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. 2021 Jul 5;8:693325. doi: 10.3389/fmolb.2021.693325

TABLE 1.

PTMs and their effects on RBP’s aggregation.

PTM RBP Residue Effects on Aggregation References
R-methylation FUS Arg 216, Arg 259 graphic file with name fmolb-08-693325-fx1.jpg Qamar et al. (2018)
Arg 407, Arg 472
Arg 473, Arg 476
Phosphorylation FUS Ser 26/Ser 30 graphic file with name fmolb-08-693325-fx2.jpg 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.) graphic file with name fmolb-08-693325-fx3.jpg Ryan et al. (2021)
TDP - 43 Ser 48 graphic file with name fmolb-08-693325-fx4.jpg Hornbeck et al. (2012), Hornbeck et al. (2015)
Rigbolt et al. (2011), Wang A. et al. (2018)
TDP - 43 Ser 403/404 graphic file with name fmolb-08-693325-fx5.jpg Neumann et al. (2020)
Ser 409/410
Acetylation FUS Lys 510 graphic file with name fmolb-08-693325-fx6.jpg Arenas et al. (2020)
FUS Lys 315/316 graphic file with name fmolb-08-693325-fx7.jpg Arenas et al. (2020)
FUS Ala 2 graphic file with name fmolb-08-693325-fx8.jpg Bock et al. (2021)
TDP - 43 Lys 145–149 graphic file with name fmolb-08-693325-fx9.jpg Cohen et al. (2015)
Ubiquitination TDP - 43 Lys 48, Lys 63 graphic file with name fmolb-08-693325-fx10.jpg Hebron et al. (2013)
TDP - 43 Lys 263 graphic file with name fmolb-08-693325-fx11.jpg Hans et al. (2014)
PARylation hnRNP - A1 Lys 298 graphic file with name fmolb-08-693325-fx12.jpg Duan et al. (2019)
FUS n.d graphic file with name fmolb-08-693325-fx13.jpg 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.