Table 2.

Post-translational modifications of Keap1.

Modification	Residue	Increase in Nrf2 activity	Reference
Ubiquitination*	K39, K61, K84, K97, K108, K287, K312, K615	Yes (essential for Keap1 degradation)	[82,89]
S-nitrosation*	C151, C273	Yes	[9,84–86]
Alkylation (itaconate)	C151, C257, C273, C288, C297	Yes (modifies and lowers Keap1 level)	[90]
Carbonylation	C273, C288	Yes	[91]
Glycosylation	S104	No (crucial in mediating Nrf2 ubiquitination)	[92]
S-glutathionylation	C434	Yes	[93,94]
MICA (methylimidazole crosslink between proximal cysteine and arginine residues)	MICA crosslink between C151 and R135	Yes	[87]
Nitro fatty acids	C38, C226, C257. C273, C288, C489	Yes	[95]
Oxidation	disulphide between C226 and C613; intramolecular between C151	Yes	[25,26]
Phosphorylation	Y206, Y263, Y334,	Yes (enabling Keap1 nuclear export)	[96]
Succination	C151, C288	Yes	[97–99]
Sulfhydrylation	C151	Yes	[100]
Malonylation	K131	n.d.	[101]
Acetylation	K131	n.d.	[102]
Palmitoylation	n.d.	n.d.	[103]

^*- the modifications that are both mediated by Keap1 and exerted on Keap1 protein itself.