LiteFold/DisProt huggingface dataset:
Protein: DP02772 (UniProt P0DTC2)
Region: residues 681	to 686
Annotation: positive regulation of viral entry into host cell (Biological process)
Evidence: immunodetection assay evidence used in manual assertion
Supporting statements:
Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases.
Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming.
The present study provides evidence that host cell entry of SARS-CoV-2 depends on the SARS-CoV receptor ACE2 and can be blocked by a clinically proven inhibitor of the cellular serine protease TMPRSS2, which is employed by SARS-CoV-2 for S protein priming.
These results suggest efficient proteolytic processing of SARS-2-S in human cells, in keeping with the presence of several arginine residues at the S1/S2 cleavage site of SARS-2-S but not SARS-S.
Protein: DP02772 (UniProt P0DTC2)
Region: residues 437	to 508
Annotation: positive regulation of viral entry into host cell (Biological process)
Evidence: immunodetection assay evidence used in manual assertion
Supporting statements:
Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases.
Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming.
Moreover, antiserum raised against human ACE2 blocked SARS-S- and SARS-2-S- but not VSV-G- or MERS-S-driven entry (Figure 3B). Finally, authentic SARS-CoV-2 infected BHK-21 cells transfected to express ACE2 cells but not parental BHK-21 cells with high efficiency (Figure 3C), indicating that SARS-2-S, like SARS-S, uses ACE2 for cellular entry.
Protein: DP02772 (UniProt P0DTC2)
Region: residues 681	to 686
Annotation: limited proteolysis display site (Disorder function)
Evidence: immunodetection assay evidence used in manual assertion
Supporting statements:
Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases.
Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming.
The present study provides evidence that host cell entry of SARS-CoV-2 depends on the SARS-CoV receptor ACE2 and can be blocked by a clinically proven inhibitor of the cellular serine protease TMPRSS2, which is employed by SARS-CoV-2 for S protein priming.
These results suggest efficient proteolytic processing of SARS-2-S in human cells, in keeping with the presence of several arginine residues at the S1/S2 cleavage site of SARS-2-S but not SARS-S.
Protein: DP02772 (UniProt P0DTC2)
Region: residues 16	to 21
Annotation: glycosylation display site (Disorder function)
Evidence: mass spectrometry evidence used in manual assertion
Supporting statements:
To determine the site-specific glycosylation of SARS-CoV-2 S, we employed trypsin, chymotrypsin, and alphalytic protease to generate three glycopeptide samples. These proteases were selected to generate glycopeptides that contain a single N-linked glycan sequon. The glycopeptides were analyzed by liquid-chromatography-mass spectrometry (LC-MS), and the glycan compositions were determined for all 22 N-linked glycan sites (Fig. 2). Although unoccupied glycosylation sites were detected on SARS-CoV-2 S, when quantified they were revealed to form a very minor component of the total peptide pool (table S2).
Protein: DP02772 (UniProt P0DTC2)
Region: residues 330	to 335
Annotation: glycosylation display site (Disorder function)
Evidence: mass spectrometry evidence used in manual assertion
Supporting statements:
To determine the site-specific glycosylation of SARS-CoV-2 S, we employed trypsin, chymotrypsin, and alphalytic protease to generate three glycopeptide samples. These proteases were selected to generate glycopeptides that contain a single N-linked glycan sequon. The glycopeptides were analyzed by liquid-chromatography-mass spectrometry (LC-MS), and the glycan compositions were determined for all 22 N-linked glycan sites (Fig. 2). Although unoccupied glycosylation sites were detected on SARS-CoV-2 S, when quantified they were revealed to form a very minor component of the total peptide pool (table S2).
Protein: DP02772 (UniProt P0DTC2)
Region: residues 73	to 78
Annotation: glycosylation display site (Disorder function)
Evidence: mass spectrometry evidence used in manual assertion
Supporting statements:
To determine the site-specific glycosylation of SARS-CoV-2 S, we employed trypsin, chymotrypsin, and alphalytic protease to generate three glycopeptide samples. These proteases were selected to generate glycopeptides that contain a single N-linked glycan sequon. The glycopeptides were analyzed by liquid-chromatography-mass spectrometry (LC-MS), and the glycan compositions were determined for all 22 N-linked glycan sites (Fig. 2). Although unoccupied glycosylation sites were detected on SARS-CoV-2 S, when quantified they were revealed to form a very minor component of the total peptide pool (table S2).
We characterized the N-linked glycans on extended flexible loop structures (N74 and N149) and at the membrane-proximal C terminus (N1158, N1173, N1194) that were not resolved in the cryo-EM maps (4) These were determined to be complex-type glycans, consistent with steric accessibility of these residues.
Legend Fig 3. Note that the flexible loops on which N74 and N149 glycan sites reside are represented as dashed lines with glycan sites on the loops mapped at their approximate regions.
Protein: DP02772 (UniProt P0DTC2)
Region: residues 148	to 153
Annotation: glycosylation display site (Disorder function)
Evidence: mass spectrometry evidence used in manual assertion
Supporting statements:
To determine the site-specific glycosylation of SARS-CoV-2 S, we employed trypsin, chymotrypsin, and alphalytic protease to generate three glycopeptide samples. These proteases were selected to generate glycopeptides that contain a single N-linked glycan sequon. The glycopeptides were analyzed by liquid-chromatography-mass spectrometry (LC-MS), and the glycan compositions were determined for all 22 N-linked glycan sites (Fig. 2). Although unoccupied glycosylation sites were detected on SARS-CoV-2 S, when quantified they were revealed to form a very minor component of the total peptide pool (table S2).
We characterized the N-linked glycans on extended flexible loop structures (N74 and N149) and at the membrane-proximal C terminus (N1158, N1173, N1194) that were not resolved in the cryo-EM maps (4) These were determined to be complex-type glycans, consistent with steric accessibility of these residues.
Legend Fig 3. Note that the flexible loops on which N74 and N149 glycan sites reside are represented as dashed lines with glycan sites on the loops mapped at their approximate regions.
Protein: DP02772 (UniProt P0DTC2)
Region: residues 1157	to 1162
Annotation: glycosylation display site (Disorder function)
Evidence: mass spectrometry evidence used in manual assertion
Supporting statements:
To determine the site-specific glycosylation of SARS-CoV-2 S, we employed trypsin, chymotrypsin, and alphalytic protease to generate three glycopeptide samples. These proteases were selected to generate glycopeptides that contain a single N-linked glycan sequon. The glycopeptides were analyzed by liquid-chromatography-mass spectrometry (LC-MS), and the glycan compositions were determined for all 22 N-linked glycan sites (Fig. 2). Although unoccupied glycosylation sites were detected on SARS-CoV-2 S, when quantified they were revealed to form a very minor component of the total peptide pool (table S2).
We characterized the N-linked glycans on extended flexible loop structures (N74 and N149) and at the membrane-proximal C terminus (N1158, N1173, N1194) that were not re-solved in the cryo-EM maps (4) These were determined to be complex-type glycans, consistent with steric accessibility of these residues.
Protein: DP02772 (UniProt P0DTC2)
Region: residues 1172	to 1177
Annotation: glycosylation display site (Disorder function)
Evidence: mass spectrometry evidence used in manual assertion
Supporting statements:
To determine the site-specific glycosylation of SARS-CoV-2 S, we employed trypsin, chymotrypsin, and alphalytic protease to generate three glycopeptide samples. These proteases were selected to generate glycopeptides that contain a single N-linked glycan sequon. The glycopeptides were analyzed by liquid-chromatography-mass spectrometry (LC-MS), and the glycan compositions were determined for all 22 N-linked glycan sites (Fig. 2). Although unoccupied glycosylation sites were detected on SARS-CoV-2 S, when quantified they were revealed to form a very minor component of the total peptide pool (table S2).
We characterized the N-linked glycans on extended flexible loop structures (N74 and N149) and at the membrane-proximal C terminus (N1158, N1173, N1194) that were not re-solved in the cryo-EM maps (4) These were determined to be complex-type glycans, consistent with steric accessibility of these residues.
Protein: DP02772 (UniProt P0DTC2)
Region: residues 1194	to 1198
Annotation: glycosylation display site (Disorder function)
Evidence: mass spectrometry evidence used in manual assertion
Supporting statements:
To determine the site-specific glycosylation of SARS-CoV-2 S, we employed trypsin, chymotrypsin, and alphalytic protease to generate three glycopeptide samples. These proteases were selected to generate glycopeptides that contain a single N-linked glycan sequon. The glycopeptides were analyzed by liquid-chromatography-mass spectrometry (LC-MS), and the glycan compositions were determined for all 22 N-linked glycan sites (Fig. 2). Although unoccupied glycosylation sites were detected on SARS-CoV-2 S, when quantified they were revealed to form a very minor component of the total peptide pool (table S2).
We characterized the N-linked glycans on extended flexible loop structures (N74 and N149) and at the membrane-proximal C terminus (N1158, N1173, N1194) that were not re-solved in the cryo-EM maps (4) These were determined to be complex-type glycans, consistent with steric accessibility of these residues.
Protein: DP02772 (UniProt P0DTC2)
Region: residues 319	to 541
Annotation: disorder to order (Structural transition)
Evidence: cryogenic electron microscopy evidence used in manual assertion
Supporting statements:
Here, we present cryo-electron microscopy structures of full-length human ACE2 in the presence of the neutral amino acid transporter B0AT1 with or without the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) of SARS-CoV-2, both at an overall resolution of 2.9 angstroms, with a local resolution of 3.5 angstroms at the ACE2-RBD interface.
The region corresponds to the so called RBM or Receptor Binding Motif, a region that is a flexible and disordered loop in the unbound state, and becomes ordered in all the available ACE2-bound SARS-CoV-2 Spike structures. Flexibility in the unbound state can be observed in PDB:6VSB [PMID: 32075877] and PDB:6VYB [PMID: 32155444] and the ordering that occurs in the ACE-2 bound form can be seen in PDB: 6M17 [PMID: 32132184] and PDB: 6MOJ [PMID: 32225176]
Cross-references: PDB:6M17
EMDB:30039
EMDB:30046
Protein: DP02781 (UniProt Q9UPY3)
Region: residues 1003	to 1029
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Surprisingly, the hDicer-specific-segment, that forms the ‘hDicer-specific helix’ in the structure of hDicer PAZ cassette-siRNA 12-mer complex (Figure 1D) is melted/disordered (spanning residues 1005-1019) in the hDicer PAZ cassette-siRNA 16-mer complex (Figure 6B, dotted red line).
Due to a shift in the numbering used by the authors, the missing residues correspond to UNIPROT numbering 1003-1029
The authors mention only the disordering of the specific helix (1015-1029), but in the structure the preceding loop (1003-1014) is also disordered, so in this structure both the loop and helix are disordered. This is the 16-mer siRNA bound enzyme and represents the cleavage competent state
We propose that our structure of the hDicer PAZ cassette-siRNA 16-mer complex (Figure 6B), where the Dicer-specific segment is disordered/melted, likely reflects the cleavage-competent conformation.
Cross-references: PDB:4NHA
Protein: DP02781 (UniProt Q9UPY3)
Region: residues 1003	to 1013
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
One of the unexpected features of the structure of the hDicer PAZ cassette-siRNA 12-mer complex is the identification of a disordered segment (993-1003), followed by an α-helical segment (1006-1020), with the latter designated the ‘hDicer-specific helix’. This helix extends out from the surface of the protein in a knob-like manner (Figure 1D, E), and in turn orients the bound siRNA duplex at an angle (approximately 60°) away from the surface of the protein
We postulate that the knob-like orientation of the hDicer-specific helix in hDicer PAZ cassette-siRNA 12-mer complex, wherein the bound siRNA is aligned at approximately 60° to the flat surface of the hDicer PAZ cassette, may represent the conformation associated with product release/transfer (Figure 7B)
The numbering used by authors is shifted by 10. The disordered segment (993-1003 by the authors) corresponds to residues 1003-1013 in the UNIPROT numbering. In this structure of hDICER with a 12-mer siRNA, the loop preceding the terminal helix (1003-1013) is disordered. This is the 12-mer siRNA bound enzyme and represents the product/release state
Cross-references: PDB:4NGD
Protein: DP02781 (UniProt Q9UPY3)
Region: residues 1013	to 1029
Annotation: disorder to order (Structural transition)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
One of the unexpected features of the structure of the hDicer PAZ cassette-siRNA 12-mer complex is the identification of a disordered segment (993-1003), followed by an α-helical segment (1006-1020), with the latter designated the ‘hDicer-specific helix’. This helix extends out from the surface of the protein in a knob-like manner (Figure 1D, E), and in turn orients the bound siRNA duplex at an angle (approximately 60°) away from the surface of the protein
Surprisingly, the hDicer-specific-segment, that forms the ‘hDicer-specific helix’ in the structure of hDicer PAZ cassette-siRNA 12-mer complex (Figure 1D) is melted/disordered (spanning residues 1005-1019) in the hDicer PAZ cassette-siRNA 16-mer complex (Figure 6B, dotted red line).
The numbering used by authors is shifted by 10. In the hDICER bound to the 12-mer siRNA, the disordered segment (993-1003 by the authors) corresponds to residues 1003-1013 in the UNIPROT numbering. In the hDICER structure bound to 16-mer siRNA, the disordered segment extends to include the terminal helix (residues 1003-1029) and therefore residues 1014-1029 corresponding to the terminal helix become ordered.
Cross-references: PDB:4NGD
PDB:4NHA
Protein: DP02782 (UniProt Q9NPI8)
Region: residues 211	to 234
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The capping helix α1 is linked to the first hairpin (HP1: helices α2 and α3) through an 11-residue loop that is disordered in the crystals. Hairpins HP1 and HP2 are connected by a highly charged, 23-residue loop L2 (residues 211-234) that is also disordered in the crystals.
The C-terminal domain, CTD, spans residues 156-357 of of FANCF
Cross-references: PDB:2IQC
Protein: DP02782 (UniProt Q9NPI8)
Region: residues 177	to 188
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The capping helix α1 is linked to the first hairpin (HP1: helices α2 and α3) through an 11-residue loop that is disordered in the crystals. Hairpins HP1 and HP2 are connected by a highly charged, 23-residue loop L2 (residues 211-234) that is also disordered in the crystals.
The C-terminal domain, CTD, spans residues 156-357 of of FANCF
Cross-references: PDB:2IQC
Protein: DP02783 (UniProt P49189)
Region: residues 232	to 255
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Moreover, the αβE region consisting of an α-helix and a β-strand of the coenzyme domain at the dimer interface are disordered, likely due to the loss of interactions with the inter-domain linker, which leads to incomplete β-nicotinamide adenine dinucleotide (NAD+) binding pocket.
Although the enzyme was co-crystallized with the β-nicotinamide adenine dinucleotide (NAD+) coenzyme, all structures, which are very similar, are devoid of NAD+ and display the same disordered region forming the coenzyme binding site.
The αβE region is not visible in the electron density maps thus is highly mobile (Figure 3C,D). The αE helix delineates the coenzyme cavity and possesses conserved residues known to bind the pyrophosphate moiety such as Ser233 and Thr236 (Ser242 and Thr245 in GmALDH9A2). 
This region interacts with the bound NAD+ when present in ALDH structures, and the absence of a bound NAD+ in the HsALDH9A1 structure is in agreement with this largely disordered region.
Cross-references: PDB:6QAO
PDB:6QAK
PDB:6QAP
Protein: DP02783 (UniProt P49189)
Region: residues 232	to 255
Annotation: small molecule binding (Molecular function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Moreover, the αβE region consisting of an α-helix and a β-strand of the coenzyme domain at the dimer interface are disordered, likely due to the loss of interactions with the inter-domain linker, which leads to incomplete β-nicotinamide adenine dinucleotide (NAD+) binding pocket.
Although the enzyme was co-crystallized with the β-nicotinamide adenine dinucleotide (NAD+) coenzyme, all structures, which are very similar, are devoid of NAD+ and display the same disordered region forming the coenzyme binding site.
The αβE region is not visible in the electron density maps thus is highly mobile (Figure 3C,D). The αE helix delineates the coenzyme cavity and possesses conserved residues known to bind the pyrophosphate moiety such as Ser233 and Thr236 (Ser242 and Thr245 in GmALDH9A2). 
This region interacts with the bound NAD+ when present in ALDH structures, and the absence of a bound NAD+ in the HsALDH9A1 structure is in agreement with this largely disordered region.
Cross-references: PDB:6QAO
PDB:6QAK
PDB:6QAP
Protein: DP02784 (UniProt P16892)
Region: residues 164	to 179
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The final models of npFus3, Fus3VF, Fus3/Ste7_pep1, Fus3/Msg5_pep, and Fus3/Far1_pep contain a full-length model of Fus3 (1–353) interspersed with a flexible segment encompassing part of the activation loop (164–179). This region appears to be flexible and invisible in all the structures.
Cross-references: PDB:2B9J
PDB:2B9F
PDB:2B9H
PDB:2B9I
Protein: DP02785 (UniProt P16278)
Region: residues 531	to 544
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Residues 531–544 were not visible in the electron density maps of the four β-Gal monomers in asymmetric units; therefore, these residues were not modeled.
The crystal structure showed that Arg-530 and Asn545 are separated by about 40 Å, and they point in opposite directions. Therefore, it seems that these residues were connected by a flexible loop before trypsinization. 
Cross-references: PDB:3THC
PDB:3THD
Protein: DP02785 (UniProt P16278)
Region: residues 531	to 544
Annotation: flexible linker (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Residues 531–544 were not visible in the electron density maps of the four β-Gal monomers in asymmetric units; therefore, these residues were not modeled.
The crystal structure showed that Arg-530 and Asn545 are separated by about 40 Å, and they point in opposite directions. Therefore, it seems that these residues were connected by a flexible loop before trypsinization. 
Flexible linker connecting β-domain 1 (residues 397–514) and β-domain 2 (residues 545–647)
Cross-references: PDB:3THC
PDB:3THD
Protein: DP02785 (UniProt P16278)
Region: residues 648	to 677
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Residues after Ser-647 were not visible in the electron density map.
Cross-references: PDB:3THC
PDB:3THD
Protein: DP02786 (UniProt Q9Y823)
Region: residues 406	to 418
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Subdomain II (residues 351–405) consists of a three-helix bundle composed of α11-α13. The residues after the α13 helix are disordered in SpHCS structures and are not reported here.
Cross-references: PDB:3IVT
PDB:3IVS
PDB:3IVU
Protein: DP02786 (UniProt Q9Y823)
Region: residues 129	to 141
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Although the overall alterations between the catalytic domains of the apoenzyme and 2-OG complex are relatively modest (root mean square deviation value of 1.25 Å for all aligned atoms), pronounced structural changes occur in the linker between β4 and α4 that is disordered in the apoenzyme. Binding of 2-OG induces ordering of the linker, resulting in the formation of the 3104 helix and the β4.1-β4.2 hairpin. RES
Cross-references: PDB:3IVS
Protein: DP02786 (UniProt Q9Y823)
Region: residues 129	to 141
Annotation: disorder to order (Structural transition)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Although the overall alterations between the catalytic domains of the apoenzyme and 2-OG complex are relatively modest (root mean square deviation value of 1.25 Å for all aligned atoms), pronounced structural changes occur in the linker between β4 and α4 that is disordered in the apoenzyme. Binding of 2-OG induces ordering of the linker, resulting in the formation of the 3104 helix and the β4.1-β4.2 hairpin. RES
Cross-references: PDB:3IVS
PDB:3IVT
PDB:3IVU
Protein: DP02786 (UniProt Q9Y823)
Region: residues 320	to 333
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
In the structures of the HCS apoenzyme and one of the 2-OG binary complexes, a lid motif from the C-terminal domain occludes the entrance to the active site of the neighboring monomer, whereas in the second 2-OG complex the lid is disordered, suggesting that it regulates substrate access to the active site through its apparent flexibility.
In the course of screening crystals of the SpHCS·2-OG complex, we identified two different conformations of the lid motif (residues 320–333) that encloses the entrance to the active site, which we term the closed and open conformations. In the closed lid complex (2.67 Å resolution), the lid motif is clearly visible in the electron density map and obstructs the entrance to the active site, whereas in the open complex (2.72 Å resolution), density for the lid is absent, resulting in a solvent-exposed active site.
Cross-references: PDB:3IVU