TABLE 1.
PTM | RBP | Residue | Effects on Aggregation | References |
---|---|---|---|---|
R-methylation | FUS | Arg 216, Arg 259 | Qamar et al. (2018) | |
Arg 407, Arg 472 | ||||
Arg 473, Arg 476 | ||||
Phosphorylation | FUS | Ser 26/Ser 30 | Deng et al. (2014), Monahan et al. (2017) | |
Ser 30/Ser42 | Rhoads et al. (2018a) | |||
Thr 109/Ser 115 | ||||
Ser 115/Ser 117 | ||||
hnRNP - A2 | Tyr (n.d.) | Ryan et al. (2021) | ||
TDP - 43 | Ser 48 | Hornbeck et al. (2012), Hornbeck et al. (2015) | ||
Rigbolt et al. (2011), Wang A. et al. (2018) | ||||
TDP - 43 | Ser 403/404 | Neumann et al. (2020) | ||
Ser 409/410 | ||||
Acetylation | FUS | Lys 510 | Arenas et al. (2020) | |
FUS | Lys 315/316 | Arenas et al. (2020) | ||
FUS | Ala 2 | Bock et al. (2021) | ||
TDP - 43 | Lys 145–149 | Cohen et al. (2015) | ||
Ubiquitination | TDP - 43 | Lys 48, Lys 63 | Hebron et al. (2013) | |
TDP - 43 | Lys 263 | Hans et al. (2014) | ||
PARylation | hnRNP - A1 | Lys 298 | Duan et al. (2019) | |
FUS | n.d | Patel et al. (2015) |
PTMs are able to both suppress (red arrow down) and enhance (green arrow up) protein aggregation of FUS, TDP43 and hnRNP-A1/A2. R-methylation mainly suppresses FUS aggregation while ubiquitination and PARylation stimulates aggregation of TDP-43, hnRNP-A1 and FUS. Other PTMs such as phosphorlation and acetylation, have been shown to suppress or enhance aggregation propensity depending on the specific residue and protein modified.