Table 2.

Post-translational modifications (PTM) of OATs

Type of PTM	OATs	Details	Ref.
Phosphorylation	mOat1	Treatment with phosphatase inhibitor okadaic acid promotes serine/threonine phosphorylation and inhibits mOat1 transport activity.	34
Glycosylation	mOat1 hOAT1 hOAT4	Treatment with N-linked glycosylation inhibitor, tunicamycin, or mutagenesis of all glycosylation sites impaires the targeting of OATs to the plasma membrane and inhibits OAT transport activity.	32,33,94
	hOAT4	Expression of OAT4 in cells defective in processing of oligosaccharides from mannose-rich type to complex type decreases the affinity of OAT4 for its substrates.	33
Ubiquitination	rOat1 hOAT1 hOAT3	Treatment of OAT-expressing cells or rat kidney slides with protein kinase C activator, PMA, increased OAT ubiquitination, while PKC inhibitor staurosporin blocked OAT ubiquitination.	8,42
	hOAT1 hOAT3 hOAT4	Overexpression of Nedd4-2 increased OAT ubiquitination and decreased OAT activity. siRNA knockdown of endogenous Nedd4-2 abolished PKC-stimulated OAT1/OAT3 ubiquitination, reversed PKC-induced decrease of OAT activity. Knockdown of endogenous Nedd4-2 also abolished sgk2-stimulated OAT4 activity.	7,8,74
	hOAT1	LC-MS/MS detected Lys48-linked polyubiquitin peptides conjugated to OAT. Ubiquitin mutant Ub-K48R prevents the formation of polyubiquitin chains, abolishes PKC-stimulated OAT1 ubiquitination, internalization and PKC-induced decrease in OAT expression at the cell expression.	42
		Mutagenesis of Lys297, Lys303 and Lys315 abolished PKC-stimulated OAT1 ubiquitination.	59
		Overexpression of Nedd4-1 increased OAT1 ubiquitination and decreased OAT transport activity.	7