Table 1.

Summary of SUMO substrates discussed in this review. The table summarizes the sites of modification and SUMO paralogues that target the proteins discussed. Where known, E3s and deSUMOylating enzymes that have activity against the target protein are indicated. Question marks (?) indicate instances where truncated or isolated catalytic domains of SENPs have been used to deSUMOylate the target protein, which may not reflect SENP substrate specificity in vivo

	SUMO site	SUMO paralogues	E3s	SENPs	Role of SUMOylation	References
Synaptic neurotransmitter receptors and transporters
mGluR7	K889	SUMO1/3	Binds PIAS1 and PIAS3L	SENP1	Enhances surface stability of mGluR7	Choi et al., (2016), Dutting et al., (2011), Tang et al., (2005)
mGluR8b	K882	SUMO1	PIAS1; Binds PIAS3L	Unknown	Unknown	Dutting et al., (2011), Tang et al., (2005)
M1 mAChR	K327	SUMO1	Unknown	Unknown	Promotes ligand‐binding affinity and signal transduction	Xu et al., (2019)
GluK2	K886	SUMO1	Binds PIAS3	SENP1?	Promotes agonist‐induced KAR internalization	Martin et al., (2007)
DAT	Unknown	SUMO1	Unknown	Unknown	Promotes DAT stability and surface expression	Cartier et al., (2019)
Ion channels and associated proteins
K2P1	K274	SUMO1	Unknown	SENP1	SUMOylation silences the channel	Rajan et al., (2005)
Kv1.5	K221, K536	SUMO1−3	Unknown	SENP2?	Alters the voltage dependence of steady‐state inactivation	Benson et al., (2007)
Kv2.1	K470	SUMO1	Unknown	SENP1	Inhibits channel currents by promoting desensitization; positive‐shifts the half maximal activation voltage	Dai, Kolic, Marchi, Sipione, and Macdonald, (2009), Plant et al., (2011)
Kv4.2	K437, K579	SUMO2/3	Unknown	Unknown	Increased surface expression and decreased maximal conductance	Welch et al., (2019)
Kv7.1	K424	SUMO1/2	Unknown	SENP2	Causes a positive shift in the half maximal activation voltage	Xiong et al., (2017)
Kv7.2	Unknown	SUMO1−3	Unknown	SENP2	Reduces channel currents	Qi et al., (2014)
Kv11.1	K21, K93, K116	SUMO1/2	Unknown	Unknown	Reduces channel currents	Steffensen et al., (2018)
Nav1.2	K38	SUMO1	Unknown	SENP1?	Increases channel currents	Plant et al. (2016)
TRPV1	K822	SUMO1	Unknown	SENP1	Enhances channel sensitivity to activation by heat	Wang et al., (2018)
CRMP2	K374	SUMO1−3	Unknown	SENP1, SENP2	Decreases calcium flux by Cav2.2 channels; Promotes Nav1.7 surface expression	Dustrude et al., 2013; Ju et al., (2013)
Synaptic and synapse‐associated proteins
Synapsin 1a	K687	SUMO1	Unknown	SENP1?	Promotes binding to synaptic vesicles (SVs), required for normal levels of SV exocytosis	Tang et al., (2015)
FMRP	K88, 130, 614	SUMO1	Unknown	Unknown	Promotes dissociation of FMRP from RNA granules to promote spine formation	Khayachi et al., (2018)
Arc	K110, K268	SUMO1−3	Unknown	SENP1?	Required for homeostatic upscaling; Promotes interaction with drebrin A during LTP	Craig et al., (2012), Nair et al., (2017)
α‐synuclein	Predominantly K96, K109	SUMO1−3	PIAS2, PC2, TRIM28	Unknown	Effects reported on synuclein localization, stability, aggregation and toxicity	Dorval and Fraser, (2006); Oh et al., (2011); Rousseaux et al. (2018); Rott et al., (2017)
NOS	K725, K739	SUMO1	PIAS3	Unknown	Required for LTP induction and expression of Arc and BDNF	Du et al., (2020)
Small GTPases
Rac1	K183, K184, K186, K188	SUMO1	PIAS3	SENP1 and 3 proposed	Promotes Rac1 activity and downstream signalling	Castillo‐Lluva et al., (2010), Yang et al., (2019)
Ras	K42	Predominantly SUMO3	PIASγ	SENP1, SENP2	Required for full activation of downstream signalling pathways	Choi, Chen, et al. (2018))
Rab17	K68	SUMO1−3	Unknown	SENP1?	Promotes interaction with Syntaxin−2 and reduces apical vesicle docking	Striz and Tuma, (2016)
Control of local translation
CPEB3	Unknown	SUMO2/3	Unknown	Unknown	Fusion of SUMO2 to CPEB3 prevents CPEB3 aggregation, repressing local translation	Drisaldi et al., (2015)
Others
mHTT	K6, K9, K15, K91	SUMO1, SUMO2	Rhes, PIAS1	Unknown	Promotes mHTT toxicity by enhancing its solubility	O'Rourke et al., (2013), Steffan et al., (2004), Subramaniam et al., (2009)