Intrinsic Disorder in Proteins with Pathogenic Repeat Expansions
Abstract
:1. Introduction
2. Polyalanine Repeat Expansions
2.1. Molecular Mechanisms of Poly-Ala Expansion Diseases
2.2. Genes Associated with Poly-Ala Expansion Diseases
3. Poly-Glutamine Repeat Expansions
3.1. Molecular Mechanisms of PolyQ Repeat Expansion Diseases
3.2. Genes Associated with PolyQ Expansion Diseases
4. Non-Coding Region Repeat Expansion
4.1. Molecular Mechanisms of Diseases Associated with Non-Coding Region Repeat Expansions
4.2. Genes Associated with Non-Coding Region Repeat Expansions
5. Intrinsic Disorder in Proteins Associated with Pathological Repeat Expansions
5.1. Disorder in Proteins Associated with Poly-Ala Expansion Diseases
5.2. Disorder in Proteins Associated with PolyQ Expansion Diseases
5.3. Disorder in Proteins Associated with Non-Coding Region Repeat Expansions
6. Summary
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Repeat Location | Gene | Disease a | Repeat Sequence | WT Length | Pathogenic Length b | % Disorder c | References | |
---|---|---|---|---|---|---|---|---|
Poly-alanine | Exon | HOXD13 | SPD II | GCG | 15 | >21 | 33.82 | [64,65,66] |
Exon | HOXA13 | HFGS | GCG | 12 | >17 | 34.28 | [67] | |
Exon | RUNX2 | CCD | GCG | 17 | >26 | 62.96 | [65,68] | |
Exon | ZIC2 | HPE | GCG | 9 | -- | 54.89 | [69,70] | |
Exon | PHOX2B | CCHS | GCG | 20 | -- | 54.15 | [71,72,73] | |
Exon-X chrom. | SOX3 | XLMR + GHD | GCG | 15 | >25 | 51.12 | [74,75] | |
Exon-X chrom. | ARX | XLMR | GCG | 16 | >17, >22 | 59.07 | [76,77] | |
Exon | FOXL2 | BPEIS | GCG | 14 | >21, >24 | 47.34 | [78,79] | |
Exon | PABPN1 | OPMD | GCG | 10 | >11, >16 | 59.80 | [80,81] | |
Poly-glutamine | Exon | KCNN3 | Schizo. d | CAG | -- | -- | 37.50 | [82] |
Exon | JPH3 | HDL2 | CAG/CTG | 6 to 28 | >41 | 51.07 | [83,84,85] | |
Exon | HTT | HD | CAG | 6 to 35 | >35 | 19.10 | [86,87] | |
Exon | ATN1 | DRPLA | CAG | 3 to 36 | >48 | 86.05 | [88,89] | |
Exon | AR | SBMA | CAG | 9 to 36 | >37 | 54.13 | [90] | |
Exon | ATXN1 | SCA1 | CAG | 6 to 39 | >39 | 54.97 | [91] | |
Exon | ATXN2 | SCA2 | CAG | 14 to 32 | >33 | 79.13 | [92,93] | |
Exon | ATXN3 | SCA3 | CAG | 12 to 40 | >54 | 42.03 | [82,94] | |
Exon | CACNA1A | SCA6 | CAG | 4 to 18 | >20 | 42.08 | [95,96] | |
Exon | ATXN7 | SCA7 | CAG | 7 to 17 | >33 | 71.30 | [97,98] | |
Exon | TBP | SCA17 | CAG | 25 to 42 | >44 | 46.31 | [99,100] | |
Non-coding | 5′ UTR | PPP2R2B | SCA12 | CAG | 7 to 32 | >54 | 7.67 | [101,102] |
5′ UTR-X chrom. | FMR1 | FXMR, FXTAS | CGG | 6 to 55 | >200, >55 | 38.29 | [103] | |
5′ UTR | DIP2B | FRA12A MR | CGG | 6 to 23 | >200 | 19.73 | [104] | |
5′ UTR-X chrom. | FMR2 | FRAXE MR | GCC | -- | >200 | 58.12 | [105,106,107] | |
5′ UTR | C9orf72 | C9ALS/FTD | GGGGCC | -- | Unknown | 2.70 | [108,109] | |
Intron | FXN | FRDA | GAA | 7 to 22 | >66 | 40.00 | [110,111] | |
Intron | CNBP/zfn9 | DM2 | CCTG | <27 | >75 | 19.77 | [112,113] | |
Intron | ATXN10 | SCA10 | ATTCT | 10 to 29 | >279 | 5.26 | [114,115] | |
Intron | NOP56 | SCA36 | GGCCTG | 3 to 8 | >1500 | 26.26 | [116] | |
Intron | TCF4 | FECD | CTG | -- | >50 | 88.01 | [117,118] | |
3′ UTR | DMPK | DM1 | CTG | 5 to 37 | >50 | 14.63 | [119,120] | |
3′ UTR | ATXN8OS | SCA8 e | CTG | 6 to 37 | >74 | 68.00 f | [121,122,123] | |
Exon | ATXN8 | SCA8 e | CAG | 15 to 50 | 71 to 1300 | 100.00 f | [124] | |
Promoter | CSTB | EPM1 | CCCCGCCCCGCG | 2 to 3 | >14 | 40.82 | [125,126] |
Gene | Repeat Sequence | Sense Translation | Antisense Translation |
---|---|---|---|
FXS | CGG-CGG-CGG-CGG | R-R-R-R | A-A-A-A |
GGC-GGC-GGC-GGC | G-G-G-G | P-P-P-P | |
GCG-GCG-GCG-GCG | A-A-A-A | R-R-R-R | |
DIP2B | CGG-CGG-CGG-CGG | R-R-R-R | A-A-A-A |
GGC-GGC-GGC-GGC | G-G-G-G | P-P-P-P | |
GCG-GCG-GCG-GCG | A-A-A-A | R-R-R-R | |
FMR2 | GCC-GCC-GCC-GCC | A-A-A-A | R-R-R-R |
CCG-CCG-CCG-CCG | P-P-P-P | G-G-G-G | |
CGC-CGC-CGC-CGC | R-R-R-R | A-A-A-A | |
C9orf72 | GGG-GCC-GGG-GCC | G-A-G-A | P-R-P-R |
GGG-CCG-GGG-CCG | G-P-G-P | P-G-P-G | |
GGC-CGG-GGC-CGG | G-R-G-R | P-A-P-A | |
FXN | GAA-GAA-GAA-GAA | E-E-E-E | L-L-L-L |
AAG-AAG-AAG-AAG | K-K-K-K | F-F-F-F | |
AGA-AGA-AGA-AGA | R-R-R-R | S-S-S-S | |
CNBP | CCT-GCC-TGC-CTG | P-A-C-L | G-R-T-G-G |
CTG-CCT-GCC-TGC | L-P-A-C | G-G-R-T-G | |
TGC-CTG-CCT-GCC | C-L-P-A | T-G-G-G-R | |
ATXN10 | ATT-CTA-TTC-TAT-TCT | I-L-F-F-T | STOP-D-K-I-R |
TTC-TAT-TCT-ATT-CTA | F-F-S-I-L | K-I-R-STOP-D | |
TCT-ATT-CTA-TTC-TAT | S-I-L-F-F | R-STOP-D-K-I | |
TCF4 | CTG-CTG-CTG-CTG | L-L-L-L | D-D-D-D |
TGC-TGC-TGC-TGC | C-C-C-C | P-P-P-P | |
GCT-GCT-GCT-GCT | A-A-A-A | R-R-R-R | |
DMPK | CTG-CTG-CTG-CTG | L-L-L-L | D-D-D-D |
TGC-TGC-TGC-TGC | C-C-C-C | P-P-P-P | |
GCT-GCT-GCT-GCT | A-A-A-A | R-R-R-R | |
JPH3 | CTG-CTG-CTG-CTG | L-L-L-L | D-D-D-D |
TGC-TGC-TGC-TGC | C-C-C-C | P-P-P-P | |
GCT-GCT-GCT-GCT | A-A-A-A | R-R-R-R | |
ATXN8 | CTG-CTG-CTG-CTG | L-L-L-L | D-D-D-D |
TGC-TGC-TGC-TGC | C-C-C-C | P-P-P-P | |
GCT-GCT-GCT-GCT | A-A-A-A | R-R-R-R | |
CSTB | CCC-CGC-CCC-GCG | P-R-P-A | G-A-G-R |
CCC-GCC-CCG-CGC | P-A-P-R | G-R-G-A | |
CCG-CCC-CGC-GCC | P-P-R-A | G-G-A-R |
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Darling, A.L.; Uversky, V.N. Intrinsic Disorder in Proteins with Pathogenic Repeat Expansions. Molecules 2017, 22, 2027. https://doi.org/10.3390/molecules22122027
Darling AL, Uversky VN. Intrinsic Disorder in Proteins with Pathogenic Repeat Expansions. Molecules. 2017; 22(12):2027. https://doi.org/10.3390/molecules22122027
Chicago/Turabian StyleDarling, April L., and Vladimir N. Uversky. 2017. "Intrinsic Disorder in Proteins with Pathogenic Repeat Expansions" Molecules 22, no. 12: 2027. https://doi.org/10.3390/molecules22122027