LiteFold/DisProt huggingface dataset:
Protein: DP02731 (UniProt Q5U651)
Region: residues 187	to 197
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The current RRA model excludes many residues; 141–142 (N terminus), 154–158 (loop β1-β2), 187–197 (loop α1-β3), 212–220 (loop β3-β4), and 268–285 (C terminus, not part of the RRA) as highlighted in Figures 2A and 2C, and many side chains were also poorly defined in the electron density map.
Similar to the free RA domain structure, the current Rasip1 RA domain model excludes many residues, 141–142 (N terminus), 186–195 (loop α1-β3), 212–220 (loop β3-β4), and 268–285 (C terminus), and many side chains were also poorly defined in the electron density map.
This observation was in agreement with the NMR spectrum of the complex, which showed that most of the sharp peaks remained sharp when in complex with Rap1; this suggested that the unstructured loops remained unstructured in the complex.
The Rasip1 RA domain contains many unstructured loops as demonstrated by both the presence of many sharp peaks in the NMR sfHMQC and the absence of electron density in the crystal structure.
Cross-references: PDB:5KHQ
PDB:5KHO
Protein: DP02732 (UniProt Q8IWJ2)
Region: residues 1547	to 1569
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
In addition, flexible regions were detected downstream of the GRIP domain (∼20 residues), and spanning ∼40 residues upstream of residue 1527
Cross-references: PDB:3BBP
Protein: DP02733 (UniProt P20340)
Region: residues 175	to 206
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
We present a structure-derived model for dual GTPase membrane attachment that highlights the potential ability of Rab GTPases to reach binding partners at a significant distance from the membrane via their unstructured and membrane-anchored, hypervariable domains.
An important aspect of our model is the possibility that Rab proteins may reach some distance from the membrane (up to ∼10nm) to bind to an effector protein, due to the unstructured nature of a Rab protein's ∼30 residue, membrane anchored, C-terminal hypervariable domain
Cross-references: PDB:3BBP
Protein: DP02733 (UniProt P20340)
Region: residues 175	to 206
Annotation: localization (Biological process)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
We present a structure-derived model for dual GTPase membrane attachment that highlights the potential ability of Rab GTPases to reach binding partners at a significant distance from the membrane via their unstructured and membrane-anchored, hypervariable domains.
An important aspect of our model is the possibility that Rab proteins may reach some distance from the membrane (up to ∼10nm) to bind to an effector protein, due to the unstructured nature of a Rab protein's ∼30 residue, membrane anchored, C-terminal hypervariable domain
Cross-references: PDB:3BBP
Protein: DP02734 (UniProt P21517)
Region: residues 1	to 131
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Based on the crystallographic structure, it has been interpreted that the N-terminal region of the enzyme (Met1-Phe131) might be unstructured or flexible.
Cross-references: PDB:5BN7
Protein: DP02734 (UniProt P21517)
Region: residues 1	to 131
Annotation: disorder (Structural state)
Evidence: cleavage assay evidence used in manual assertion
Supporting statements:
Based on the crystallographic structure, it has been interpreted that the N-terminal region of the enzyme (Met1-Phe131) might be unstructured or flexible.
The native and functional state of MalZ was subjected to limited proteolysis by trypsin (Fig. 5a) as well as proteinase K (Fig. 5b).
The gel run after proteolysis for different time durations show a prominent band at 54 kDa, which is expected to be remaining after a truncation of about 130 amino acids. This was analysed by the molecular weight analysis program Image lab of Bio-rad.
These results confirmed that the N-terminal is getting digested during limited proteolysis. This supports our assumption that the N-terminal domain is either flexible or unstructured.
Cross-references: PDB:5BN7
Protein: DP02734 (UniProt P21517)
Region: residues 1	to 131
Annotation: disorder (Structural state)
Evidence: circular dichroism evidence used in manual assertion
Supporting statements:
The CD spectra of N-terminal hence show that although β-strands are predominant, the region is somewhat unstructured with almost half of the region showing random coil structures.
The CD spectra of MalZ N terminal domain, the secondary structure prediction suggests that almost half of the N-terminal region consists of random coil and loop regions.
The circular dichroism spectra was recorded in the range of 200–300 nm on a Jasco J-815 CD polarimeter.
Cross-references: PDB:5BN7
Protein: DP02734 (UniProt P21517)
Region: residues 419	to 430
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The density for residues 419–430 was also not observed.
Cross-references: PDB:5BN7
Protein: DP02735 (UniProt P07355)
Region: residues 2	to 33
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Annexin A2 (ANXA2) has a versatile role in membrane-associated functions including membrane aggregation, endo- and exocytosis, and it is regulated by post-translational modifications and protein-protein interactions through the unstructured N-terminal domain (NTD).
Annexins consist of a disordered N-terminal domain (NTD, ANXA2 residues 2–33) (Figure 1A) followed by a conserved C-terminal core domain (CTD, ANXA2 residues 34–339) comprising four annexin repeats
Cross-references: PDB:5LQ0
PDB:5LPX
PDB:5LQ2
Protein: DP02735 (UniProt P07355)
Region: residues 22	to 26
Annotation: phosphorylation display site (Disorder function)
Evidence: mass spectrometry evidence used in manual assertion
Supporting statements:
Phosphorylation of Tyr24 anchors the NTD to the core and inhibits membrane aggregation
In contrast, pTyr24 anchors the NTD to the CTD and hampers the membrane-bridging function.
LUV aggregation induced by wild-type ANXA2, ANXA2DNTD, ANXA2S26E, and ANXA2S12E-S26E was similar, while the amplitude of the turbidity change caused by ANXA2pY24 was 11-fold smaller than that caused by native ANXA2
Cross-references: PDB:5LQ0
PDB:5LPX
PDB:5LQ2
Protein: DP02735 (UniProt P07355)
Region: residues 2	to 33
Annotation: disorder to order (Structural transition)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
The unstructured N-terminal domain (NTD) is visible in complex with S100A4
Furthermore, it was shown that S100A4 binding requires the entire NTD
Cross-references: PDB:5LPU
Protein: DP02735 (UniProt P07355)
Region: residues 2	to 33
Annotation: protein binding (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
The unstructured N-terminal domain (NTD) is visible in complex with S100A4
Furthermore, it was shown that S100A4 binding requires the entire NTD
Cross-references: PDB:5LPU
Protein: DP02735 (UniProt P07355)
Region: residues 2	to 15
Annotation: protein binding (Molecular function)
Evidence: fluorescence polarization evidence used in manual assertion
Supporting statements:
One of the most extensively characterized properties of ANXA2 is its interaction with S100A10 forming a heterotetrameric complex (calpactin I).
To evaluate quantitatively the interaction of S100A4 with ANXA2, we performed fluorescence polarization (FP) binding studies using Fl-ANXA22−15 and Fl-ANXA22−33 fragments, as well as full-length Fl-ANXA2 variants
As expected, S100A10 bound tightly to both NTD fragments, as well as all ANXA2 constructs, with a Kd of 10–40 nM
Protein: DP02735 (UniProt P07355)
Region: residues 2	to 33
Annotation: protein binding (Molecular function)
Evidence: isothermal titration calorimetry evidence used in manual assertion
Supporting statements:
The results of the label-free isothermal titration calorimetry measurements confirmed that S100A4 binds to ANXA2 with moderate affinity (Kd ≈ 11 and 8 μM for the NTD and full-length ANXA2, respectively) and with a stoichiometry of one ANXA2 chain to an S100A4 dimer (Figures 3F and 3G).
Protein: DP02735 (UniProt P07355)
Region: residues 2	to 33
Annotation: molecular function regulator (Molecular function)
Evidence: cell aggregation evidence used in manual assertion
Supporting statements:
We also studied the effect of S100 binding and/or protein phosphorylation on ANXA2-mediated liposome aggregation. We found that Tyr24 phosphorylation reduced the conformational fluctuation of the C-NTD and it hampers the ability of ANXA2 to aggregate phosphatidylserine-containing large unilamellar vesicles (LUVs).
Modulation of ANXA2-Mediated Liposome Aggregation by Protein Phosphorylation and S100 Binding
Since we demonstrated that the pTyr24 side chain clamps the C-NTD to the CTD, a possible explanation for the tyrosine phosphorylation-mediated inhibition of LUV aggregation is that the concave side of ANXA2, which is supposedly responsible for ANXA2-ANXA2 interactions during membrane bridging, is masked by the C-NTD in the membrane-bound form as well (Figure 6B).
Protein: DP02735 (UniProt P07355)
Region: residues 2	to 33
Annotation: molecular function regulator (Molecular function)
Evidence: temperature-induced protein unfolding evidence used in manual assertion
Supporting statements:
C-NTD Phosphorylation Modulates ANXA2 Stability
Based on our crystal structures, MD simulations, and LP and DSF experiments we can conclude that the flexibility of the C-NTD and the stability of the CTD are clearly interrelated and oppositely regulated by Tyr24 phosphorylation and Ser26Glu phosphomimicking mutation.
Protein: DP02736 (UniProt Q04049)
Region: residues 510	to 528
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
There was no clear electron density beyond residue 509 indicating that this putative α helix does not have a unique position and is not part of the little finger sub-domain.
Cross-references: PDB:5VTP
Protein: DP02736 (UniProt Q04049)
Region: residues 510	to 632
Annotation: disorder (Structural state)
Evidence: small-angle X-ray scattering evidence used in manual assertion
Supporting statements:
Langevin dynamics simulations, and small-angle X-ray scattering-we show that the C-terminal region is partially unstructured and has high conformational flexibility.
Cross-references: PDB:5VTP
Protein: DP02736 (UniProt Q04049)
Region: residues 510	to 632
Annotation: molecular adaptor activity (Molecular function)
Evidence: combinatorial experimental and author inference evidence contained in single publication used in manual assertion
Supporting statements:
Langevin dynamics simulations, and small-angle X-ray scattering-we show that the C-terminal region is partially unstructured and has high conformational flexibility.
The C-terminal region mediates interactions with proliferating cell nuclear antigen (PCNA) and other translesion synthesis proteins such as Rev1. This region contains a ubiquitin-binding/zinc-binding (UBZ) motif and a PCNA-interacting protein (PIP) motif.
Cross-references: PDB:5VTP
Protein: DP02737 (UniProt Q9NWW9)
Region: residues 40	to 51
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
A region that contributes to the HRASLS2 and HRASLS3 membrane interaction is the 40–57-amino acid segment between β3 and β4
This in turn suggested an amphiphilic helix with a hydrophobic interface mainly composed of Val-50, Met-51, and Leu-54 in HRASLS3 and Val-50, Leu-51, and Leu-54 in HRASLS2 that could interact with the nonpolar core of a bilayer
Thus, the reason for the disorder observed in this particular region could stem from the lack of a proper interfacial environment in the protein crystal, as lipid membrane interactions have been shown to stabilize amphiphilic helices
The authors suggest that interaction of this region with a lipid bilayer could promote its re-folding as documented for many other amphiphilic helices, although they don't test this hypothesis
Cross-references: PDB:4DPZ
Protein: DP02737 (UniProt Q9NWW9)
Region: residues 40	to 51
Annotation: localization (Biological process)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
A region that contributes to the HRASLS2 and HRASLS3 membrane interaction is the 40–57-amino acid segment between β3 and β4
This in turn suggested an amphiphilic helix with a hydrophobic interface mainly composed of Val-50, Met-51, and Leu-54 in HRASLS3 and Val-50, Leu-51, and Leu-54 in HRASLS2 that could interact with the nonpolar core of a bilayer
Thus, the reason for the disorder observed in this particular region could stem from the lack of a proper interfacial environment in the protein crystal, as lipid membrane interactions have been shown to stabilize amphiphilic helices
The authors suggest that interaction of this region with a lipid bilayer could promote its re-folding as documented for many other amphiphilic helices, although they don't test this hypothesis
Cross-references: PDB:4DPZ
Protein: DP02738 (UniProt P08581)
Region: residues 1225	to 1244
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Electron density for the activation loop between the DFG motif and Leu-1245 is not visible in the structure, suggesting that residues 1225–1244 of the activation loop are disordered following phosphorylation.
The crystal structure of the unbound kinase domain phosphorylated at Tyr-1234 and Tyr-1235 shows that activation loop phosphorylation leads to the ejection and disorder of the activation loop and rearrangement of helix αC and the G loop to generate a viable active site.
Upon phosphorylation, the G loop adopts an extended conformation (blue) that requires ejection of the activation loop (gray) and reveals the ATP-binding site.
Cross-references: PDB:3Q6U
Protein: DP02738 (UniProt P08581)
Region: residues 1225	to 1239
Annotation: order to disorder (Structural transition)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The crystal structure of the unbound kinase domain phosphorylated at Tyr-1234 and Tyr-1235 shows that activation loop phosphorylation leads to the ejection and disorder of the activation loop and rearrangement of helix αC and the G loop to generate a viable active site.
Upon phosphorylation, the G loop adopts an extended conformation (blue) that requires ejection of the activation loop (gray) and reveals the ATP-binding site.
One of the more striking differences observed between the unbound, phosphorylated c-Met structure and the structure observed in the presence of compound 1 is the nearly complete ordering of the activation loop, including the phosphate groups of Tyr(P)-1234 and Tyr(P)-1235 (Fig. 5). Only a short region of the activation loop remains disordered (residues 1240–1243). Upon loop stabilization, the phosphotyrosine residues form electrostatic interactions: Tyr(P)-1234 interacts with Lys-1232 and Lys-1253, and Tyr(P)-1235 interacts with Arg-1227 and His-1238
Upon phosphorylation and ejection of the activation loop, the G loop adopts a remarkably different conformation that involves a movement of 9–11 Å for the Cβ atoms of Arg-1086, His-1088, and Phe-1089 (Fig. 3A). The extended β-hairpin conformation of the G loop is incompatible with the presence of the activation loop in the unphosphorylated state. This structural transition removes the active site obstruction seen in the unphosphorylated structure by the G loop side chains of Arg-1086, His-1088, and His-1089 and thus relieves an autoinhibitory feature of the unphosphorylated kinase.
Cross-references: PDB:3Q6U
PDB:3Q6W
PDB:3R7O
Protein: DP02738 (UniProt P08581)
Region: residues 1225	to 1244
Annotation: phosphorylation display site (Disorder function)
Evidence: enzymatic activity assay evidence used in manual assertion
Supporting statements:
The crystal structure of the unbound kinase domain phosphorylated at Tyr-1234 and Tyr-1235 shows that activation loop phosphorylation leads to the ejection and disorder of the activation loop and rearrangement of helix αC and the G loop to generate a viable active site.
Upon phosphorylation, the G loop adopts an extended conformation (blue) that requires ejection of the activation loop (gray) and reveals the ATP-binding site.
One of the more striking differences observed between the unbound, phosphorylated c-Met structure and the structure observed in the presence of compound 1 is the nearly complete ordering of the activation loop, including the phosphate groups of Tyr(P)-1234 and Tyr(P)-1235 (Fig. 5). Only a short region of the activation loop remains disordered (residues 1240–1243). Upon loop stabilization, the phosphotyrosine residues form electrostatic interactions: Tyr(P)-1234 interacts with Lys-1232 and Lys-1253, and Tyr(P)-1235 interacts with Arg-1227 and His-1238
Upon phosphorylation and ejection of the activation loop, the G loop adopts a remarkably different conformation that involves a movement of 9–11 Å for the Cβ atoms of Arg-1086, His-1088, and Phe-1089 (Fig. 3A). The extended β-hairpin conformation of the G loop is incompatible with the presence of the activation loop in the unphosphorylated state. This structural transition removes the active site obstruction seen in the unphosphorylated structure by the G loop side chains of Arg-1086, His-1088, and His-1089 and thus relieves an autoinhibitory feature of the unphosphorylated kinase.
Cross-references: PDB:3Q6U
PDB:3Q6W
PDB:3R7O
Protein: DP02738 (UniProt P08581)
Region: residues 1225	to 1244
Annotation: molecular function activator activity (Molecular function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The crystal structure of the unbound kinase domain phosphorylated at Tyr-1234 and Tyr-1235 shows that activation loop phosphorylation leads to the ejection and disorder of the activation loop and rearrangement of helix αC and the G loop to generate a viable active site.
Upon phosphorylation, the G loop adopts an extended conformation (blue) that requires ejection of the activation loop (gray) and reveals the ATP-binding site.
One of the more striking differences observed between the unbound, phosphorylated c-Met structure and the structure observed in the presence of compound 1 is the nearly complete ordering of the activation loop, including the phosphate groups of Tyr(P)-1234 and Tyr(P)-1235 (Fig. 5). Only a short region of the activation loop remains disordered (residues 1240–1243). Upon loop stabilization, the phosphotyrosine residues form electrostatic interactions: Tyr(P)-1234 interacts with Lys-1232 and Lys-1253, and Tyr(P)-1235 interacts with Arg-1227 and His-1238
Upon phosphorylation and ejection of the activation loop, the G loop adopts a remarkably different conformation that involves a movement of 9–11 Å for the Cβ atoms of Arg-1086, His-1088, and Phe-1089 (Fig. 3A). The extended β-hairpin conformation of the G loop is incompatible with the presence of the activation loop in the unphosphorylated state. This structural transition removes the active site obstruction seen in the unphosphorylated structure by the G loop side chains of Arg-1086, His-1088, and His-1089 and thus relieves an autoinhibitory feature of the unphosphorylated kinase.
Cross-references: PDB:3Q6U
PDB:3Q6W
PDB:3R7O
Protein: DP02739 (UniProt P45352)
Region: residues 1	to 20
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Two insertions in the rat protein are clearly seen, but the N-termini (residues 1−20) and C-termini (residues 301−307) are disordered in both crystal forms.
Both the N- and C-termini were disordered in the first rTS structure, and residues r1−r20 and r301−r307 were therefore left out of the final model.
Cross-references: PDB:1RTS
PDB:2TSR
Protein: DP02740 (UniProt P08179)
Region: residues 110	to 132
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The structure is a modified doubly wound alpha/beta sheet with flexibility in the active site, including a disordered loop in the apo structure, which is ordered in the ternary complex structure.
The apo models include all protein atoms for residues 1-109 and 133-212, whereas the ternary model includes residues 1-209.
Cross-references: PDB:1CDD
Protein: DP02740 (UniProt P08179)
Region: residues 110	to 132
Annotation: disorder to order (Structural transition)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The structure is a modified doubly wound alpha/beta sheet with flexibility in the active site, including a disordered loop in the apo structure, which is ordered in the ternary complex structure.
The apo models include all protein atoms for residues 1-109 and 133-212, whereas the ternary model includes residues 1-209.
The disordered loop at position 110-132 in the apo structure (PDB:1CDD) becomes ordered in the ternary complex structure with the substrate glycinamide ribonucleotide and a folate inhibitor (PDB:1CDE)
Cross-references: PDB:1CDD
PDB:1CDE
Protein: DP02741 (UniProt P09951)
Region: residues 2	to 111
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The evidence supports a view of synapsin I as an ATP-utilizing, tetrameric protein made up of monomers that have a flexible, extended N terminus.
Cross-references: PDB:1PX2
PDB:1PK8
Protein: DP02741 (UniProt P09951)
Region: residues 7	to 11
Annotation: phosphorylation display site (Disorder function)
Evidence: sodium dodecyl sulfate polyacrylamide gel electrophoresis evidence used in manual assertion
Supporting statements:
Only two domains are conserved in all synapsins: a short N-terminal A domain with a single phosphorylation site for cAMP-dependent protein kinase (PKA) and CaM Kinase I, and a large central C domain that binds ATP and may be enzymatic. We now demonstrate that synapsin phosphorylation in the A domain, at the only phosphorylation site shared by all synapsins, dissociates synapsins from synaptic vesicles. Furthermore, we show that the A domain binds phospholipids and is inhibited by phosphorylation. Our results suggest a novel mechanism by which proteins reversibly bind to membranes using a phosphorylation-dependent phospholipid-binding domain. The dynamic association of synapsins with synaptic vesicles correlates with their role in activity-dependent plasticity.
The phosphorylated site corresponds to Ser9 of Synaptin I.