LiteFold/DisProt huggingface dataset:
Protein: DP02598 (UniProt Q96H20)
Region: residues 1	to 25
Annotation: localization (Biological process)
Evidence: microscopy evidence used in manual assertion
Supporting statements:
Authors of the publication refer to the N-terminal 25 residues of VPS22 as VPS22-H0
We have now found that the most N-terminal predicted helix of the core of each subunit (H0) is flexibly attached to the core assembly. We have been able to assign functions to each of these two regions. The VPS22-H0 participates in membrane binding, while the VPS36-H0 interacts with ESCRT-I.
Cross-references: PDB:2ZME
PDB:3CUQ
Protein: DP02599 (UniProt Q86VN1)
Region: residues 149	to 169
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The linker between the GLUE domain and the C-terminal core of VPS36 (residues 140–169) also contains a predicted α helix, which we refer to as VPS36-H0
The VPS22-H0, VPS36-H0, and adjoining residues were disordered.
Residues 149–169 from VPS36 and residues 1–25 from VPS22 are present in construct a, but could not be visualized in electron density and are presumed to be disordered.
Cross-references: PDB:2ZME
Protein: DP02599 (UniProt Q86VN1)
Region: residues 149	to 169
Annotation: flexible linker (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The linker between the GLUE domain and the C-terminal core of VPS36 (residues 140–169) also contains a predicted α helix, which we refer to as VPS36-H0
The VPS22-H0, VPS36-H0, and adjoining residues were disordered.
Residues 149–169 from VPS36 and residues 1–25 from VPS22 are present in construct a, but could not be visualized in electron density and are presumed to be disordered.
Cross-references: PDB:2ZME
Protein: DP02600 (UniProt P35916)
Region: residues 470	to 483
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The structure of the VEGFR-3 D4-5 homodimer suggests that proteolytic cleavage did not introduce significant changes in the D5 conformation, because it occurred in the C-D loop, which is disordered in the Cys466/Cys486 disulfide bridge
Residues 470–483 in the C-D loop were disordered and thus were omitted from the final model. VEGFR-3 D4-5 has an overall extended structure connected by the linker peptide, a salt bridge between Glu344 and Lys539, and a hydrogen bond between Glu391 and Tyr448
Cross-references: PDB:4BSJ
Protein: DP02600 (UniProt P35916)
Region: residues 470	to 483
Annotation: flexible linker (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The structure of the VEGFR-3 D4-5 homodimer suggests that proteolytic cleavage did not introduce significant changes in the D5 conformation, because it occurred in the C-D loop, which is disordered in the Cys466/Cys486 disulfide bridge
Residues 470–483 in the C-D loop were disordered and thus were omitted from the final model. VEGFR-3 D4-5 has an overall extended structure connected by the linker peptide, a salt bridge between Glu344 and Lys539, and a hydrogen bond between Glu391 and Tyr448
Cross-references: PDB:4BSJ
Protein: DP02600 (UniProt P35916)
Region: residues 77	to 89
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
On the other hand, VEGFR-3 D1 has large disordered regions in the ligand complex, suggesting that it may interact with other binding partners in vivo, such as neuropilin-2 or the large N- and C-terminal propeptides of VEGF-C and VEGF-D.
Residues 28–134 of D1 are largely disordered, and we could build only the core of the apparent I-type Ig domain using KIT D1 (PDB ID code 2E9W) as a model.
Cross-references: PDB:4BSK
Protein: DP02600 (UniProt P35916)
Region: residues 114	to 123
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
On the other hand, VEGFR-3 D1 has large disordered regions in the ligand complex, suggesting that it may interact with other binding partners in vivo, such as neuropilin-2 or the large N- and C-terminal propeptides of VEGF-C and VEGF-D.
Residues 28–134 of D1 are largely disordered, and we could build only the core of the apparent I-type Ig domain using KIT D1 (PDB ID code 2E9W) as a model.
Cross-references: PDB:4BSK
Protein: DP02601 (UniProt Q96NW4)
Region: residues 693	to 732
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The first ankyrin repeat (coloured cyan in all figures), although separated from the next five repeats by a disordered region (residues 694–729) for which there is no electron density, contacts the second ankyrin repeat through an extensive and tightly packed hydrophobic interface (Figure 3).
Cross-references: PDB:4B93
Protein: DP02601 (UniProt Q96NW4)
Region: residues 693	to 732
Annotation: flexible linker (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The first ankyrin repeat (coloured cyan in all figures), although separated from the next five repeats by a disordered region (residues 694–729) for which there is no electron density, contacts the second ankyrin repeat through an extensive and tightly packed hydrophobic interface (Figure 3).
Cross-references: PDB:4B93
Protein: DP02601 (UniProt Q96NW4)
Region: residues 619	to 640
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
 The final model comprises three molecules of the complex in the asymmetric unit, where VARP (residues 452–618), Rab32 (residues 22–198), and Rab32’s bound GppCp:Mg2+ are well defined in the electron density map (Figures S1C and S1D).
Cross-references: PDB:4CYM
Protein: DP02602 (UniProt P70280)
Region: residues 164	to 188
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
In the Varp–VAMP7 complex, the final 24 residues of the VAMP7 cytosolic region (164–188), which are dispensable for binding to Varp (Fig. 1 and Supplementary Fig. 6), are not visible in the structure.
Cross-references: PDB:4B93
Protein: DP02604 (UniProt P20020-1)
Region: residues 1063	to 1258
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The C-terminal autoinhibitory domain and the phospholipid-binding domain in the first cytosolic loop of the PMCAs are not resolved, suggesting structural flexibility in these regions.
PMCAs have a unique autoinhibitory domain at N terminus (in plants) or C terminus (in mammals)
Cross-references: PDB:6A69
Protein: DP02604 (UniProt P20020-1)
Region: residues 1063	to 1258
Annotation: molecular function inhibitor activity (Molecular function)
Evidence: cryogenic electron microscopy evidence used in manual assertion
Supporting statements:
The C-terminal autoinhibitory domain and the phospholipid-binding domain in the first cytosolic loop of the PMCAs are not resolved, suggesting structural flexibility in these regions.
PMCAs have a unique autoinhibitory domain at N terminus (in plants) or C terminus (in mammals)
Cross-references: PDB:6A69
Protein: DP02605 (UniProt P02533)
Region: residues 295	to 331
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
We crystallized a complex of K5 L2-2B and K14 L2-2B (Fig. 1a), which behaves as a functional assembly intermediate in vitro and in vivo (Supplementary Fig. 1a–c). The resulting structure includes residues Thr382– Gly476 of K5 and Ser332–Gly421 of K14 (Supplementary Fig. 1d). The L2 region and N-terminal end of the 2B domains of K5 and K14 are not well ordered in the crystal, and we did not model them.
Cross-references: PDB:3TNU
Protein: DP02605 (UniProt P02533)
Region: residues 295	to 331
Annotation: flexible linker (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
We crystallized a complex of K5 L2-2B and K14 L2-2B (Fig. 1a), which behaves as a functional assembly intermediate in vitro and in vivo (Supplementary Fig. 1a–c). The resulting structure includes residues Thr382– Gly476 of K5 and Ser332–Gly421 of K14 (Supplementary Fig. 1d). The L2 region and N-terminal end of the 2B domains of K5 and K14 are not well ordered in the crystal, and we did not model them.
Although variable in size (40–240 kDa) and primary structure, all intermediate filament proteins feature a central α-helical rod domain of conserved length and substructure comprising four heptad repeat– containing segments (1A, 1B, 2A and 2B) interrupted by three short linker sequences (L1, L12 and L2) at conserved locations
Cross-references: PDB:3TNU
Protein: DP02606 (UniProt P13647)
Region: residues 350	to 381
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
We crystallized a complex of K5 L2-2B and K14 L2-2B (Fig. 1a), which behaves as a functional assembly intermediate in vitro and in vivo (Supplementary Fig. 1a–c). The resulting structure includes residues Thr382– Gly476 of K5 and Ser332–Gly421 of K14 (Supplementary Fig. 1d). The L2 region and N-terminal end of the 2B domains of K5 and K14 are not well ordered in the crystal, and we did not model them. X-ray data collection and refinement statistics are reported in Table 1. The structure of the 2B domain of K5–K14 reveals a typical left-handed coiled-coil dimer, with the two α-helices oriented in parallel and in register (Fig. 1b) and one coiled-coil heterodimer of K5–K14 2B domains per asymmetric unit.
Cross-references: PDB:3TNU
Protein: DP02606 (UniProt P13647)
Region: residues 350	to 381
Annotation: flexible linker (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
We crystallized a complex of K5 L2-2B and K14 L2-2B (Fig. 1a), which behaves as a functional assembly intermediate in vitro and in vivo (Supplementary Fig. 1a–c). The resulting structure includes residues Thr382– Gly476 of K5 and Ser332–Gly421 of K14 (Supplementary Fig. 1d). The L2 region and N-terminal end of the 2B domains of K5 and K14 are not well ordered in the crystal, and we did not model them. X-ray data collection and refinement statistics are reported in Table 1. The structure of the 2B domain of K5–K14 reveals a typical left-handed coiled-coil dimer, with the two α-helices oriented in parallel and in register (Fig. 1b) and one coiled-coil heterodimer of K5–K14 2B domains per asymmetric unit.
Although variable in size (40–240 kDa) and primary structure, all intermediate filament proteins feature a central α-helical rod domain of conserved length and substructure comprising four heptad repeat– containing segments (1A, 1B, 2A and 2B) interrupted by three short linker sequences (L1, L12 and L2) at conserved locations
Cross-references: PDB:3TNU
Protein: DP02606 (UniProt P13647)
Region: residues 1	to 167
Annotation: disorder (Structural state)
Evidence: author statement used in manual assertion
Supporting statements:
All IF proteins share a common tripartite structure consisting of a central α-helical rod domain, and disordered N-terminal head and C-terminal tail domains.
The rod domain corresponds to the 168-481 region.
Protein: DP02606 (UniProt P13647)
Region: residues 482	to 590
Annotation: disorder (Structural state)
Evidence: author statement used in manual assertion
Supporting statements:
All IF proteins share a common tripartite structure consisting of a central α-helical rod domain, and disordered N-terminal head and C-terminal tail domains.
The rod domain corresponds to the 168-481 region.
Protein: DP02606 (UniProt P13647)
Region: residues 1	to 167
Annotation: disorder (Structural state)
Evidence: author statement used in manual assertion
Supporting statements:
Current understanding on the head and tail domains indicates that these correspond with intrinsically-disordered regions of the keratin protein [21].
The head domain corresponds to the 1-167 region.
Protein: DP02606 (UniProt P13647)
Region: residues 478	to 590
Annotation: disorder (Structural state)
Evidence: author statement used in manual assertion
Supporting statements:
Current understanding on the head and tail domains indicates that these correspond with intrinsically-disordered regions of the keratin protein [21].
The tail domain corresponds to the 478-590 region.
Protein: DP02607 (UniProt Q9UNA0)
Region: residues 557	to 628
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Although the amino acid sequence of the crystallized protein encompasses three domains—catalytic, disintegrin-like domain, and thrombospondin-like domain—the latter domain, residues 557–628, has no supporting electron density, presumably because of disorder.
Cross-references: PDB:2RJQ
Protein: DP02607 (UniProt Q9UNA0)
Region: residues 557	to 628
Annotation: molecular function regulator (Molecular function)
Evidence: combinatorial experimental and author inference evidence contained in single publication used in manual assertion
Supporting statements:
Although the amino acid sequence of the crystallized protein encompasses three domains—catalytic, disintegrin-like domain, and thrombospondin-like domain—the latter domain, residues 557–628, has no supporting electron density, presumably because of disorder.
In combination with the thrombospondin type I domain, the disintegrin-like domain was proposed to play an important role in recognition of substrate folding topology (Lauer-Fields et al. 2007).
Cross-references: PDB:2RJQ
Protein: DP02608 (UniProt Q8IUQ4)
Region: residues 90	to 124
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
No electron density was observed for residues 90-124.
Cross-references: PDB:2A25
Protein: DP02609 (UniProt Q96PY5)
Region: residues 150	to 204
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The flexible loop of 55 residues that is not resolved in the electron density map of the FMNL2N–Cdc42 structure is directly preceding the second basic helix α9. Interestingly, this loop is missing in one splice variant of FMNL3, isoform 2, but otherwise conserved in all FMNLs
Cross-references: PDB:4YC7
Protein: DP02609 (UniProt Q96PY5)
Region: residues 150	to 204
Annotation: flexible linker (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The flexible loop of 55 residues that is not resolved in the electron density map of the FMNL2N–Cdc42 structure is directly preceding the second basic helix α9. Interestingly, this loop is missing in one splice variant of FMNL3, isoform 2, but otherwise conserved in all FMNLs
Proteomic analyses identified a phosphorylation site for S171 (ref. 41), which is in the centre of the flexible loop preceding helix α9 (Supplementary Fig. 4) and not resolved in the crystal structure.
Cross-references: PDB:4YC7
Protein: DP02609 (UniProt Q96PY5)
Region: residues 169	to 173
Annotation: phosphorylation display site (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The flexible loop of 55 residues that is not resolved in the electron density map of the FMNL2N–Cdc42 structure is directly preceding the second basic helix α9. Interestingly, this loop is missing in one splice variant of FMNL3, isoform 2, but otherwise conserved in all FMNLs
Proteomic analyses identified a phosphorylation site for S171 (ref. 41), which is in the centre of the flexible loop preceding helix α9 (Supplementary Fig. 4) and not resolved in the crystal structure.
Cross-references: PDB:4YC7
Protein: DP02610 (UniProt P22449)
Region: residues 368	to 382
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Electron density is apparent for all residues except those at the amino (133–140) and carboxyl (368–382) termini of the domain and within the loop between α helices 1 and 3 (the 1/3 loop, residues 157–165).
Cross-references: PDB:1M7W
Protein: DP02611 (UniProt Q8N1G2)
Region: residues 126	to 140
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The figure-of-merit after phasing (before solvent modification) was 0.4, and the resulting experimental electron density maps were well defined, allowing the tracing of a model that consisted of residues 141–544 of the protein.
Cross-references: PDB:4N4A
PDB:4N48
PDB:4N49
Protein: DP02612 (UniProt Q9Y6D6)
Region: residues 50	to 63
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
We then determined the crystal structure of Arl1-GTP–DCB at 3.4 Å resolution (Supplementary Table S1). In the structure, each asymmetric unit contains one Arl1 (residues 17–181) bound with a GTP and a Mg2+ ion at the active site and one DCB domain (residues 14–49 and 64–221) (Figure 1B).
Cross-references: PDB:5J5C
Protein: DP02612 (UniProt Q9Y6D6)
Region: residues 50	to 63
Annotation: flexible linker (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
We then determined the crystal structure of Arl1-GTP–DCB at 3.4 Å resolution (Supplementary Table S1). In the structure, each asymmetric unit contains one Arl1 (residues 17–181) bound with a GTP and a Mg2+ ion at the active site and one DCB domain (residues 14–49 and 64–221)
The DCB domain consists of eight α-helices forming four HEAT (Huntingtin, Elongation factor 3, protein phosphatase 2A, and the yeast kinase TOR1) repeats, and each repeat comprises of a pair of antiparallel α-helices connected by a flexible linker, resembling that in Thielavia terrestris Sec7 protein (Richardson et al., 2016) (Supplementary Figure S4A).
Cross-references: PDB:5J5C
Protein: DP02612 (UniProt Q9Y6D6)
Region: residues 1	to 13
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
We then determined the crystal structure of Arl1-GTP–DCB at 3.4 Å resolution (Supplementary Table S1). In the structure, each asymmetric unit contains one Arl1 (residues 17–181) bound with a GTP and a Mg2+ ion at the active site and one DCB domain (residues 14–49 and 64–221) (Figure 1B).
Cross-references: PDB:5J5C
Protein: DP02613 (UniProt Q8K368)
Region: residues 554	to 563
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
In free FANCI, it forms the β3-β4 sheet and part of it is disordered.
Cross-references: PDB:3S51
PDB:3S4Z
Protein: DP02613 (UniProt Q8K368)
Region: residues 554	to 563
Annotation: disorder to order (Structural transition)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
This region undergoes a complete conformational change on FANCD2 binding. In free FANCI, it forms the β3-β4 sheet and part of it is disordered.
Cross-references: PDB:3S4W
Protein: DP02613 (UniProt Q8K368)
Region: residues 554	to 563
Annotation: phosphorylation display site (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
These three sites map to the 37-amino acid FANCI-specific HD2 insertion at the I-D interface. This region undergoes a complete conformational change on FANCD2 binding. In free FANCI, it forms the β3-β4 sheet and part of it is disordered.
The five FANCI phosphorylation sites cluster at HD2, at and near the I-D interface. Only three of these sites have the ATM/ATR kinase consensus and are also conserved in vertebrates (Ser555, Thr558, Thr564 in mouse FANCI).
In the ID complex it instead forms two new helices (α26b and α26c) and a 10-residue extension to α27, becoming ordered in its entirety (Fig. 3C). This changes entirely the structural context of the phosphorylation sites. In free FANCI, they map to the disordered segment where they can be readily phosphorylated. In the complex, they end up at the start, middle and immediately after the α26c helix. Their side chains are embedded in hydrogen bond networks that anchor α26c in the FANCI structure and also contact FANCD2 (Fig. 3D and Fig. 2B bottom panel). The structure suggests that their phosphorylation may augment the intramolecular hydrogen bond networks, stabilizing the FANCD2-bound conformation of this region, and may also result in new FANCD2 contacts
Phosphorylation sites map to a disordered region that undergoes a disorder to order transition upon binding of FANCD2
Cross-references: PDB:3S4W
Protein: DP02613 (UniProt Q8K368)
Region: residues 554	to 563
Annotation: protein binding (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
These three sites map to the 37-amino acid FANCI-specific HD2 insertion at the I-D interface. This region undergoes a complete conformational change on FANCD2 binding. In free FANCI, it forms the β3-β4 sheet and part of it is disordered.
In the ID complex it instead forms two new helices (α26b and α26c) and a 10-residue extension to α27, becoming ordered in its entirety (Fig. 3C). This changes entirely the structural context of the phosphorylation sites. In free FANCI, they map to the disordered segment where they can be readily phosphorylated. In the complex, they end up at the start, middle and immediately after the α26c helix. Their side chains are embedded in hydrogen bond networks that anchor α26c in the FANCI structure and also contact FANCD2 (Fig. 3D and Fig. 2B bottom panel). The structure suggests that their phosphorylation may augment the intramolecular hydrogen bond networks, stabilizing the FANCD2-bound conformation of this region, and may also result in new FANCD2 contacts
Cross-references: PDB:3S4W
Protein: DP02613 (UniProt Q8K368)
Region: residues 554	to 563
Annotation: molecular function regulator (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
Our data implicate the ID complex in recognizing DNA structures that result from the encounter of replication forks with an ICL. The complex may function in stabilizing and protecting these DNA structures, and also in providing specificity for the initial incisions around the ICL by directing the FA-associated nuclease to these sites.