Crosstalk between protein post-translational modifications and phase separation

Liu, Yang; Feng, Wenjuan; Wang, Yunshan; Wu, Bin

doi:10.1186/s12964-023-01380-1

Cell Communication and Signaling

Table 1 PTMs of proteins regulate LLPS in the physiopathological process

From: Crosstalk between protein post-translational modifications and phase separation

PTM	Protein	PTM Site	Effects of PTM on LLPS (↓↑)	Disease	Physiopathological process	References
	FUS	Ser, Thr	↑↓	ALS, FTD	Disease	[31, 50,51,52]
	TDP-43	Ser, Thr	↓	ALS, FTD	Disease	[53,54,55]
	Tau	Ser, Thr	↑↓	Alzheimer’s disease	Disease	[39, 56]
	hnRNPA2	Tyr	↓	ALS, FTD	Disease	[57]
	BRD4		↓	Cancer, AML, etc.	Disease	[21]
	BYSMV P	Tyr	↓		Viral infection	[58]
	SARS-CoV-2 N-proteins	Ser	↑↓	SARS-CoV-2	Viral infection	[59, 60]
	Phosphoprotein	Ser	↑	Measles	Viral infection	[61]
	TAZ		↓		Signal transduction	[62]
	P53	Ser	↓		Genetic transcription	[63]
	NBDY	Thr	↓		Cell function homeostasis	[64]
Phosphorylation	CIRBP	Ser	↓			[65]
	Stargazin	Ser	↑↓			[66]
	PARCL		↓			[67]
	CPEB		↓			[68]
	SMN	Ser	↑	ALS, FTD	Disease	[69]
	HP1α	NTE	↑		Genetic regulation	[42, 70]
	PGL-1/-3	Ser	↑		Environmental stress	[71]
	Liprin-α3	Ser	↑		Genetic regulation	[72]
	FMRP	Ser	↑	Fragile X syndrome	Disease	[73]
	NS2		↑	BT	Viral infection	[74]
	P62	Ser	↑		Disease	[75]
	TIAR-2	Ser	↑		Environmental stress	[76]
	Ddx4	Arg	↓			[23, 77]
	FUS	Arg	↓	ALS, FTD	Disease	[78, 79]
Methylation	hnRNPA2	Arg	↓	ALS, FTD	Disease	[80]
	FMRP	Arg	↓	Fragile X syndrome	Disease	[73]
	LSM4	Arg	↑			[81]
	RAP55A	Arg	↓	Primary biliary cirrhosis	Disease	[82]
	Tau	Lys	↑↓	Alzheimer’s disease	Disease	[38, 83, 84]
	TDP-43	Lys	↑	ALS, FTD	Disease	[85]
Acetylation	DDX3X	Lys	↓	Cancer, Intellectual disability	Disease	[86]
	BRD4	Lys	↑	Cancer, AML, etc.	Genetic transcription;	[21, 87]
	IRF3 / IRF7	Lys	↓		Viral infection	[88]
	FUS	N-terminal	↓	ALS, FTD	Disease	[89]
	H1	Lys			Genetic regulation	[90]
Ubiquitination	Tau	Lys	↑	Alzheimer’s disease	Disease	[91]
	SQSTM1	Leu	↓			[92]
	TRIM		↑		Cell function homeostasis	[93]
SUMOylation	SOP-2	Lys	↑		Genetic transcription	[94]
	SLX4		↑	Fanconi anemia	DNA repair	[95]
	CBX4	Lys	↑	AIDS	Viral infection	[96]
Neddylation	PML/RARα		↓	APL	Disease	[97]
O-GlcNAcylation	GAP	Thr	↓		Signal transduction	[98]
PARylation	CycT1		↓		Genetic transcription	[99]

Arrows (↓): Inhibit LLPS; Arrows (↑): Promote LLPS

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ISSN: 1478-811X

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