LiteFold/DisProt huggingface dataset:
Protein: DP03529 (UniProt Q9NP98)
Region: residues 106	to 128
Annotation: actinin binding (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
We could not fully assign Δ91-FATZ-1 due to fast relaxation of cross-peaks in the region comprising residues 177 to 291. We could, however, locate the α-actinin-2–interacting region within the CTR at residues 176 to 292, as the corresponding cross-peaks disappeared or showed a drop in signal intensity (Fig. 2J and fig. S5B). We found a similar signal reduction pattern and thus binding behavior for both α-actinin-2 and hd-α-actinin-2. Further, a decrease in signal intensity upon binding to α-actinin-2 around residues 106 and 128, mapping to the GRR, indicated additional binding site(s) apart from the interacting region found within the CTR, which is in line with ITC and peptide array data (Fig. 2K and figs. S6 and S7).
Protein: DP03529 (UniProt Q9NP98)
Region: residues 180	to 199
Annotation: actinin binding (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
In both α-actinin-2/FATZ-1 structures, one can see two identical stretches of amino acids bound to α-actinin-2, which are conserved among FATZ proteins (62 and 71% average identity for LM1 and LM2, respectively) and conform to the definition of eukaryotic linear motifs (ELMs) (Fig. 3, A and B) (36, 37). Accordingly, they are hereafter called LM1 (residues 180 to 199) and LM2 (residues 216 to 240). 
Cross-references: PDB:7A8T
Protein: DP03529 (UniProt Q9NP98)
Region: residues 216	to 240
Annotation: actinin binding (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
In both α-actinin-2/FATZ-1 structures, one can see two identical stretches of amino acids bound to α-actinin-2, which are conserved among FATZ proteins (62 and 71% average identity for LM1 and LM2, respectively) and conform to the definition of eukaryotic linear motifs (ELMs) (Fig. 3, A and B) (36, 37). Accordingly, they are hereafter called LM1 (residues 180 to 199) and LM2 (residues 216 to 240). 
Cross-references: PDB:7A8T
Protein: DP03529 (UniProt Q9NP98)
Region: residues 200	to 215
Annotation: flexible linker (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
LM1 and LM2 are connected by a short 16- and 13-residue linker in rod-α-actinin-2/mini-FATZ-1 and hd-α-actinin-2/Δ91-FATZ-1, respectively, which is not visible in electron density maps and matches the positions of previously identified cross-links (Fig. 3A and fig. S9B).
Cross-references: PDB:7A8T
Protein: DP03529 (UniProt Q9NP98)
Region: residues 200	to 215
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
LM1 and LM2 are connected by a short 16- and 13-residue linker in rod-α-actinin-2/mini-FATZ-1 and hd-α-actinin-2/Δ91-FATZ-1, respectively, which is not visible in electron density maps and matches the positions of previously identified cross-links (Fig. 3A and fig. S9B).
Cross-references: PDB:7A8T
Protein: DP03529 (UniProt Q9NP98)
Region: residues 216	to 240
Annotation: actinin binding (Molecular function)
Evidence: isothermal titration calorimetry evidence used in manual assertion
Supporting statements:
To dissect the contribution of LM1 and LM2 to the binding affinity, we used ITC with one peptide corresponding to each motif. While we could not detect binding between LM1 peptide and α-actinin-2 (Fig. 3D), LM2 peptide bound to α-actinin-2 with a binding stoichiometry of 1.9 and a Kd of 315 nM (Fig. 3E), which fits that of Δ91-FATZ-1–binding to hd-α-actinin-2 (Kd = 260 nM; see table S3).
Protein: DP03529 (UniProt Q9NP98)
Region: residues 218	to 228
Annotation: actinin binding (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
These diverse binding affinities match the structure of rod-α-actinin-2/Δ91-FATZ-1, which was additionally crystallized and displays only a shorter LM2 bound to α-actinin-2 rod [see fig. S10, A (right) and D, and table S4), revealing LM2 as the major binding site. 
Cross-references: PDB:7A8U
Protein: DP03529 (UniProt Q9NP98)
Region: residues 92	to 299
Annotation: molecular condensate scaffold activity (Molecular function)
Evidence: differential interference contrast microscopy evidence used in manual assertion
Supporting statements:
Only Δ91-FATZ-1 showed spontaneous condensation (i.e., increased turbidity) when the temperature was increased from 4° to 22° or 37°C, whereas N-FATZ-1 remained transparent (Fig. 5C and fig. S16A). Δ91-FATZ-1 formed round-shaped droplets that were constantly fusing over time and reached up to 20 μm in diameter, as indicated by differential interference contrast (DIC) microscopy (see Fig. 5C, fig. S16B, and movie S4).
Protein: DP03530 (UniProt P19554)
Region: residues 39	to 81
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
The spectrum obtained in detergent-free buffer showed a pronounced minimum at 199 nm indicative of a predominantly unordered protein.
Protein: DP03530 (UniProt P19554)
Region: residues 39	to 51
Annotation: lipid binding (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Continuous stretches with prominent chemical shift changes were observed for residues 39–51 and 64–78. In contrast, amide chemical shifts of residues 52–63 were virtually unaffected by the presence of DPC micelles.
Cross-references: BMRB:15513
PDB:2K7Y
Protein: DP03530 (UniProt P19554)
Region: residues 64	to 78
Annotation: lipid binding (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Continuous stretches with prominent chemical shift changes were observed for residues 39–51 and 64–78. In contrast, amide chemical shifts of residues 52–63 were virtually unaffected by the presence of DPC micelles.
Cross-references: BMRB:15513
PDB:2K7Y
Protein: DP03530 (UniProt P19554)
Region: residues 39	to 48
Annotation: disorder to order (Structural transition)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
In contrast, characteristic secondary shifts of VpUcyt observed in the presence of 100 mm DPC clearly indicated the formation of two helices (Fig. 3, right column).
On the basis of the three sets of secondary shift data in Fig. 3 (right), the helices probably range from I39 to E48 (helix 2) and from L64 to R70 (helix 3).
The fractional helicity of amino acid stretches 39–48 (helix 2) and 64–70 (helix 3) was estimated by comparing the observed average secondary shifts with the values expected for a regular helix. This procedure provided fractional helicities of ∼ 80% (Δδ13Cα) for helix 2 and 40% (Δδ1Hα) for helix 3.
Cross-references: BMRB:15513
PDB:2K7Y
Protein: DP03530 (UniProt P19554)
Region: residues 39	to 48
Annotation: order (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
In contrast, characteristic secondary shifts of VpUcyt observed in the presence of 100 mm DPC clearly indicated the formation of two helices (Fig. 3, right column).
The fractional helicity of amino acid stretches 39–48 (helix 2) and 64–70 (helix 3) was estimated by comparing the observed average secondary shifts with the values expected for a regular helix. This procedure provided fractional helicities of ∼ 80% (Δδ13Cα) for helix 2 and 40% (Δδ1Hα) for helix 3.
Cross-references: BMRB:15513
PDB:2K7Y
Protein: DP03530 (UniProt P19554)
Region: residues 39	to 81
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
VpUcyt appears to be unstructured in buffer.
Protein: DP03530 (UniProt P19554)
Region: residues 39	to 51
Annotation: plasma membrane (Cellular component)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Continuous stretches with prominent chemical shift changes were observed for residues 39–51 and 64–78.
We propose that the structure of micelle-associated VpUcyt is a reasonable approximation of the physiologically relevant membrane-attached cytoplasmic region of VpU. This view is supported by the experimentally confirmed location of VpUcyt at the micelle–water interface. The polar headgroup of DPC is chemically identical to that of the large fraction of phospholipids in biological membranes that feature a phosphatidylcholine headgroup.
Cross-references: BMRB:15513
Protein: DP03530 (UniProt P19554)
Region: residues 64	to 78
Annotation: plasma membrane (Cellular component)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Continuous stretches with prominent chemical shift changes were observed for residues 39–51 and 64–78.
We propose that the structure of micelle-associated VpUcyt is a reasonable approximation of the physiologically relevant membrane-attached cytoplasmic region of VpU. This view is supported by the experimentally confirmed location of VpUcyt at the micelle–water interface. The polar headgroup of DPC is chemically identical to that of the large fraction of phospholipids in biological membranes that feature a phosphatidylcholine headgroup.
Cross-references: BMRB:15513
Protein: DP03531 (UniProt P49789)
Region: residues 107	to 127
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Though it is possible to ‘‘refine’’ the models to working R factors below 20%, the structural models presented herein have good geometry and are at apparent free R-factor minima, values of which are likely limited by disorder that prevents modeling of residues 107–128.
The Fhit–IB2 structures, like those of the first Fhit structures, contains an amino-terminal b-hairpin not found in Hint and a gap from residue 107 to residue 127 or to 128 that is disordered (Fig. 2).
Residues 107-127 are disordered in all structures.
Cross-references: PDB:2FHI
PDB:1FHI
Protein: DP03531 (UniProt P49789)
Region: residues 112	to 116
Annotation: phosphorylation display site (Disorder function)
Evidence: mass spectrometry evidence used in manual assertion
Supporting statements:
Our data demonstrate that Fhit is a target of tyrosine phosphorylation by the Src protein kinase. We show that Src phosphorylates Y114 of Fhit in vitro and in vivo, providing insight into a biochemical pathway involved in Fhit signaling.
Here we report that Fhit is a target of tyrosine phosphorylation by Src protein kinase. We show that Src phosphorylates Y114 of Fhit in vitro and in vivo and therefore provide important clues to biochemical mechanisms involved in Fhit signaling.
To identify which tyrosine is phosphorylated, a trypsin digest of fraction 3 was analyzed by HPLC-ion-trap mass spectrometry. Only peptide 110-119 was phosphorylated, and the fragmentation pattern of the peptide was compatible only with Y114 being phosphorylated and not S112 (Fig. 3E).
Thus, the mass spectrometry data demonstrated that fraction 3 is Fhit phosphorylated on Y114 on both subunits.
The data clearly show that Fhit is phosphorylated on tyrosine 114 by Src kinase both in vitro and in vivo.
Protein: DP03531 (UniProt P49789)
Region: residues 112	to 116
Annotation: phosphorylation display site (Disorder function)
Evidence: mutant phenotype evidence used in manual assertion
Supporting statements:
Our data demonstrate that Fhit is a target of tyrosine phosphorylation by the Src protein kinase. We show that Src phosphorylates Y114 of Fhit in vitro and in vivo, providing insight into a biochemical pathway involved in Fhit signaling.
Here we report that Fhit is a target of tyrosine phosphorylation by Src protein kinase. We show that Src phosphorylates Y114 of Fhit in vitro and in vivo and therefore provide important clues to biochemical mechanisms involved in Fhit signaling.
To determine which tyrosine is phosphorylated in vivo by Src, several Fhit mutants were created, FhitY114F, FhitY145F and FhitY114F, Y145F, individually cotransfected with the activated SRC construct, and checked for tyrosine phosphorylation by Western blotting. Phosphorylated Fhit was detected on expression of WT Fhit or FhitY145F (Fig. 4B Top, lanes 2 and 4) but not FhitY114F or FhitY114F, Y145F (Fig. 4B Top, lanes 3 and 5). The tyrosine phosphorylation was confirmed by using antiphosphotyrosine antibody (Fig. 4B Bottom). These results confirmed that Y114 of Fhit is a target of Src phosphorylation in vivo.
The data clearly show that Fhit is phosphorylated on tyrosine 114 by Src kinase both in vitro and in vivo.
Protein: DP03532 (UniProt Q68J44)
Region: residues 2	to 31
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Residues 2–31 in the N-terminal region and residues 207–220 in the C-terminal tail were not visible in the electron-density maps and thus were not included in the model.
Residues 2-31 and 207-220 are missing in all chains and are presumably disordered.
Cross-references: PDB:2Y96
Protein: DP03532 (UniProt Q68J44)
Region: residues 207	to 220
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Residues 2–31 in the N-terminal region and residues 207–220 in the C-terminal tail were not visible in the electron-density maps and thus were not included in the model.
Residues 2-31 and 207-220 are missing in all chains and are presumably disordered.
Cross-references: PDB:2Y96
Protein: DP03533 (UniProt O95147)
Region: residues 2	to 23
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 2–23 of DUSP14, suggesting that this region of the protein is disordered.
Cross-references: PDB:2WGP
Protein: DP03534 (UniProt P12520)
Region: residues 1	to 17
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with high relative B-factor values used in manual assertion
Supporting statements:
Four structural motifs important for Vpr's interaction with partners are discernible: a random-coil N-terminal tail; a hydrophobic cleft formed by helices α1, α2 and the first turn of α3; the loop connecting α2 and α3 (insert loop); and the C-terminal region of helix α3 (Supplementary Fig. 2a).
The PDB has low resolution in the N-terminal tail and the figure shows the disorder of this region of Vpr.
Cross-references: PDB:5JK7
Protein: DP03534 (UniProt P12520)
Region: residues 1	to 17
Annotation: protein binding (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
Vpr interacts with DCAF1 by using its N terminus and helix α3 (described below) and interacts with UNG2 via the insert loop and residues in the hydrophobic cleft, burying a surface area of 1,650 Å2 and 940 Å2, respectively (Supplementary Fig. 2b).
(c) Detailed view of the interaction between the N-terminal tail of Vpr and residues of DCAF1 at the edges of two propeller blades. 
Cross-references: PDB:5JK7
Protein: DP03535 (UniProt P69697)
Region: residues 1	to 86
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
The CD value at 222 nm of the zinc-free Tat was closer to zero than that of the zinc-bound form. Moreover, a negative peak at ∼202 nm, which is an index of the presence of random-coil structures, is more prominent upon removal of zinc ions.
Authors claim the use of the isolate HXB2 however the sequence they report in Figure 1. corresponds to this Uniprot.
Protein: DP03535 (UniProt P69697)
Region: residues 1	to 86
Annotation: pre-molten globule (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
The CD spectrum of the zinc-bound Tat had a minimum at 202 nm and a CD value close to zero at 222 nm, indicating that Tat is largely disordered (Fig. 2A). However, a slightly negative shoulder around 222 nm suggests the presence of residual helical structures. 
Therefore, the structure of zinc-bound Tat at neutral pH corresponds to a pre-molten globule state.
Authors claim the use of the isolate HXB2 however the sequence they report in Figure 1. corresponds to this Uniprot.
Protein: DP03535 (UniProt P69697)
Region: residues 1	to 86
Annotation: pre-molten globule (Structural state)
Evidence: small-angle X-ray scattering evidence used in manual assertion
Supporting statements:
The absence of a peak in the Kratky plot of the zinc-bound Tat indicates largely disordered structures (Fig. 3B). However, the presence of a plateau without a linear increase in wide-angle regions suggests that the protein molecule is not completely unfolded [24].
Comparison of the scaling curves with the Rg of Tat shows that the molecular size of Tat is close to but slightly more compact than the fully unfolded state.
Authors claim the use of the isolate HXB2 however the sequence they report in Figure 1. corresponds to this Uniprot.
Protein: DP03535 (UniProt P69697)
Region: residues 1	to 86
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The one-dimensional 1H NMR spectrum of the zinc-bound Tat showed line broadening due to conformational dynamics in the intermediate exchange regime (Fig. 2B), suggesting structural fluctuation in millisecond time scales.
Authors claim the use of the isolate HXB2 however the sequence they report in Figure 1. corresponds to this Uniprot.
Protein: DP03535 (UniProt P69697)
Region: residues 1	to 86
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
The pH titration of CD spectra at pH values from 7 to 4 showed that the ellipticity at 222 nm increased with decreasing pH and exhibited a cooperative helix unfolding transition around pH 5–5.5 (Fig. 4A and B). The CD spectra below pH 5 were coincident with that of zinc-free Tat (Fig. 2, Fig. 4A,B), indicating that both the decrease in pH and the removal of zinc ions have identical effects on the secondary structure of Tat.
Taken together, the results indicate that Tat at pH 4 is in a random coil-like fully unfolded state.
Authors claim the use of the isolate HXB2 however the sequence they report in Figure 1. corresponds to this Uniprot.
Protein: DP03535 (UniProt P69697)
Region: residues 1	to 86
Annotation: disorder to pre-molten globule (Structural transition)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
These results indicate that Tat loses residual helices, which were present in the zinc-bound form, and turns into disordered structures upon removal of zinc ions.
Authors claim the use of the isolate HXB2 however the sequence they report in Figure 1. corresponds to this Uniprot.
Protein: DP03535 (UniProt P69697)
Region: residues 1	to 86
Annotation: metal ion binding (Molecular function)
Evidence: mass spectrometry evidence used in manual assertion
Supporting statements:
The ICP-MS measurement revealed that 59.2 ± 0.8 μM zinc ions were present in 25.0 ± 0.2 μM Tat, indicating that the concentration ratio of Tat to zinc ions was 1:2.
Authors claim the use of the isolate HXB2 however the sequence they report in Figure 1. corresponds to this Uniprot.
Protein: DP03536 (UniProt Q05318)
Region: residues 1306	to 1593
Annotation: disorder (Structural state)
Evidence: electron microscopy evidence used in manual assertion
Supporting statements:
We favor the hypothesis that CRV (residues 1,069–1,305) constitutes the globule and that the variable region between CRV and CRVI (1,306–1,593) constitutes a largely unstructured hinge region that is not readily discernible by negative stain EM.
Protein: DP03536 (UniProt Q05318)
Region: residues 1306	to 1593
Annotation: flexible linker (Disorder function)
Evidence: electron microscopy evidence used in manual assertion
Supporting statements:
We favor the hypothesis that CRV (residues 1,069–1,305) constitutes the globule and that the variable region between CRV and CRVI (1,306–1,593) constitutes a largely unstructured hinge region that is not readily discernible by negative stain EM.
Protein: DP03536 (UniProt Q05318)
Region: residues 1306	to 1593
Annotation: RNA polymerase activity (Molecular function)
Evidence: quantitative western immunoblotting evidence used in manual assertion
Supporting statements:
To test whether the bulk of the U region might nonetheless function as a linker, we engineered five additional L protein constructs, each containing an in-frame EGFP insertion at different positions spanning the U segment (positions 1318, 1374, 1472, 1522, and 1577) and assessed effects on polymerase activity along with the wt and the previous construct with the EGFP insertion at position 1595. Surprisingly, none of the newly constructed L-EGFP variants displayed any polymerase activity (Fig. 6). As noted previously for the 1595 construct, all L-EGFP proteins accumulated to levels somewhat lower than the wt, but the reduction was particularly dramatic for the 1522 mutant, which reproducibly accumulated about 10-fold less L protein (Fig. 6), an amount nonetheless sufficient for concluding lack of significant polymerase activity.
Taken together, these findings strongly suggest that the bulk of the U domain does not simply represent an unstructured region between C and M domains but more likely serves some other role in polymerase function.
Protein: DP03537 (UniProt Q05320)
Region: residues 524	to 539
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
As shown in Fig. 1A, the peptide assumes a random-coil conformation in aqueous buffer and a more defined structure in the presence of SDS micelles, where it displays a typical helical structure.
Protein: DP03537 (UniProt Q05320)
Region: residues 524	to 539
Annotation: order (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
As shown in Fig. 1A, the peptide assumes a random-coil conformation in aqueous buffer and a more defined structure in the presence of SDS micelles, where it displays a typical helical structure.
Protein: DP03537 (UniProt Q05320)
Region: residues 524	to 539
Annotation: disorder to order (Structural transition)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
As shown in Fig. 1A, the peptide assumes a random-coil conformation in aqueous buffer and a more defined structure in the presence of SDS micelles, where it displays a typical helical structure.
Protein: DP03537 (UniProt Q05320)
Region: residues 524	to 539
Annotation: lipid binding (Molecular function)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
As shown in Fig. 1A, the peptide assumes a random-coil conformation in aqueous buffer and a more defined structure in the presence of SDS micelles, where it displays a typical helical structure.
Protein: DP03537 (UniProt Q05320)
Region: residues 524	to 539
Annotation: disorder (Structural state)
Evidence: fluorescence evidence used in manual assertion
Supporting statements:
Fluorescence emission in the absence of SDS shows a maximum emission wavelength of ∼337 nm (Fig. 1B). This maximum reflects the tryptophan accessibility and the peptide aggregation because of its high hydrophobicity and random structure.