LiteFold/DisProt huggingface dataset:
Protein: DP00157 (UniProt P0CL52)
Region: residues 426	to 513
Annotation: disorder (Structural state)
Evidence: cleavage assay evidence used in manual assertion
Supporting statements:
To further probe this hypothesis of flexible polypeptides at the N- and C-termini of the molecule, we subjected a larger construct, SipA425–684, to limited proteolysis with the relatively nonspecific protease subtilisin (Fig. 3E) (11). The protease cut very effectively until it approached a construct that was ordered in the crystals (SipA513–657), producing trimmed constructs that when subcloned and overexpressed were highly soluble, stable, and active to bind F-actin (Fig. 3, E and F).
Protein: DP00157 (UniProt P0CL52)
Region: residues 659	to 685
Annotation: disorder (Structural state)
Evidence: cleavage assay evidence used in manual assertion
Supporting statements:
To further probe this hypothesis of flexible polypeptides at the N- and C-termini of the molecule, we subjected a larger construct, SipA425–684, to limited proteolysis with the relatively nonspecific protease subtilisin (Fig. 3E) (11). The protease cut very effectively until it approached a construct that was ordered in the crystals (SipA513–657), producing trimmed constructs that when subcloned and overexpressed were highly soluble, stable, and active to bind F-actin (Fig. 3, E and F).
Protein: DP00157 (UniProt P0CL52)
Region: residues 426	to 513
Annotation: disorder (Structural state)
Evidence: small-angle X-ray scattering evidence used in manual assertion
Supporting statements:
We determined the hydrodynamic radius of various SipA constructs (Fig. 3F) and found not only that the ordered core (as found in the crystals) was globular in solution but also that SipA constructs with additional polypeptide arms were elongated in solution and became increasingly elongated as more arm polypeptide was added (Fig. 3F).
Protein: DP00157 (UniProt P0CL52)
Region: residues 659	to 685
Annotation: disorder (Structural state)
Evidence: small-angle X-ray scattering evidence used in manual assertion
Supporting statements:
We determined the hydrodynamic radius of various SipA constructs (Fig. 3F) and found not only that the ordered core (as found in the crystals) was globular in solution but also that SipA constructs with additional polypeptide arms were elongated in solution and became increasingly elongated as more arm polypeptide was added (Fig. 3F).
Protein: DP00157 (UniProt P0CL52)
Region: residues 229	to 242
Annotation: disorder (Structural state)
Evidence: crystallography evidence used in manual assertion
Supporting statements:
Two N-terminal helices pack more loosely against this core fold, forming a small subdomain that extends into solution (protrusion) with the last ten amino acids as a random coil that is characterized by partial disorder and high temperature factors (Figure 1B).
(B) The overall fold of SipA48–264 drawn as a ribbon diagram with secondary structure elements and NH2-terminal protrusion labeled. Regions disordered in the crystal structure are shown as dotted lines connecting the appropriate regions of secondary structure.
Cross-references: PDB:2FM9
Protein: DP00159 (UniProt P09803)
Region: residues 812	to 884
Annotation: molecular adaptor activity (Molecular function)
Evidence: experimental evidence used in manual assertion
Supporting statements:
Cadherins are single pass transmembrane proteins that mediate Ca(2+)-dependent homophilic cell-cell adhesion by linking the cytoskeletons of adjacent cells. In adherens junctions, the cytoplasmic domain of cadherins bind to beta-catenin, which in turn binds to the actin-associated protein alpha-catenin.
Protein: DP00159 (UniProt P09803)
Region: residues 812	to 884
Annotation: disorder to order (Structural transition)
Evidence: experimental evidence used in manual assertion
Supporting statements:
Our analysis shows that the cadherin cytoplasmic tail is unstructured in isolation but appears to become structured upon binding to β-catenin.
Protein: DP00159 (UniProt P09803)
Region: residues 812	to 884
Annotation: protein binding (Molecular function)
Evidence: experimental evidence used in manual assertion
Supporting statements:
The physical properties of the E-cadherin cytoplasmic domain and its interactions with beta-catenin have been investigated. Proteolytic sensitivity, tryptophan fluorescence, circular dichroism, and (1)H NMR measurements indicate that murine E-cadherin cytoplasmic domain is unstructured. Upon binding to beta-catenin, the domain becomes resistant to proteolysis, suggesting that it structures upon binding. Cadherin-beta-catenin complex stability is modestly dependent on ionic strength, indicating that, contrary to previous proposals, the interaction is not dominated by electrostatics.
Protein: DP00159 (UniProt P09803)
Region: residues 812	to 884
Annotation: molecular adaptor activity (Molecular function)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
Cadherins are single pass transmembrane proteins that mediate Ca(2+)-dependent homophilic cell-cell adhesion by linking the cytoskeletons of adjacent cells. In adherens junctions, the cytoplasmic domain of cadherins bind to beta-catenin, which in turn binds to the actin-associated protein alpha-catenin.
Protein: DP00159 (UniProt P09803)
Region: residues 812	to 884
Annotation: disorder to order (Structural transition)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
Our analysis shows that the cadherin cytoplasmic tail is unstructured in isolation but appears to become structured upon binding to β-catenin.
Protein: DP00159 (UniProt P09803)
Region: residues 812	to 884
Annotation: protein binding (Molecular function)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
The physical properties of the E-cadherin cytoplasmic domain and its interactions with beta-catenin have been investigated. Proteolytic sensitivity, tryptophan fluorescence, circular dichroism, and (1)H NMR measurements indicate that murine E-cadherin cytoplasmic domain is unstructured. Upon binding to beta-catenin, the domain becomes resistant to proteolysis, suggesting that it structures upon binding. Cadherin-beta-catenin complex stability is modestly dependent on ionic strength, indicating that, contrary to previous proposals, the interaction is not dominated by electrostatics.
Protein: DP00159 (UniProt P09803)
Region: residues 812	to 884
Annotation: molecular adaptor activity (Molecular function)
Evidence: cleavage assay evidence used in manual assertion
Supporting statements:
Cadherins are single pass transmembrane proteins that mediate Ca(2+)-dependent homophilic cell-cell adhesion by linking the cytoskeletons of adjacent cells. In adherens junctions, the cytoplasmic domain of cadherins bind to beta-catenin, which in turn binds to the actin-associated protein alpha-catenin.
Protein: DP00159 (UniProt P09803)
Region: residues 812	to 884
Annotation: disorder to order (Structural transition)
Evidence: cleavage assay evidence used in manual assertion
Supporting statements:
Our analysis shows that the cadherin cytoplasmic tail is unstructured in isolation but appears to become structured upon binding to β-catenin.
Protein: DP00159 (UniProt P09803)
Region: residues 812	to 884
Annotation: protein binding (Molecular function)
Evidence: cleavage assay evidence used in manual assertion
Supporting statements:
The physical properties of the E-cadherin cytoplasmic domain and its interactions with beta-catenin have been investigated. Proteolytic sensitivity, tryptophan fluorescence, circular dichroism, and (1)H NMR measurements indicate that murine E-cadherin cytoplasmic domain is unstructured. Upon binding to beta-catenin, the domain becomes resistant to proteolysis, suggesting that it structures upon binding. Cadherin-beta-catenin complex stability is modestly dependent on ionic strength, indicating that, contrary to previous proposals, the interaction is not dominated by electrostatics.
Protein: DP00159 (UniProt P09803)
Region: residues 812	to 884
Annotation: molecular adaptor activity (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Cadherins are single pass transmembrane proteins that mediate Ca(2+)-dependent homophilic cell-cell adhesion by linking the cytoskeletons of adjacent cells. In adherens junctions, the cytoplasmic domain of cadherins bind to beta-catenin, which in turn binds to the actin-associated protein alpha-catenin.
Protein: DP00159 (UniProt P09803)
Region: residues 812	to 884
Annotation: disorder to order (Structural transition)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Our analysis shows that the cadherin cytoplasmic tail is unstructured in isolation but appears to become structured upon binding to β-catenin.
Protein: DP00159 (UniProt P09803)
Region: residues 812	to 884
Annotation: protein binding (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The physical properties of the E-cadherin cytoplasmic domain and its interactions with beta-catenin have been investigated. Proteolytic sensitivity, tryptophan fluorescence, circular dichroism, and (1)H NMR measurements indicate that murine E-cadherin cytoplasmic domain is unstructured. Upon binding to beta-catenin, the domain becomes resistant to proteolysis, suggesting that it structures upon binding. Cadherin-beta-catenin complex stability is modestly dependent on ionic strength, indicating that, contrary to previous proposals, the interaction is not dominated by electrostatics.
Protein: DP00159 (UniProt P09803)
Region: residues 732	to 884
Annotation: protein binding (Molecular function)
Evidence: isothermal titration calorimetry evidence used in manual assertion
Supporting statements:
Plakoglobin binds to the full 152-amino acid cytoplasmic domain of E-cadherin (Ecyto) with a dissociation constant KD of 85 nm.
Cross-references: PDB:3IFQ
Protein: DP00159 (UniProt P09803)
Region: residues 778	to 884
Annotation: protein binding (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
Here, we report structural, biophysical, and biochemical studies aimed at understanding the molecular basis of selective exclusion of β-catenin and α-catenin from desmosomes. The crystal structure of the plakoglobin armadillo domain bound to phosphorylated E-cadherin shows virtually identical interactions to those observed between β-catenin and E-cadherin.
Cross-references: PDB:3IFQ
Protein: DP00159 (UniProt P09803)
Region: residues 784	to 852
Annotation: disorder to order (Structural transition)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
Here, we report structural, biophysical, and biochemical studies aimed at understanding the molecular basis of selective exclusion of β-catenin and α-catenin from desmosomes. The crystal structure of the plakoglobin armadillo domain bound to phosphorylated E-cadherin shows virtually identical interactions to those observed between β-catenin and E-cadherin.
Cross-references: PDB:3IFQ
Protein: DP00159 (UniProt P09803)
Region: residues 855	to 881
Annotation: disorder to order (Structural transition)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
Here, we report structural, biophysical, and biochemical studies aimed at understanding the molecular basis of selective exclusion of β-catenin and α-catenin from desmosomes. The crystal structure of the plakoglobin armadillo domain bound to phosphorylated E-cadherin shows virtually identical interactions to those observed between β-catenin and E-cadherin.
Cross-references: PDB:3IFQ
Protein: DP00159 (UniProt P09803)
Region: residues 778	to 884
Annotation: phosphorylation display site (Disorder function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
Here, we report structural, biophysical, and biochemical studies aimed at understanding the molecular basis of selective exclusion of β-catenin and α-catenin from desmosomes. The crystal structure of the plakoglobin armadillo domain bound to phosphorylated E-cadherin shows virtually identical interactions to those observed between β-catenin and E-cadherin.
Phosphorylated residues are Ser840, Ser 842 and Ser848.
Cross-references: PDB:3IFQ
Protein: DP00159 (UniProt P09803)
Region: residues 736	to 884
Annotation: disorder (Structural state)
Evidence: experimental evidence used in manual assertion
Supporting statements:
Proteolytic sensitivity, tryptophan fluorescence, circular dichroism, and (1)H NMR measurements indicate that murine E-cadherin cytoplasmic domain is unstructured. Upon binding to beta-catenin, the domain becomes resistant to proteolysis, suggesting that it structures upon binding.
The fluoresence anisotropy data suggest that the Ecyto and DEcyto domains are unfolded under native conditions.
The cytoplasmic tail is the most highly conserved domain among type I cadherins (34). With a length of ∼150 residues, it is easily large enough to be an independently folded structural unit. We expressed the E- and DE-cadherin cytoplasmic domains in E. coli and purified them to homogeneity. Tryptophan fluorescence, circular dichroism, and one-dimensional proton NMR studies all lead to the same surprising conclusion: rEcyto and rDEcyto are unfolded in solution.
Protein: DP00159 (UniProt P09803)
Region: residues 736	to 884
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
Proteolytic sensitivity, tryptophan fluorescence, circular dichroism, and (1)H NMR measurements indicate that murine E-cadherin cytoplasmic domain is unstructured. Upon binding to beta-catenin, the domain becomes resistant to proteolysis, suggesting that it structures upon binding.
CD spectroscopy was therefore used to probe for the presence regular protein secondary structure. The spectra measured for rEcyto and rDEcyto at 0 °C are essentially identical and feature a single minimum in mean residue ellipticity at ∼202 nm (Fig. 1). This spectrum indicates a lack of secondary structure, which would be expected of an unstructured polypeptide. 
The cytoplasmic tail is the most highly conserved domain among type I cadherins (34). With a length of ∼150 residues, it is easily large enough to be an independently folded structural unit. We expressed the E- and DE-cadherin cytoplasmic domains in E. coli and purified them to homogeneity. Tryptophan fluorescence, circular dichroism, and one-dimensional proton NMR studies all lead to the same surprising conclusion: rEcyto and rDEcyto are unfolded in solution.
Protein: DP00159 (UniProt P09803)
Region: residues 736	to 884
Annotation: disorder (Structural state)
Evidence: cleavage assay evidence used in manual assertion
Supporting statements:
Proteolytic sensitivity, tryptophan fluorescence, circular dichroism, and (1)H NMR measurements indicate that murine E-cadherin cytoplasmic domain is unstructured. Upon binding to beta-catenin, the domain becomes resistant to proteolysis, suggesting that it structures upon binding.
β-Catenin Binding Protects Ecyto from Proteolysis.
The cytoplasmic tail is the most highly conserved domain among type I cadherins (34). With a length of ∼150 residues, it is easily large enough to be an independently folded structural unit. We expressed the E- and DE-cadherin cytoplasmic domains in E. coli and purified them to homogeneity. Tryptophan fluorescence, circular dichroism, and one-dimensional proton NMR studies all lead to the same surprising conclusion: rEcyto and rDEcyto are unfolded in solution.
Protein: DP00159 (UniProt P09803)
Region: residues 736	to 884
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Proteolytic sensitivity, tryptophan fluorescence, circular dichroism, and (1)H NMR measurements indicate that murine E-cadherin cytoplasmic domain is unstructured. Upon binding to beta-catenin, the domain becomes resistant to proteolysis, suggesting that it structures upon binding.
The cytoplasmic tail is the most highly conserved domain among type I cadherins (34). With a length of ∼150 residues, it is easily large enough to be an independently folded structural unit. We expressed the E- and DE-cadherin cytoplasmic domains in E. coli and purified them to homogeneity. Tryptophan fluorescence, circular dichroism, and one-dimensional proton NMR studies all lead to the same surprising conclusion: rEcyto and rDEcyto are unfolded in solution.
Protein: DP00159 (UniProt P09803)
Region: residues 812	to 884
Annotation: molecular function regulator (Molecular function)
Evidence: experimental evidence used in manual assertion
Supporting statements:
It is proposed that binding of cadherins to beta-catenin prevents recognition of degradation signals that are exposed in the unstructured cadherin cytoplasmic domain, favoring a cell surface population of catenin-bound cadherins capable of participating in cell adhesion.
Protein: DP00159 (UniProt P09803)
Region: residues 812	to 884
Annotation: molecular function regulator (Molecular function)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
It is proposed that binding of cadherins to beta-catenin prevents recognition of degradation signals that are exposed in the unstructured cadherin cytoplasmic domain, favoring a cell surface population of catenin-bound cadherins capable of participating in cell adhesion.
Protein: DP00159 (UniProt P09803)
Region: residues 812	to 884
Annotation: molecular function regulator (Molecular function)
Evidence: cleavage assay evidence used in manual assertion
Supporting statements:
It is proposed that binding of cadherins to beta-catenin prevents recognition of degradation signals that are exposed in the unstructured cadherin cytoplasmic domain, favoring a cell surface population of catenin-bound cadherins capable of participating in cell adhesion.
Protein: DP00159 (UniProt P09803)
Region: residues 812	to 884
Annotation: molecular function regulator (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
It is proposed that binding of cadherins to beta-catenin prevents recognition of degradation signals that are exposed in the unstructured cadherin cytoplasmic domain, favoring a cell surface population of catenin-bound cadherins capable of participating in cell adhesion.
Protein: DP00159 (UniProt P09803)
Region: residues 736	to 884
Annotation: protein binding (Molecular function)
Evidence: chromatography evidence used in manual assertion
Supporting statements:
Mixtures of rEcyto or rDEcyto and various β-catenin constructs were incubated for more than 1 h at 4 °C and injected onto an Amersham Pharmacia Biotech HR 10/30 Superdex 200 size exclusion column equilibrated with 50 mm Tris-HCl, pH 8, 200 mm NaCl, 20 mm EDTA, and 1 mmDTT.
Protein: DP00161 (UniProt P77173)
Region: residues 29	to 185
Annotation: disorder (Structural state)
Evidence: rotary shadowing electron microscopy evidence used in manual assertion
Supporting statements:
Occasionally, a very small globular particle or a thin extension could be seen close to the main globular particle but, for the most part, there was no visible structure corresponding to the charged and P/Q domains in ZipA(23-328). This suggested that the P/Q domain may be a largely unfolded polypeptide and invisible in the rotary shadowed specimen, consistent with the previous prediction from the sequence (3). We suggest that the charged domain may be unstructured as well because, in our experience, a 60-aa globular domain should be visible in rotary shadowing.
Protein: DP00161 (UniProt P77173)
Region: residues 29	to 185
Annotation: flexible linker (Disorder function)
Evidence: rotary shadowing electron microscopy evidence used in manual assertion
Supporting statements:
Occasionally, a very small globular particle or a thin extension could be seen close to the main globular particle but, for the most part, there was no visible structure corresponding to the charged and P/Q domains in ZipA(23-328). This suggested that the P/Q domain may be a largely unfolded polypeptide and invisible in the rotary shadowed specimen, consistent with the previous prediction from the sequence (3). We suggest that the charged domain may be unstructured as well because, in our experience, a 60-aa globular domain should be visible in rotary shadowing.
We propose, on the basis of our EM analyses, that the tether is flexible and can span a maximum distance of 60 nm.
Protein: DP00162 (UniProt O75324)
Region: residues 34	to 60
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The structure is composed of a single transmembrane helix from residues 10–33, a large dynamic unstructured linker region, and a distorted cytoplasmic helix from residues 61–79 that interacts with the surface of the lipid bilayer.
Cross-references: PDB:1ZZA
Protein: DP00162 (UniProt O75324)
Region: residues 34	to 60
Annotation: flexible linker (Disorder function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The structure is composed of a single transmembrane helix from residues 10–33, a large dynamic unstructured linker region, and a distorted cytoplasmic helix from residues 61–79 that interacts with the surface of the lipid bilayer.
Another distinguishing feature that separates SNN from the structures of the aforementioned proteins is that the two helical domains of SNN are connected by a rather long unstructured linker.
Cross-references: PDB:1ZZA
Protein: DP00163 (UniProt Q03768)
Region: residues 1	to 166
Annotation: disorder (Structural state)
Evidence: sodium dodecyl sulfate polyacrylamide gel electrophoresis evidence used in manual assertion
Supporting statements:
Significantly, the N-terminal half containing residues 1–166 migrated with more than double the expected mass, thus surpassing the complete protein in the ratio expected/observed mass. These results clearly indicated that the amino-terminal half of Gir2 is responsible for the characteristic abnormal migration of Gir2 on SDS–PAGE.
Protein: DP00163 (UniProt Q03768)
Region: residues 1	to 265
Annotation: disorder (Structural state)
Evidence: in vitro cleavage assay evidence used in manual assertion
Supporting statements:
As shown in Fig. 1 (upper panel), Gir2 is extremely sensitive to proteolysis when compared to GST in the conditions used here. At 1:100 ratio of enzyme/substrate, Gir2 is readily degraded whereas GST is intact. Remarkably, even when using the lowest amount of enzyme (1:4000), proteolysis of Gir2 is readily detected.
Protein: DP00163 (UniProt Q03768)
Region: residues 1	to 166
Annotation: disorder (Structural state)
Evidence: in vitro cleavage assay evidence used in manual assertion
Supporting statements:
 We also employed in these assays a truncated Gir2 protein comprising residues 1–166. His6–Gir2[1–166] seemed to be more sensitive to proteolysis than the complete protein, when the assays are normalized by the molar ratio of enzyme/substrate (Fig. 1, lower panel)
Protein: DP00163 (UniProt Q03768)
Region: residues 1	to 265
Annotation: pre-molten globule (Structural state)
Evidence: gel-filtration evidence used in manual assertion
Supporting statements:
The similarity between the predicted Rs by gel filtration experiments (3.23 nm for His6-Gir2[1–265] and 3.18 nm for His6-Gir2[1–166]) and that predicted from conformational class (3.67 nm for His6-Gir2[1–265] and 3.21 nm for His6-Gir2[1–166]) suggests that this protein is a pre-molten globule (PMG).