LiteFold/DisProt huggingface dataset:
Protein: DP00304 (UniProt P31751)
Region: residues 298	to 310
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Akt2 residues omitted from the model because of disorder include the N-terminal residues 143–145, residues 190–201 of α helix C, residues 298–310 of the activation loop, and C-terminal residues 441–481.
Cross-references: PDB:1MRV
PDB:1MRY
Protein: DP00304 (UniProt P31751)
Region: residues 297	to 312
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
In all three crystal forms of PKB, a contiguous region of the activation segment (residues 297 to 312) located between the invariant DFG and APE motifs, and including (p)Thr 309, is disordered.
Cross-references: PDB:1GZN
PDB:1GZO
PDB:1GZK
Protein: DP00304 (UniProt P31751)
Region: residues 442	to 460
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Moreover, in these structures, electron density for residues C-terminal to Asp 441 is not visible, suggesting that they are conformational disordered. However, in the ΔPH-PKB structure, which contains a nonphosphorylated hydrophobic motif and therefore retains the potential to interact with the N lobe, we are also unable to detect visible electron density for residues C-terminal to Asp 441, indicating that the hydrophobic motif is mobile.
Cross-references: PDB:1GZK
PDB:1GZO
Protein: DP00304 (UniProt P31751)
Region: residues 442	to 480
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Moreover, in these structures, electron density for residues C-terminal to Asp 441 is not visible, suggesting that they are conformational disordered. However, in the ΔPH-PKB structure, which contains a nonphosphorylated hydrophobic motif and therefore retains the potential to interact with the N lobe, we are also unable to detect visible electron density for residues C-terminal to Asp 441, indicating that the hydrophobic motif is mobile.
Cross-references: PDB:1GZN
Protein: DP00304 (UniProt P31751)
Region: residues 441	to 481
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Akt2 residues omitted from the model because of disorder include the N-terminal residues 143–145, residues 190–201 of α helix C, residues 298–310 of the activation loop, and C-terminal residues 441–481.
In the structure of inactive Akt2-KD, the C-terminal chain extends over the C-terminal lobe and terminates near the ATP binding site, with the remaining 40 residues disordered.
Cross-references: PDB:1MRV
PDB:1MRY
Protein: DP00304 (UniProt P31751)
Region: residues 190	to 201
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Akt2 residues omitted from the model because of disorder include the N-terminal residues 143–145, residues 190–201 of α helix C, residues 298–310 of the activation loop, and C-terminal residues 441–481.
The majority of α helix C in Akt2-KD, however, is disordered.
A distinguishing feature of the Akt2-KD structure is that the first eight residues of α helix C in Akt2-KD are disordered.
Cross-references: PDB:1MRV
PDB:1MRY
Protein: DP00304 (UniProt P31751)
Region: residues 298	to 310
Annotation: molecular function activator activity (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
Akt2 residues omitted from the model because of disorder include the N-terminal residues 143–145, residues 190–201 of α helix C, residues 298–310 of the activation loop, and C-terminal residues 441–481.
Protein: DP00304 (UniProt P31751)
Region: residues 472	to 476
Annotation: phosphorylation display site (Disorder function)
Evidence: mass spectrometry evidence used in manual assertion
Supporting statements:
Activation of PKB by Ser 474 phosphorylation occurs via a mechanism involving a disorder to order transition of the αC helix of the N-terminal lobe, induced by the association of a phosphorylated hydrophobic motif, with concomitant ordering and restructuring of the activation segment and alignment of catalytic site residues.
Phosphorylation of Ser 474 augments the activity of PDK1-phosphorylated PKB by 7- to 10-fold (Alessi et al., 1996), such that phosphorylation of both residues results in greater than 1000-fold increased protein kinase activity.
The site of C-terminal regulatory phosphorylation of PKB (Ser 474) is within a hydrophobic sequence motif (F-x-x-F-[S/T]-Y), conserved within a large proportion of AGC kinases Keranen et al. 1995, Pearson et al. 1995.
Region including the phosphorylated Ser474.
Protein: DP00306 (UniProt Q07108)
Region: residues 64	to 84
Annotation: disorder (Structural state)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
The stem region, which includes residues Gly64 to Val82 in the crystallized recombinant protein, is largely disordered in the structure, except for three residues (Ser78, Asp79, and Ser80) wedged between two symmetry-related molecules.
Cross-references: PDB:1FM5
Protein: DP00309 (UniProt P00533)
Region: residues 985	to 1012
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
This region lacks electron density indicating it is disordered.
Cross-references: PDB:1M14
Protein: DP00309 (UniProt P00533)
Region: residues 989	to 1000
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
This region lacks electron density indicating it is disordered.
Cross-references: PDB:1M17
Protein: DP00309 (UniProt P00533)
Region: residues 668	to 1210
Annotation: disorder (Structural state)
Evidence: protein hydrogen-deuterium exchange mass spectrometry evidence used in manual assertion
Supporting statements:
The most striking result can be seen within the EGFR CTT where we observe that exchange reaches a plateau very rapidly, often within 5 s of exchange, and the %nex values are indicated by orange and red colors on the heat map. This rapid exchange indicates that the tail is unprotected from exchange when compared with the kinase domain. The observed rapid exchange behavior is characteristic of a highly dynamic and/or frequently exchange-competent conformational state, meaning amide hydrogen bonding between residues is transient or weak in these regions.
Protein: DP00309 (UniProt P00533)
Region: residues 668	to 1210
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
However, the CD spectrum observed for EGFR CTT shows a minimum between 195 and 200 nm, which is a characteristic of disordered proteins (Fig. 5A). However, the slightly negative ellipticity at 222 nm indicates the possibility of residual secondary structure. Analysis via the CDSSTR algorithm, an algorithm used to assign secondary structure composition to CD spectra, shows 77% unordered character in the EGFR CTT spectrum (Fig. 5C). These results suggest that much of the EGFR CTT construct has an unfolded conformation in solution.
Protein: DP00309 (UniProt P00533)
Region: residues 668	to 1210
Annotation: disorder (Structural state)
Evidence: gel-filtration evidence used in manual assertion
Supporting statements:
EGFR CTT elutes from the SEC column before 13 ml of buffer volume. Despite having a lower molecular weight, the EGFR CTT elutes earlier than carbonic anhydrase, which elutes just after 15 ml of buffer. The expected Stokes radius of carbonic anhydrase is 2.4 nm (44). This earlier elution indicates that the EGFR CTT conformational ensemble is more extended than that of carbonic anhydrase, which has a globular structure.
Protein: DP00309 (UniProt P00533)
Region: residues 668	to 1210
Annotation: disorder (Structural state)
Evidence: dynamic light scattering assay evidence used in manual assertion
Supporting statements:
The EGFR CTT, which has a molecular mass of 26 kDa, was determined to have a hydrodynamic radius of 5.3 nm. For a comparison, we also analyzed BSA, a globular protein with a molecular mass of 66 kDa, and the hydrodynamic radius of BSA was measured to be 4.8 nm. This demonstrates that EGFR CTT has a larger hydrodynamic radius than a globular protein more than 2.5 times its size.
Protein: DP00309 (UniProt P00533)
Region: residues 668	to 1210
Annotation: disorder (Structural state)
Evidence: analytical ultracentrifugation evidence used in manual assertion
Supporting statements:
For a globular protein, the expected f/fmin would fall between 1.15 and 1.3 (47–49). We determined the f/fmin value for EGFR CTT to be much greater, at 1.77, which is consistent with this being an IDR.
Protein: DP00309 (UniProt P00533)
Region: residues 668	to 1210
Annotation: disorder (Structural state)
Evidence: small-angle X-ray scattering evidence used in manual assertion
Supporting statements:
In contrast, EGFR CTT shows a hyperbolic shape on the Kratky plot, indicating an intrinsically disordered region (Fig. 7C).
Protein: DP00309 (UniProt P00533)
Region: residues 1067	to 1071
Annotation: phosphorylation display site (Disorder function)
Evidence: qualitative western immunoblotting evidence used in manual assertion
Supporting statements:
We show, through Western blotting identification of specific phosphorylated tyrosine residues (EGFR Tyr-1068 and Tyr-1173) in the EGFR CTT (Fig. 4C), that the EGFR CTT is recognized and phosphorylated by the EGFR kinase domain even when these two domains are expressed as separated constructs.
There is some discrepancy in the numbering. Tyr-1068 mentioned in the paper corresponds to Tyr1069 in UniProt sequence, while Tyr-1173 corresponds to Tyr1172 in UniProt sequence.
Protein: DP00309 (UniProt P00533)
Region: residues 1170	to 1174
Annotation: phosphorylation display site (Disorder function)
Evidence: qualitative western immunoblotting evidence used in manual assertion
Supporting statements:
We show, through Western blotting identification of specific phosphorylated tyrosine residues (EGFR Tyr-1068 and Tyr-1173) in the EGFR CTT (Fig. 4C), that the EGFR CTT is recognized and phosphorylated by the EGFR kinase domain even when these two domains are expressed as separated constructs.
There is some discrepancy in the numbering. Tyr-1068 mentioned in the paper corresponds to Tyr1069 in UniProt sequence, while Tyr-1173 corresponds to Tyr1172 in UniProt sequence.
Protein: DP00309 (UniProt P00533)
Region: residues 668	to 1210
Annotation: protein binding (Molecular function)
Evidence: glutathione S-transferase pull-down assay evidence used in manual assertion
Supporting statements:
However, once phosphorylated, EGFR CTT was bound by GST-Grb2-SH2 and was pulled down by glutathione-agarose.
The interaction is dependent on phosphorylation of particular Tyr residues within the EGFR C-terminal tail.
Protein: DP00310 (UniProt P62495)
Region: residues 333	to 342
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The final structure includes residues 5 to 422. Three regions of the polypeptide are not visible in the electron density map and are assumed to be disordered, namely residues 333–342 and 358–370 and 15 residues at the C terminus.
Cross-references: PDB:1DT9
Protein: DP00310 (UniProt P62495)
Region: residues 358	to 370
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The final structure includes residues 5 to 422. Three regions of the polypeptide are not visible in the electron density map and are assumed to be disordered, namely residues 333–342 and 358–370 and 15 residues at the C terminus.
Cross-references: PDB:1DT9
Protein: DP00310 (UniProt P62495)
Region: residues 423	to 437
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The final structure includes residues 5 to 422. Three regions of the polypeptide are not visible in the electron density map and are assumed to be disordered, namely residues 333–342 and 358–370 and 15 residues at the C terminus.
Cross-references: PDB:1DT9
Protein: DP00310 (UniProt P62495)
Region: residues 414	to 437
Annotation: disorder (Structural state)
Evidence: heteronuclear single quantum coherence spectroscopy evidence used in manual assertion
Supporting statements:
There are many signals with high intensity due to increased mobility of corresponding residues. These are primarily from unstructured C-terminal tail (residues 414–437) and minidomain 329–372.
Protein: DP00310 (UniProt P62495)
Region: residues 329	to 372
Annotation: disorder (Structural state)
Evidence: heteronuclear single quantum coherence spectroscopy evidence used in manual assertion
Supporting statements:
There are many signals with high intensity due to increased mobility of corresponding residues. These are primarily from unstructured C-terminal tail (residues 414–437) and minidomain 329–372.
Protein: DP00315 (UniProt O43464)
Region: residues 344	to 358
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The N-terminal 5 residues and a 15-residue linker sequence are disordered in the crystals.
Cross-references: PDB:1LCY
Protein: DP00315 (UniProt O43464)
Region: residues 280	to 292
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
There were notable gaps in the electron density for the N- and C-termini, within the L3 loop (between residues R280-V292 with small variations in the different structures), and for the linker region between the protease and PDZ domains (G345-S357) common for all the structures described in this work (Figure 1 and Supplementary Information).
Cross-references: PDB:5M3N
Protein: DP00315 (UniProt O43464)
Region: residues 344	to 358
Annotation: flexible linker (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
On the other end, the PDZ domain is covalently linked to the protease domain through a flexible linker sequence (residues 211–225).
Cross-references: PDB:1LCY
Protein: DP00315 (UniProt O43464)
Region: residues 344	to 357
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
There were notable gaps in the electron density for the N- and C-termini, within the L3 loop (between residues R280-V292 with small variations in the different structures), and for the linker region between the protease and PDZ domains (G345-S357) common for all the structures described in this work (Figure 1 and Supplementary Information).
Cross-references: PDB:5M3N
Protein: DP00315 (UniProt O43464)
Region: residues 344	to 357
Annotation: flexible linker (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
There were notable gaps in the electron density for the N- and C-termini, within the L3 loop (between residues R280-V292 with small variations in the different structures), and for the linker region between the protease and PDZ domains (G345-S357) common for all the structures described in this work (Figure 1 and Supplementary Information).
Cross-references: PDB:5M3N
Protein: DP00315 (UniProt O43464)
Region: residues 345	to 358
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
1LCY and 5FHT have 3 unresolved regions, viz: the N-terminal IAP-binding motif 134AVPSP138 and 134AVPSPPPA141; L3β8~β9 282ARDLGLPQT290 and 281PARDLG286; and the PD~PDZ linker 344RGEKKNSSSGISGSQ358 and 345GEKKNSSSGISGSQ358, respectively.
Cross-references: PDB:5FHT
Protein: DP00315 (UniProt O43464)
Region: residues 345	to 358
Annotation: flexible linker (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
1LCY and 5FHT have 3 unresolved regions, viz: the N-terminal IAP-binding motif 134AVPSP138 and 134AVPSPPPA141; L3β8~β9 282ARDLGLPQT290 and 281PARDLG286; and the PD~PDZ linker 344RGEKKNSSSGISGSQ358 and 345GEKKNSSSGISGSQ358, respectively.
Cross-references: PDB:5FHT
Protein: DP00319 (UniProt O15350)
Region: residues 549	to 564
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The high R factor and R free are consistent with a large extent of disorder (23 residues of 80). There is sufficient volume to accommodate these missing residues (seven at the N-terminus and 16 at the C-terminus) in the crystal lattice.
The first seven N-terminal residues, including two plasmid-encoded residues and residues 487-491, and the C-terminal residues 549-564 are disordered.
Cross-references: PDB:1DXS
Protein: DP00320 (UniProt P05121)
Region: residues 355	to 370
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
As expected, the electron density of the solvent-exposed flexible RCL (Ser331–Pro349) is missing and reflects the ability of the RCL to adopt different conformations suitable for the interaction with target proteases (10).
The numbering of the IDR that includes the reactive center loop (RCL) of PAI-1, corresponds to region 355-370 of the associated UniProt sequence, since PDB:3Q02 spans residues 24-402 of the protein.
Cross-references: PDB:3Q02
PDB:3Q03
Protein: DP00320 (UniProt P05121)
Region: residues 361	to 370
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Dashed lines indicate disordered residues in the reactive center loop (RCL) of PAI-1 and residues leading to the RGD sequence of somatomedin B.
The final model includes residues 6–337 and 348–379 of PAI-1 and 3–39 of SMB.
The numbering of the IDR that includes the reactive center loop (RCL) of PAI-1, corresponds to region 361-370 of the associated UniProt sequence, since PDB:1OC0 spans residues 24-402 of the protein.
Cross-references: PDB:1OC0
Protein: DP00320 (UniProt P05121)
Region: residues 355	to 370
Annotation: molecular function regulator (Molecular function)
Evidence: combinatorial experimental and author inference evidence contained in single publication used in manual assertion
Supporting statements:
The numbering of the IDR that includes the reactive center loop (RCL) of PAI-1, corresponds to region 355-370 of the associated UniProt sequence, since PDB:3Q02 spans residues 24-402 of the protein.
As expected, the electron density of the solvent-exposed flexible RCL (Ser331–Pro349) is missing and reflects the ability of the RCL to adopt different conformations suitable for the interaction with target proteases (10).
Cross-references: PDB:3Q02
PDB:3Q03
Protein: DP00322 (UniProt P11309)
Region: residues 14	to 31
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Most residues in the Pim-1 structures are well resolved, except for the N-terminal residues 14–31 and the C-terminal residues 309–313.
Cross-references: PDB:1XQZ
Protein: DP00324 (UniProt P09651)
Region: residues 92	to 102
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Three regions were not modeled because of poor electron density: the first seven residues at the N-terminus, the last 16 residues at the C-terminus and the internal linker residues Arg92–Leu102. These regions were disordered in the original 1.75 and 1.9 Å structures (35,36) and they remained uninterpretable even in the present high resolution analysis.
Cross-references: PDB:1L3K
Protein: DP00324 (UniProt P09651)
Region: residues 92	to 102
Annotation: flexible linker (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Three regions were not modeled because of poor electron density: the first seven residues at the N-terminus, the last 16 residues at the C-terminus and the internal linker residues Arg92–Leu102. These regions were disordered in the original 1.75 and 1.9 Å structures (35,36) and they remained uninterpretable even in the present high resolution analysis.
The disordered region is positioned between two RRM domains.
Cross-references: PDB:1L3K
Protein: DP00324 (UniProt P09651)
Region: residues 182	to 196
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Three regions were not modeled because of poor electron density: the first seven residues at the N-terminus, the last 16 residues at the C-terminus and the internal linker residues Arg92–Leu102. These regions were disordered in the original 1.75 and 1.9 Å structures (35,36) and they remained uninterpretable even in the present high resolution analysis.
Cross-references: PDB:1L3K
Protein: DP00324 (UniProt P09651)
Region: residues 92	to 102
Annotation: disorder to order (Structural transition)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
Second, the linker connecting the two RRMs becomes ordered on TR2 binding (Fig. 2A).
Cross-references: PDB:2UP1
Protein: DP00324 (UniProt P09651)
Region: residues 92	to 102
Annotation: DNA binding (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
Both regions make important contacts with DNA (see below).
The inter-RRM linker segment is defined to include amino acids 90–105. Three residues in this segment make direct contacts with DNA bases. Arg-92 makes contacts with three bases, Gua-4, Gua-5, and Thy-7, and the guanidino moiety is locked between the three bases (Fig.4 and 5A). Ser-95 makes a hydrogen bond with the N2 atom of Gua-4. The imidazole ring of His-101 stacks with the purine ring of Ade-3, which is sandwiched between His-101 and Phe-17.
Cross-references: PDB:2UP1
Protein: DP00324 (UniProt P09651)
Region: residues 92	to 102
Annotation: flexible linker (Disorder function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
The inter-RRM linker segment is defined to include amino acids 90–105.
Second, the linker connecting the two RRMs becomes ordered on TR2 binding (Fig. 2A).
Cross-references: PDB:2UP1