signal peptide.
Cross-references: PDB:1NFN
Protein: DP04133 (UniProt P02649)
Region: residues 183	to 209
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The apoE3 model contains residues 23-81 and 92-164 whereas the apoE2 Ala-154 model is truncated at glutamine 163. The missing residues, which constitute about 30% of the full 22,000 M, fragment are all located at one extreme of the four-helix bundle. We believe them to be completely disordered and thus indicate a likely cause of the rather high terminal R-values.
The numbering applied by the authors is without the 18-residue-long signal peptide.
Cross-references: PDB:1NFN
Protein: DP04133 (UniProt P02649)
Region: residues 184	to 242
Annotation: disorder (Structural state)
Evidence: in vitro cleavage assay evidence used in manual assertion
Supporting statements:
The results clearly demonstrate that apoE3 contains two proteolytic-resistant regions separated by a region, residues 166-224, that is highly susceptible to proteolysis. The results are consistent with apoE3 containing two domains, an amino-terminal domain containing residues 20-165 and a carboxyl-terminal domain containing residues 225-299.
The numbering applied by the authors is without the 18-residue-long signal peptide.
Protein: DP04133 (UniProt P02649)
Region: residues 19	to 41
Annotation: disorder (Structural state)
Evidence: fluorescence resonance energy transfer evidence used in manual assertion
Supporting statements:
ApoE comprises four different regions: the N-terminal tail (residues 1 to 23), the four-helix bundle (24 to 167) (20–22), the hinge region (168 to 205), and the C-terminal domain (206 to 299) (Fig. 1).
Conversely, the population at higher transfer efficiency follows the expected trend of a dynamic conformational ensemble, that is, an ensemble of interdye distances that are sampled in a timescale much shorter than the residence time of the protein in the confocal volume. Interestingly, the results are better described using a wormlike chain distribution with persistence length lp (an estimate of the minimal flexible segment) equal to 2.5 nm and contour length lc (the maximum extension of the probed region) equal to 7.7 nm (SI Appendix, Fig. S2).
The numbering applied by the authors is without the 18-residue-long signal peptide.
Protein: DP04133 (UniProt P02649)
Region: residues 186	to 223
Annotation: disorder (Structural state)
Evidence: fluorescence resonance energy transfer evidence used in manual assertion
Supporting statements:
ApoE comprises four different regions: the N-terminal tail (residues 1 to 23), the four-helix bundle (24 to 167) (20–22), the hinge region (168 to 205), and the C-terminal domain (206 to 299) (Fig. 1).
The population associated with lower mean transfer efficiency (E = 0.62 ± 0.02) accounts for 60% of the observed molecules, whereas the high transfer efficiency population (E = 0.83 ± 0.02) accounts for the remaining 40%, corresponding to a free energy difference between these states of 1.0 ± 0.2 RT (SI Appendix, Tables S1 and S2). The asymmetry of the distribution persists with increasing denaturant concentrations, with both populations shifting toward lower transfer efficiencies (Fig. 3), as expected for disordered or partially disordered regions (31). Comparing lifetime and transfer efficiency indicates that both populations reflect dynamic averages that, similar to the case of the N-terminal tail, we can describe in terms of a wormlike chain (SI Appendix, Fig. S2).
The numbering applied by the authors is without the 18-residue-long signal peptide.
Protein: DP04133 (UniProt P02649)
Region: residues 19	to 40
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Our final model lacks amino acid residues 1 to 22 and 167 to 191. At both ends of the modeled region, density is well determined but quickly disappears outside the model. Electrophoresis of the crystalized protein demonstrated that the complete 22-kD fragment was present; that is,the missing regions were not absent as a result of proteolysis. We believe residues 1 to 22 and 167 to 191 are disordered in the crystal and are not missing because of systematic phasing errors
The numbering applied by the authors is without the 18-residue-long signal peptide.
Cross-references: PDB:1LPE
Protein: DP04133 (UniProt P02649)
Region: residues 185	to 209
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Our final model lacks amino acid residues 1 to 22 and 167 to 191. At both ends of the modeled region, density is well determined but quickly disappears outside the model. Electrophoresis of the crystalized protein demonstrated that the complete 22-kD fragment was present; that is,the missing regions were not absent as a result of proteolysis. We believe residues 1 to 22 and 167 to 191 are disordered in the crystal and are not missing because of systematic phasing errors
The numbering applied by the authors is without the 18-residue-long signal peptide.
Cross-references: PDB:1LPE
Protein: DP04133 (UniProt P02649)
Region: residues 183	to 209
Annotation: disorder (Structural state)
Evidence: in vitro cleavage assay evidence used in manual assertion
Supporting statements:
Digestion of apoE with a battery of proteases shows that amino acids 1 to 20 and 165 to 191 are susceptible to proteolysis and thus likely to be unstructured (Fig.1) (2).
The numbering applied by the authors is without the 18-residue-long signal peptide.
Protein: DP04133 (UniProt P02649)
Region: residues 19	to 38
Annotation: disorder (Structural state)
Evidence: in vitro cleavage assay evidence used in manual assertion
Supporting statements:
Digestion of apoE with a battery of proteases shows that amino acids 1 to 20 and 165 to 191 are susceptible to proteolysis and thus likely to be unstructured (Fig.1) (2).
The numbering applied by the authors is without the 18-residue-long signal peptide.