LiteFold/DisProt huggingface dataset:
Protein: DP00262 (UniProt Q16665)
Region: residues 776	to 826
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Hif-1α (776–826) in the unbound state is intrinsically disordered; its circular dichroism spectrum is characteristic of a random coil (data not shown) and the NMR spectrum lacks dispersion (Fig.1, red cross peaks).
Protein: DP00262 (UniProt Q16665)
Region: residues 403	to 603
Annotation: disorder (Structural state)
Evidence: analytical ultracentrifugation evidence used in manual assertion
Supporting statements:
Analysis of the sedimentation equilibrium centrifugation experiment, however, showed that both proteins were monomeric with a Mr of 18,000 ± 120 and 22,000 ± 500 (Figure 1B; as an example for HIF-1α 530–698).
These results imply that both HIF-1α 530–698 and HIF-1α 403–603 have the dimensions of denatured proteins and have extended conformations.
Protein: DP00262 (UniProt Q16665)
Region: residues 791	to 804
Annotation: disorder to order (Structural transition)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The CAD becomes structured upon binding to TAZ1, as evidenced by the pronounced increase in dispersion of the amide proton resonances (Fig.1, black cross peaks).
The structure of the bound Hif-1α CAD is better defined after Gly-791.
The extended region of the Hif-1α CAD leads directly into a short α-helix (residues 796–804), termed αB, which docks in a groove formed by the N-terminal end of α1, helix α3, and the Zn3 site of TAZ1 (Fig.2B). Another helix, αC, is formed by residues 815–824. Helices αB and αC lie on opposite sides of helix α3 of TAZ1 (Fig.2B); residues 804–813 form an irregular bridge over α3 and make numerous contacts with the surface of TAZ1. In particular, the conserved leucines at positions 812 and 813 (Fig.4A) together with Ile-806 form a shallow hydrophobic groove that fits over two turns of helix α3 (Fig.4D).
Cross-references: BMRB:5327
PDB:1L8C
Protein: DP00262 (UniProt Q16665)
Region: residues 815	to 824
Annotation: disorder to order (Structural transition)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The CAD becomes structured upon binding to TAZ1, as evidenced by the pronounced increase in dispersion of the amide proton resonances (Fig.1, black cross peaks).
The structure of the bound Hif-1α CAD is better defined after Gly-791.
The extended region of the Hif-1α CAD leads directly into a short α-helix (residues 796–804), termed αB, which docks in a groove formed by the N-terminal end of α1, helix α3, and the Zn3 site of TAZ1 (Fig.2B). Another helix, αC, is formed by residues 815–824. Helices αB and αC lie on opposite sides of helix α3 of TAZ1 (Fig.2B); residues 804–813 form an irregular bridge over α3 and make numerous contacts with the surface of TAZ1. In particular, the conserved leucines at positions 812 and 813 (Fig.4A) together with Ile-806 form a shallow hydrophobic groove that fits over two turns of helix α3 (Fig.4D).
Cross-references: BMRB:5327
PDB:1L8C
Protein: DP00262 (UniProt Q16665)
Region: residues 776	to 826
Annotation: protein binding (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The CAD becomes structured upon binding to TAZ1, as evidenced by the pronounced increase in dispersion of the amide proton resonances (Fig.1, black cross peaks).
Residues 776–790 in the N-terminal region of the Hif-1α CAD are poorly defined in the structures. Nevertheless, intermolecular NOEs are observed which show that this region of the CAD does bind, albeit weakly, in a broad shallow groove formed by helices α1 and α4 of TAZ1.
The extended region of the Hif-1α CAD leads directly into a short α-helix (residues 796–804), termed αB, which docks in a groove formed by the N-terminal end of α1, helix α3, and the Zn3 site of TAZ1 (Fig.2B). Another helix, αC, is formed by residues 815–824. Helices αB and αC lie on opposite sides of helix α3 of TAZ1 (Fig.2B); residues 804–813 form an irregular bridge over α3 and make numerous contacts with the surface of TAZ1. In particular, the conserved leucines at positions 812 and 813 (Fig.4A) together with Ile-806 form a shallow hydrophobic groove that fits over two turns of helix α3 (Fig.4D).
Cross-references: BMRB:5327
PDB:1L8C
Protein: DP00262 (UniProt Q16665)
Region: residues 776	to 826
Annotation: protein binding (Molecular function)
Evidence: yeast 2-hybrid evidence used in manual assertion
Supporting statements:
Yeast two-hybrid assays confirmed that the constructs used for the NMR experiments, HIF-1α (776–826) and TAZ1 (345–439), interact specifically and with high affinity in vivo.
Protein: DP00262 (UniProt Q16665)
Region: residues 776	to 826
Annotation: protein binding (Molecular function)
Evidence: isothermal titration calorimetry evidence used in manual assertion
Supporting statements:
The dissociation constant of the TAZ1/HIF-1α CAD complex was determined to be 7 ± 1 nM by ITC.
Protein: DP00262 (UniProt Q16665)
Region: residues 530	to 698
Annotation: disorder (Structural state)
Evidence: sodium dodecyl sulfate polyacrylamide gel electrophoresis evidence used in manual assertion
Supporting statements:
In addition, HIF-1α 530–698 and HIF-1α 403–603 both migrated as a 32 kDa protein in an SDS-PAGE gel even after heat denaturation (Figure 1A, inset).
These results imply that both HIF-1α 530–698 and HIF-1α 403–603 have the dimensions of denatured proteins and have extended conformations.
Protein: DP00262 (UniProt Q16665)
Region: residues 403	to 603
Annotation: disorder (Structural state)
Evidence: sodium dodecyl sulfate polyacrylamide gel electrophoresis evidence used in manual assertion
Supporting statements:
In addition, HIF-1α 530–698 and HIF-1α 403–603 both migrated as a 32 kDa protein in an SDS-PAGE gel even after heat denaturation (Figure 1A, inset).
These results imply that both HIF-1α 530–698 and HIF-1α 403–603 have the dimensions of denatured proteins and have extended conformations.
Protein: DP00262 (UniProt Q16665)
Region: residues 403	to 603
Annotation: p53 binding (Molecular function)
Evidence: fluorescence anisotropy evidence used in manual assertion
Supporting statements:
In contrast with HIF-1α 530–698, at the highest ionic strength (I 200 mM) it was possible to detect weak binding (Kd 600 μM) between HIF-1α 403–603 and p53 core, while at I 150 mM the binding was slightly tighter, Kd 200 μM.
Protein: DP00262 (UniProt Q16665)
Region: residues 403	to 603
Annotation: p53 binding (Molecular function)
Evidence: analytical ultracentrifugation evidence used in manual assertion
Supporting statements:
In both cases, however, the AUC data described species of 23 ± 1.2 and 48 ± 1 kDa, suggesting that even when the HIF-1α 403–603 construct contains the two binding sites predicted by Hansson et al. (2002), the stoichiometry of the complex is 1:1 (Figures 4C and 4D).
Protein: DP00262 (UniProt Q16665)
Region: residues 530	to 698
Annotation: p53 binding (Molecular function)
Evidence: analytical ultracentrifugation evidence used in manual assertion
Supporting statements:
For HIF-1α 530–698, at an ionic strength of 200 mM, no binding was detected, and the data best described a single species of Mr 21,000, corresponding to HIF-1α 530–698 alone. At physiological ionic strength (I 150 mM), the interaction was very weak (Kd 690 μM).
Protein: DP00262 (UniProt Q16665)
Region: residues 530	to 698
Annotation: p53 binding (Molecular function)
Evidence: fluorescence anisotropy evidence used in manual assertion
Supporting statements:
Using fluorescence anisotropy (Figures 5A and 5B), at lower ionic strengths the binding was tighter, with dissociation constants 30 and 0.16 μM at I 56 and 20 mM. respectively.
Protein: DP00262 (UniProt Q16665)
Region: residues 776	to 813
Annotation: protein binding (Molecular function)
Evidence: fluorescence evidence used in manual assertion
Supporting statements:
Although the residues 776–790 of HIF-1α, were implicated to interact, albeit weakly, with CBP [17], the two peptides showed similar binding affinities, with the dissociation constants of 196 ± 39 nM for F-HIF-1α-(776–786) and of 198 ± 23 nM for F-HIF-1α-(786–826). On the other hand, FP of F-HIF-1α-(788–822) increased much less, while F-HIF-1α-(776–813) showed no FP increase up to 3 μM GST-CBP (Fig. 2A).
Cross-references: IntAct:EBI-7354842
Protein: DP00262 (UniProt Q16665)
Region: residues 795	to 822
Annotation: transcription regulator activator activity (Molecular function)
Evidence: GAL4-VP16 functional complementation evidence used in manual assertion
Supporting statements:
These results confirm that the residues identified by RAMSY are functionally critical for CAD transcriptional activity in mammalian cells.
Therefore, we conclude that Leu-795, Cys-800, Leu-818, and Leu-822 of HIF1a are functionally indispensable for CAD transcriptional activity in mammalian cells.
Protein: DP00262 (UniProt Q16665)
Region: residues 560	to 567
Annotation: ubiquitin protein ligase binding (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
In contrast, recognition of HIF-1α by VCB E3 ligase (pVHL, elongins B and C, Cul2 and Rbx1; ref. 10) requires hydroxylation of specific prolyl residues by a group of 2-oxoglutarate-dependent, non-haem dioxygenases11,12.
Electron density for HIF-1α peptide residues 560–577 is of good quality, with only the side chain of E560 poorly defined (Fig. 1). The peptide lies in an extended conformation across one side of the β-domain of pVHL (Fig. 2a, b), binding to one of the β-sheets as if it were a complementary β-strand, although there is no extensive main-chain hydrogen bonding to define it as such.
Within the CODD peptide, residues 560–567 and 571–577 form distinct binding sites (sites 1 and 2, respectively).
Site 1 (EMLAHypYIP) is the primary binding site, contributing more than 60% of the total buried surface area and van der Waals contacts.
Cross-references: PDB:1LQB
ELM:DEG_ODPH_VHL_1
Protein: DP00262 (UniProt Q16665)
Region: residues 556	to 574
Annotation: ubiquitin protein ligase binding (Molecular function)
Evidence: surface plasmon resonance evidence used in manual assertion
Supporting statements:
In contrast, recognition of HIF-1α by VCB E3 ligase (pVHL, elongins B and C, Cul2 and Rbx1; ref. 10) requires hydroxylation of specific prolyl residues by a group of 2-oxoglutarate-dependent, non-haem dioxygenases11,12.
Hydroxylated human CODD and NODD, and C. elegans ODD peptides, bind VCB with similar kinetics and binding affinities (29–53 nM).
Protein: DP00262 (UniProt Q16665)
Region: residues 561	to 566
Annotation: ubiquitin protein ligase binding (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
It binds pVHL in a bipartite manner, with two discontinuous HIF-1α segments interacting with a continuous site on pVHL. A six-residue NH2-terminal segment (residues 561 to 566; N segment) that is centered on Hyp564 (Hyp is the three-letter code for hydroxyproline), and a four-residue COOH-terminal segment (residues 571 to 574; C segment) are separated by a four–amino acid bulge that does not contact pVHL (Fig. 1B).
A 20-residue HIF-1α ODD region (destruction sequence), conserved in animal orthologs and paralogs, is necessary and sufficient for hydroxylation by HPHs and for binding to pVHL (12, 13).
pVHL is the substrate-recognition subunit of a ubiquitin-protein ligase that also contains ElonginB, ElonginC, Cul2, and Rbx1 (VBC-CR complex) (6–9).
The VBC complex is a E3 ubiquitin ligase.
Cross-references: PDB:1LM8
ELM:DEG_ODPH_VHL_1
Protein: DP00262 (UniProt Q16665)
Region: residues 571	to 574
Annotation: ubiquitin protein ligase binding (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
It binds pVHL in a bipartite manner, with two discontinuous HIF-1α segments interacting with a continuous site on pVHL. A six-residue NH2-terminal segment (residues 561 to 566; N segment) that is centered on Hyp564 (Hyp is the three-letter code for hydroxyproline), and a four-residue COOH-terminal segment (residues 571 to 574; C segment) are separated by a four–amino acid bulge that does not contact pVHL (Fig. 1B).
A 20-residue HIF-1α ODD region (destruction sequence), conserved in animal orthologs and paralogs, is necessary and sufficient for hydroxylation by HPHs and for binding to pVHL (12, 13).
pVHL is the substrate-recognition subunit of a ubiquitin-protein ligase that also contains ElonginB, ElonginC, Cul2, and Rbx1 (VBC-CR complex) (6–9).
The VBC complex is a E3 ubiquitin ligase.
Cross-references: PDB:1LM8
ELM:DEG_ODPH_VHL_1
Protein: DP00262 (UniProt Q16665)
Region: residues 571	to 577
Annotation: ubiquitin protein ligase binding (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
In contrast, recognition of HIF-1α by VCB E3 ligase (pVHL, elongins B and C, Cul2 and Rbx1; ref. 10) requires hydroxylation of specific prolyl residues by a group of 2-oxoglutarate-dependent, non-haem dioxygenases11,12.
Electron density for HIF-1α peptide residues 560–577 is of good quality, with only the side chain of E560 poorly defined (Fig. 1). The peptide lies in an extended conformation across one side of the β-domain of pVHL (Fig. 2a, b), binding to one of the β-sheets as if it were a complementary β-strand, although there is no extensive main-chain hydrogen bonding to define it as such.
Within the CODD peptide, residues 560–567 and 571–577 form distinct binding sites (sites 1 and 2, respectively).
Cross-references: PDB:1LQB
ELM:DEG_ODPH_VHL_1
Protein: DP00265 (UniProt P04925)
Region: residues 23	to 120
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The recombinant murine prion protein, mPrP(23-231), was expressed in E. coli with uniform 15N-labeling. NMR experiments showed that the previously determined globular three-dimensional structure of the C-terminal domain mPrP(121-231) is preserved in the intact protein, and that the N-terminal polypeptide segment 23-120 is flexibly disordered.
Dots represent the 98 residues of the N-terminal segment 23-120, which shows features of a flexible, 'random coil-like' polypeptide, with rotational correlation times for the ''N-'H groups of τc < 1 ns.
The N-terminal polypeptide segment 23-120 has a small dispersion of the proton chemical shifts and τc-values <1 ns for the 15N-1H moieties, which is typical for a flexible 'random coil-like' polypeptide chain.
Protein: DP00265 (UniProt P04925)
Region: residues 105	to 119
Annotation: protein binding (Molecular function)
Evidence: deletion mutation phenotypic evidence used in manual assertion
Supporting statements:
We report that PrP(C) interacts with vitronectin but not with fibronectin or collagen. The binding sites mediating this PrP(C)-vitronectin interaction were mapped to residues 105-119 of PrP(C) and the residues 307-320 of vitronectin.
Of the twenty peptides from mouse PrPC covering the whole protein sequence used to compete for PrPC-Vn binding, two of them, corresponding to PrPC residues 103-122 and 113-132, effectively blocked (by ∼80%) PrPC-Vn binding (Fig. 2a).
Binding assays performed using four PrPC molecules presenting small deletions on the putative Vn binding site, revealed that the PrPC deletion mutants Δ105-112, Δ113-119, and Δ105-128 did not bind Vn, whereas mutants Δ51-90 and Δ120-125 exhibited binding capacity similar to that of the wild-type molecule (Fig. 2b). These data corroborate that the region comprising a.a. 105-119 of PrPC includes the binding site for Vn.
Protein: DP00265 (UniProt P04925)
Region: residues 95	to 110
Annotation: protein binding (Molecular function)
Evidence: immunohistochemistry evidence used in manual assertion
Supporting statements:
To distinguish whether the 95–110 charge cluster or the octapeptide repeat domain is crucial for Aβ42 binding, a mutant lacking the 52–91 segment was expressed. The Δ52–91 mutant exhibits significant Aβ42 binding, implicating the 95–110 region as a principal site for Aβ42-oligomer binding. Consistent with this hypothesis, deletion of 11 aa in the Δ95–105 variant reduces binding by 80%, and there was no further reduction in the Δ70–105 variant.
Protein: DP00265 (UniProt P04925)
Region: residues 95	to 110
Annotation: protein binding (Molecular function)
Evidence: blocking monoclonal antibody evidence used in manual assertion
Supporting statements:
Of six antibodies initially tested, only one (6D11) blocked the binding of Aβ42 assemblies to PrPC with an IC50 of 1 nM (Fig. 3b–d, Suppl. Fig. 8–10). The epitope for 6D11 corresponds to aa 93–109 of mouse PrPC, matching the conclusion that the 95–105 region is a primary determinant for binding. To confirm this hypothesis, we examined the effect of an additional antibody (8G8) with an overlapping epitope, aa 95–110. The 8G8 antibody blocked Aβ42-PrPC interaction, though with a lesser potency than 6D11.
Protein: DP00265 (UniProt P04925)
Region: residues 91	to 123
Annotation: metal ion binding (Molecular function)
Evidence: nuclear magnetic resonance evidence used in manual assertion
Supporting statements:
Location and properties of metal-binding sites on the human prion protein
In this protein, residues 91–123 are unstructured and the NMR analysis shows that during titration to stoichiometry the major shifts occur in this region, chiefly centered around histidine residues 96 and 111.

Hence, the single binding site for transition metals on PrP (91) is selective and follows the order Cu(II) >> Ni(II) > Zn(II) >> Mn(II).
Protein: DP00265 (UniProt P04925)
Region: residues 52	to 98
Annotation: metal ion binding (Molecular function)
Evidence: fluorescence evidence used in manual assertion
Supporting statements:
Location and properties of metal-binding sites on the human prion protein
Fig. ​Fig.33 shows a copper(II) titration of the octapeptide-repeat segment corresponding to residues 52–98.
Copper(II) binding in the absence of glycine is biphasic; there is an initial phase representing the occupation of a single tight site, giving the ≈40% quench, followed by a weak binding phase with a Kd of 15 μM, which accounts for the remaining 50% loss of indole fluorescence.
Nickel(II) binds with a dissociation constant of 2 × 10−8 M, some six orders of magnitude weaker than copper(II).
Protein: DP00265 (UniProt P04925)
Region: residues 93	to 109
Annotation: protein binding (Molecular function)
Evidence: blocking monoclonal antibody evidence used in manual assertion
Supporting statements:
a-synuclein interacts with PrPC to induce cognitive
impairment through mGluR5 and NMDAR2B
To investigate the region(s) of PrPC that mediate the aSyn effects, we targeted three regions in the protein using different antibodies against PrPC: 6D11 (epitope targeting the region 93–109 of PrPC; 100 nM), 8B4 (epitope targeting the N terminus of PrPC; 10 µg) and C-20 (epitope targeting the C terminus of PrPC; 10 µg) (Fig. 1d). In slices pre-treated with 6D11 antibody, the effect of aSyn oligomers on LTP was blocked (P < 0.001; Fig. 1c). In contrast, pre-treatment with 8B4 or C-20 had no effect (P > 0.05; Fig. 1c and Supplementary Fig. 1h). This suggests that the 93–109 segment of PrPC is the crucial region for aSyn-induced toxic effects.
Thus, PrPC deletion or blockade at the 93–109 segment prevents aSyn-oligomer-induced impairments in both LTP and basal synaptic transmission, suggesting that PrPC mediates this synaptic dysfunction in a 6D11-sensitive manner.
Protein: DP00265 (UniProt P04925)
Region: residues 93	to 109
Annotation: molecular function activator activity (Molecular function)
Evidence: quantitative western immunoblotting evidence used in manual assertion
Supporting statements:
We asked whether PrPC was required for the observed aSyn-induced Src activation, but we could not detect any effect of aSyn on Src activation in neuronal cultures from Prnp−/− mice (P > 0.05; Fig. 2e). In addition, we found that the 6D11 antibody prevented Src activation by aSyn (P < 0.001; Fig. 2d,e), whereas neither the 8B4 nor C-20 antibodies prevented Src phosphorylation.
Y1472 of NMDAR2B is a major phosphorylation site of Fyn kinase15. We examined total and phosphorylated levels  of Y1472 NMDAR2B in neuronal cultures exposed to aSyn oligomers for different time periods. After 5 min of exposure, an increase in the levels of phospho-NMDAR2B was already detected, with no changes in the total levels of NMDAR2B (Supplementary Fig. 3f,g). This increase was blocked by the 6D11 antibody and the Fyn inhibitor (PP1, 30 μM, 25 min; P < 0.05; Fig. 2f), but was not affected by the 8B4 or C-20 antibodies. Consistent with this, aSyn oligomers failed to induce further NMDAR2B phosphorylation in neuronal cultures from Prnp−/− mice (Fig. 2f).
Thus, aSyn requires PrPC, particularly the 93–109 region, to induce Fyn activation and subsequent NMDAR2B phosphorylation, which may underlie the LTP impairments observed in the presence of aSyn oligomers.
As a consequence of the aSyn-Prp mediated activation of Fun and hyperphosforilation of NMDAR2B, disregulation of Ca2+ occurs and subsequent synaptic disfunction. 

our data suggest that the amino acid region 93–109 of PrPC is involved in mediating the toxic effects of aSyn.
Protein: DP00265 (UniProt P04925)
Region: residues 93	to 109
Annotation: molecular adaptor activity (Molecular function)
Evidence: protein binding evidence used in manual assertion
Supporting statements:
Next, by pulling down PrPC, we detected Fyn, NMDAR2B and aSyn in the same complex in WT, but not in Prnp−/−, slices in both control and aSyn-exposed slices (Fig. 2h). This was further validated by reverse co-IP, in which we pulled down aSyn and detected NMDAR2B, Fyn and PrPC (Fig. 2h).
Importantly, PrPC is extracellular and both Fyn and NMDAR2B are intracellular proteins. Authors also report that mGluR5 transmembrane protein might act as molecular bridge between PrPC, Fyn and NMDAR2B. Although authors do not provide evidence of a direct interaction.
Protein: DP00265 (UniProt P04925)
Region: residues 93	to 109
Annotation: protein binding (Molecular function)
Evidence: qualitative western immunoblotting evidence used in manual assertion
Supporting statements:
When we immunoprecipitated either PrPC or aSyn from the hippocampus of aSyn transgenic mice, we detected the counterpart of the aSyn-PrPC complex (Fig. 2h)
Protein: DP00265 (UniProt P04925)
Region: residues 23	to 51
Annotation: protein binding (Molecular function)
Evidence: blocking monoclonal antibody evidence used in manual assertion
Supporting statements:
Two antibodies to two different epitopes of PrPC abrogated the inhibition of LTP by two different sources of tau, recombinant soluble aggregated tau and AD brain-soluble extract. On the basis of the present findings, PrPC appears to be a crucial site of action for tau-mediated disruption of synaptic plasticity in vivo. 
Both antibodies target specific regions of the disordered N.terminus of Prp. One of them, MI-0131 antibody targets specifically 23-51 region of Prp.
Protein: DP00265 (UniProt P04925)
Region: residues 93	to 109
Annotation: protein binding (Molecular function)
Evidence: blocking monoclonal antibody evidence used in manual assertion
Supporting statements:
Two antibodies to two different epitopes of PrPC abrogated the inhibition of LTP by two different sources of tau, recombinant soluble aggregated tau and AD brain-soluble extract. On the basis of the present findings, PrPC appears to be a crucial site of action for tau-mediated disruption of synaptic plasticity in vivo. 
Both antibodies target specific regions of the disordered N.terminus of Prp. 6D11 antibody targets 93-109 region of PRP.