LiteFold/DisProt huggingface dataset:
Protein: DP03296 (UniProt P60484)
Region: residues 366	to 385
Annotation: protein binding (Molecular function)
Evidence: protein hydrogen-deuterium exchange mass spectrometry evidence used in manual assertion
Supporting statements:
HDX–MS shows that the phosphorylated C-terminal tail forms intramolecular interactions with both the C2 and the phosphatase domains
Overall, these decreases in HDX suggest that the fully phosphorylated C-terminal tail makes contact at the C2/phosphatase interface and more extensive contacts within the phosphatase domain, interacting extensively with all three loops of the active site and the PBM.
Region inside the disordered C-terminal tail that include multiple phosphorylation sites: T366, S370, S380, T382, T383, S385
Protein: DP03296 (UniProt P60484)
Region: residues 366	to 385
Annotation: self-assembly (Disorder function)
Evidence: protein hydrogen-deuterium exchange mass spectrometry evidence used in manual assertion
Supporting statements:
HDX–MS shows that the phosphorylated C-terminal tail forms intramolecular interactions with both the C2 and the phosphatase domains
Overall, these decreases in HDX suggest that the fully phosphorylated C-terminal tail makes contact at the C2/phosphatase interface and more extensive contacts within the phosphatase domain, interacting extensively with all three loops of the active site and the PBM.
Region inside the disordered C-terminal tail that include multiple phosphorylation sites: T366, S370, S380, T382, T383, S385
Protein: DP03297 (UniProt P01034)
Region: residues 27	to 37
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
N and C termini of the protein are disordered. This is particularly evident in the case of the N terminus (see Fig. 3) which is very flexible and tends to form a bent structure at the top of the Gly11‐Gly12 residues and the neighboring Pro13.
The relaxation data for 21 residues (first eight residues form N terminus included) were not collected due to signals overlap, intensive exchange with water, or low signal‐to‐noise ratio
There is a signal peptide of 26 residues, so there is a shift between UniProt numbering and the numbering in the article. Gly11 mentioned in the article corresponds to UniProt residue 37.
Cross-references: PDB:6RPV
BMRB:34399
Protein: DP03297 (UniProt P01034)
Region: residues 27	to 37
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
N and C termini of the protein are disordered. This is particularly evident in the case of the N terminus (see Fig. 3)
Cross-references: PDB:6ROA
Protein: DP03297 (UniProt P01034)
Region: residues 35	to 39
Annotation: limited proteolysis display site (Disorder function)
Evidence: combinatorial experimental and author inference evidence contained in single publication used in manual assertion
Supporting statements:
It is worth mentioning that the N-terminal segment of hCC is cleaved by cysteine proteases. In the case of hCC, cleavage takes place after Gly11 residue.
There is a signal peptide of 26 residues, so there is a shift between UniProt numbering and the numbering in the article. Gly11 mentioned in the article corresponds to UniProt residue 37.
Protein: DP03297 (UniProt P01034)
Region: residues 27	to 37
Annotation: molecular function inhibitor activity (Molecular function)
Evidence: combinatorial experimental and author inference evidence contained in single publication used in manual assertion
Supporting statements:
It is worth mentioning that the N-terminal segment of hCC is cleaved by cysteine proteases. In the case of hCC, cleavage takes place after Gly11 residue. The N-terminally truncated cystatin shows significantly decreased affinity toward cysteine proteases, which indicates that the N-terminal segment is necessary for the inhibitory activity.
There is a signal peptide of 26 residues, so there is a shift between UniProt numbering and the numbering in the article. Gly11 mentioned in the article corresponds to UniProt residue 37.
Protein: DP03298 (UniProt P63000)
Region: residues 182	to 192
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Intrinsically disordered C-terminal tail of Rac1.
Cross-references: PDB:5FI0
Protein: DP03298 (UniProt P63000)
Region: residues 179	to 192
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Intrinsically disordered C-terminal tail of Rac1.
Cross-references: PDB:1E96
Protein: DP03298 (UniProt P63000)
Region: residues 179	to 192
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Intrinsically disordered C-terminal tail of Rac1.
Cross-references: PDB:1I4D
PDB:1I4L
PDB:1I4T
Protein: DP03298 (UniProt P63000)
Region: residues 178	to 188
Annotation: protein binding (Molecular function)
Evidence: bait-prey hybrid interaction evidence used in manual assertion
Supporting statements:
The Rac1 C-terminal Domain Associates with Effector and Adapter Proteins
Using pull-down experiments followed by lipid kinase activity assays (23), we found that indeed the TAT-Rac1 C terminus (amino acids 178-188) bound PIP5K activity when used as a bait to fish in HL60 cell lysates (Fig. 4).
TAT-Rac1 also bound PIP5K in KG1a, MDCKII, and COS7 cells (data not shown). Apparently, the Rac1 178-188 region, encoded by the peptide used in this study, is already sufficient to mediate association of Rac1 with PIP5K.
We next examined the binding of the Rac1 peptide to other signaling proteins, implicated in cell migration and cell-cell adhesion. We found that the adapter proteins NCK and Crk bound specifically to the Rac1 C-terminal peptide.
Subsequently, using transient transfection of v-Crk mutants that were mutated in the SH2 or the N-terminal SH3 domain (27), we could show that the association of Crk with the Rac1 C terminus is mediated by the N-terminal SH3 domain of Crk and is not dependent on an intact SH2 domain (Fig. 5C).
Protein: DP03298 (UniProt P63000)
Region: residues 178	to 188
Annotation: molecular function regulator (Molecular function)
Evidence: experimental phenotypic evidence used in manual assertion
Supporting statements:
Apparently, both the effector loop and as the C terminus of Rac1 are required, in a non-redundant fashion, for growth factor-induced membrane ruffling and proper Rac1 localization.
The Rac1 C-terminal Domain Inhibits Actin Polymerization and Cell Migration
Protein: DP03298 (UniProt P63000)
Region: residues 184	to 188
Annotation: protein binding (Molecular function)
Evidence: mutant phenotype evidence used in manual assertion
Supporting statements:
Having established at least two signaling proteins that associate directly with the Rac1 C terminus, we tested whether these interactions would involve identical residues within the Rac1 C-terminal sequence. To this end, two mutants of the TAT-Rac1 C-terminal peptide were synthesized. In the first one, the three prolines (amino acids 179-181) were replaced by alanine residues (Rac1 PPP-AAA). In the second, the RKR sequence (amino acids 185-187) was replaced by alanine residues (Rac1 RKR-AAA) (Fig. 6A). The interaction of the Rac1 C terminus with PIP5K was shown previously (28) to be mediated by basic amino acids, in particular Lys-186. In line with these data, the TAT-Rac1 RKR-AAA peptide no longer associated with PIP5K activity in the pull-down assay (Fig. 6B).
These data establish the presence of two binding motifs for signaling proteins within the Rac1 C terminus.
Protein: DP03298 (UniProt P63000)
Region: residues 178	to 182
Annotation: protein binding (Molecular function)
Evidence: mutant phenotype evidence used in manual assertion
Supporting statements:
Having established at least two signaling proteins that associate directly with the Rac1 C terminus, we tested whether these interactions would involve identical residues within the Rac1 C-terminal sequence. To this end, two mutants of the TAT-Rac1 C-terminal peptide were synthesized. In the first one, the three prolines (amino acids 179-181) were replaced by alanine residues (Rac1 PPP-AAA). In the second, the RKR sequence (amino acids 185-187) was replaced by alanine residues (Rac1 RKR-AAA) (Fig. 6A).
Because the interaction with the Crk adapter protein involved the Crk SH3 domain, we tested whether the three consecutive prolines in the Rac1 C terminus mediated Crk binding. When using the Rac1 PPP-AAA peptide, the binding to Crk was abolished, confirming that these prolines were required for the interaction (Fig. 6C).
These data establish the presence of two binding motifs for signaling proteins within the Rac1 C terminus.
Protein: DP03298 (UniProt P63000)
Region: residues 184	to 188
Annotation: localization (Biological process)
Evidence: fluorescence microscopy evidence used in manual assertion
Supporting statements:
Next, the wild type and the two mutant peptides were used to determine the relation between the presence of either binding site and localization and effects of the peptides. Phosphatidylinositol 4,5-biphosphate, a product of PIP5K, is present in lipid rafts from where actin polymerization is mediated (29, 30). In line with this, the wild type Rac1 C terminus co-localized with lipid rafts in HL60 cells (Fig. 7A), suggesting that the inhibitory effect of this peptide on in vitro migration is because of interference with localized PIP5K/phosphatidylinositol 4,5-biphosphate-dependent, Rac-mediated signaling.
The Rac1 PPP-AAA peptide also localized to lipid rafts; the Rac1 RKR-AAA peptide showed less prominent co-localization with lipid rafts, suggesting that the basic motif in the C terminus is involved, perhaps via PIP5K, in mediating associations with raft-resident proteins.
In MDCKII cells, the Rac1 C terminus showed a clear localization to both cell-cell junctions and peripheral membranes (Fig. 7B). The peptide did not associate to endomembranes or to the nuclear membrane. This localization was mimicked by the Rac1 PPP-AAA peptide, but the Rac1 RKR-AAA peptide showed a marked loss of accumulation at peripheral membranes.
The Rac1 RKR-AAA peptide no longer inhibited HGF-induced membrane ruffling, whereas the Rac1 PPP-AAA peptide did (Fig. 7C). This suggests that the RKR sequence in the Rac1 C terminus controls membrane ruffling and Rac1-localization to these ruffles, possibly through the association with PIP5K.
These data further underscore the relationship between the amino acid sequence of the C-terminal domain of Rho-like GTPases and their intracellular targeting and suggests that binding partners for Rac1 are also differentially distributed over distinct regions of the plasma membrane (i.e. cell-cell junctions versus peripheral plasma membrane).
Protein: DP03298 (UniProt P63000)
Region: residues 184	to 188
Annotation: molecular function regulator (Molecular function)
Evidence: experimental phenotypic evidence used in manual assertion
Supporting statements:
Finally, the different Rac1 peptides were characterized for their effects on SDF-1-induced actin polymerization and chemotaxis. The Rac1 PPP-AAA peptide efficiently blocked SDF-1-induced actin polymerization, whereas the Rac1 RKR-AAA peptide did not (Fig. 7E). Similarly, the Rac1 RKR-AAA peptide no longer interfered significantly with SDF-1-induced chemotaxis of HL60 cells. In contrast, the PPP-AAA mutant peptide inhibited migration as efficiently as the wild type peptide (Fig. 7F). This indicates that, in addition to the Crk binding proline-rich motif, it is primarily the basic, PIP5K binding motif that contributes to the control of actin polymerization and cell migration by Rac1.
Protein: DP03299 (UniProt P00734)
Region: residues 187	to 211
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The construct (residues 45–579) can be traced in the electron density map almost in its entirety (Fig. 1), except for two disordered regions connecting the two kringles (residues 144–168) and kringle-2 to the A chain (residues 255–273).
The linker connecting the two kringles is 26 residues long, from Gly-144 to Gln-169, and completely disordered.
The residue numbering of the article refers to the residues of the prothrombin chain that lacks the first 43 residues (signal peptide + propeptide) of the respective UniProt entry.
Cross-references: PDB:4HZH
Protein: DP03299 (UniProt P00734)
Region: residues 298	to 316
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The construct (residues 45–579) can be traced in the electron density map almost in its entirety (Fig. 1), except for two disordered regions connecting the two kringles (residues 144–168) and kringle-2 to the A chain (residues 255–273).
There are no direct interactions between fragment 2 and the A chain, and 20 residues are missing from the highly acidic linker connecting these domains.
The residue numbering of the article refers to the residues of the prothrombin chain that lacks the first 43 residues (signal peptide + propeptide) of the respective UniProt entry.
Cross-references: PDB:4HZH
Protein: DP03299 (UniProt P00734)
Region: residues 298	to 316
Annotation: flexible linker (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The construct (residues 45–579) can be traced in the electron density map almost in its entirety (Fig. 1), except for two disordered regions connecting the two kringles (residues 144–168) and kringle-2 to the A chain (residues 255–273).
The residue numbering of the article refers to the residues of the prothrombin chain that lacks the first 43 residues (signal peptide + propeptide) of the respective UniProt entry.
The linker connecting the two kringles is 26 residues long, from Gly-144 to Gln-169, and completely disordered.
Cross-references: PDB:4HZH
Protein: DP03299 (UniProt P00734)
Region: residues 187	to 211
Annotation: flexible linker (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The construct (residues 45–579) can be traced in the electron density map almost in its entirety (Fig. 1), except for two disordered regions connecting the two kringles (residues 144–168) and kringle-2 to the A chain (residues 255–273).
The residue numbering of the article refers to the residues of the prothrombin chain that lacks the first 43 residues (signal peptide + propeptide) of the respective UniProt entry.
There are no direct interactions between fragment 2 and the A chain, and 20 residues are missing from the highly acidic linker connecting these domains.
Cross-references: PDB:4HZH
Protein: DP03299 (UniProt P00734)
Region: residues 90	to 110
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
After molecular replacement of the Gla-domainless prothrombin structure using the coordinates 3NXP of prethrombin-1, extra electron density was clearly detected to assign fragment 1 with confidence from Gly-68 to Cys-143, covering kringle-1 (Cys-65 to Cys-143) almost entirely.
The residue numbering of the article refers to the residues of the prothrombin chain that lacks the first 43 residues (signal peptide + propeptide) of the respective UniProt entry.
Cross-references: PDB:4HZH
Protein: DP03299 (UniProt P00734)
Region: residues 187	to 211
Annotation: flexible linker (Disorder function)
Evidence: fluorescence resonance energy transfer evidence used in manual assertion
Supporting statements:
The significant variation in the distance between residues 101 in kringle-1 and residue 210 in kringle-2 detected by LRET measurements is caused by the intrinsic flexibility of the connecting linker between the two kringles that appears as disordered in the crystal structure.
The residue numbering of the article refers to the residues of the prothrombin chain that lacks the first 43 residues (signal peptide + propeptide) of the respective UniProt entry.
Cross-references: PDB:4HZH
Protein: DP03299 (UniProt P00734)
Region: residues 187	to 211
Annotation: disorder (Structural state)
Evidence: fluorescence resonance energy transfer evidence used in manual assertion
Supporting statements:
The significant variation in the distance between residues 101 in kringle-1 and residue 210 in kringle-2 detected by LRET measurements is caused by the intrinsic flexibility of the connecting linker between the two kringles that appears as disordered in the crystal structure.
The residue numbering of the article refers to the residues of the prothrombin chain that lacks the first 43 residues (signal peptide + propeptide) of the respective UniProt entry.
Cross-references: PDB:4HZH
Protein: DP03299 (UniProt P00734)
Region: residues 301	to 316
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
All domains of ProTΔ146–167 are clearly resolved in the electron density map, except for several residues of Lnk3. The important cleavage site at R271 is contained in this segment and has so far eluded X-ray detection in all published structures of human GD-ProT (15), prethrombin-1 (17) or meizothrombin desF1 (16). Disorder in this region supports the conclusion that R271 is constitutively exposed to solvent for proteolytic attack, regardless of the conformation of Lnk2.
The residue numbering of the article refers to the residues of the prothrombin chain that lacks the first 43 residues (signal peptide + propeptide) of the respective UniProt entry.
Cross-references: PDB:4O03
PDB:4NZQ
Protein: DP03299 (UniProt P00734)
Region: residues 312	to 316
Annotation: limited proteolysis display site (Disorder function)
Evidence: combinatorial experimental and author inference evidence contained in single publication used in manual assertion
Supporting statements:
All domains of ProTΔ146–167 are clearly resolved in the electron density map, except for several residues of Lnk3. The important cleavage site at R271 is contained in this segment and has so far eluded X-ray detection in all published structures of human GD-ProT (15), prethrombin-1 (17) or meizothrombin desF1 (16). Disorder in this region supports the conclusion that R271 is constitutively exposed to solvent for proteolytic attack, regardless of the conformation of Lnk2
The residue numbering of the article refers to the residues of the prothrombin chain that lacks the first 43 residues (signal peptide + propeptide) of the respective UniProt entry. Therefore the known cleavage site mentioned by the authors (R271) corresponds to R314 in the UniProt sequence.
Cross-references: PDB:4O03
PDB:4NZQ
Protein: DP03300 (UniProt P31749)
Region: residues 114	to 144
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Missing electron density region of AKT1 corresponding to the interdomain linker connecting the PH and Kinase domains.
Cross-references: PDB:3O96
Protein: DP03300 (UniProt P31749)
Region: residues 114	to 144
Annotation: flexible linker (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Missing electron density region of AKT1 corresponding to the interdomain linker connecting the PH and Kinase domains.
Cross-references: PDB:3O96
Protein: DP03301 (UniProt P09237)
Region: residues 18	to 28
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
These coordi-nates differ from the free form with a backbone RMSD of 1.6 A ̊across the catalytic domain and 2.1 A ̊across the pro-domain (omitting the disordered segments listed inTable 1)
Residue ranges used: 12–27, 31–72, 83–216, and 224–238. Uncertainties are SDs
The segments between the residues here indicated are the disordered regions (1-11, 28-30, 73-82, 217-223 and 239-250), corresponding to regions  18-28, 45-47, 90-99, 234-240 and 256-267 on the original protein sequence
Cross-references: PDB:2MZH
PDB:2MZI
PDB:2MZE
Protein: DP03301 (UniProt P09237)
Region: residues 90	to 99
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
These coordi-nates differ from the free form with a backbone RMSD of 1.6 A ̊across the catalytic domain and 2.1 A ̊across the pro-domain (omitting the disordered segments listed inTable 1)
Residue ranges used: 12–27, 31–72, 83–216, and 224–238. Uncertainties are SDs
The segments between the residues here indicated are the disordered regions (1-11, 28-30, 73-82, 217-223 and 239-250), corresponding to regions  18-28, 45-47, 90-99, 234-240 and 256-267 on the original protein sequence
Cross-references: PDB:2MZH
PDB:2MZI
PDB:2MZE
Protein: DP03301 (UniProt P09237)
Region: residues 256	to 267
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
These coordi-nates differ from the free form with a backbone RMSD of 1.6 A ̊across the catalytic domain and 2.1 A ̊across the pro-domain (omitting the disordered segments listed inTable 1)
Residue ranges used: 12–27, 31–72, 83–216, and 224–238. Uncertainties are SDs
The segments between the residues here indicated are the disordered regions (1-11, 28-30, 73-82, 217-223 and 239-250), corresponding to regions  18-28, 45-47, 90-99, 234-240 and 256-267 on the original protein sequence
Cross-references: PDB:2MZH
PDB:2MZI
PDB:2MZE
Protein: DP03301 (UniProt P09237)
Region: residues 90	to 99
Annotation: disorder to order (Structural transition)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
In concert with removal of auto-inhibition, bicelles introduce large peaks shifts (Figure S1A) and NOEs to theGlu74-Asn80 region that imply its change from disorder in the free state to formation of an ordered hairpin (Figure S6). 
The segments between the residues here indicated are the disordered regions (1-11, 28-30, 73-82, 217-223 and 239-250), corresponding to regions  18-28, 45-47, 90-99, 234-240 and 256-267 on the original protein sequence
Cross-references: PDB:2MZH
PDB:2MZI
PDB:2MZE
Protein: DP03301 (UniProt P09237)
Region: residues 21	to 40
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Also consistent with the hypothesis of distortion, the N-terminal 20 residues appear more disordered with heparin dp8 bound (Figures 6A and 6B)
Heparin dp8 may enhance disorder near the N terminus (Figure 6A) and appears to recruit the basic and dynamic C terminus a significant distance to the binding site on the back of the catalytic domain (Figure 6D), perhaps facilitating maturation (Figure 3)
The protein sequence here described starts on residue 21