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Regulation of Receptors and Transporters by Ubiquitination: New Insights into Surprisingly Similar Mechanisms
Table 1.
Mammalian Plasma Membrane Transport Proteins that Undergo Ubiquitination
| Type of transport protein | Physiological function | Type of ubiquitinationa | E3 ligase | References |
|---|---|---|---|---|
| aThe type of ubiquitination is proposed based on indirect methods in most cases; bThis protein was previously classified as a channel but currently is re-classified as an antiporter. ND, not determined; WWP2; WW domain-containing protein 2. | ||||
| Transporter | ||||
| Sodium-dependent bile acid transporter (ASBT) | Bile acid absorption | Polyubiquitination | ND | (80) |
| Amino acid transporter (ATA2) | Sodium dependent transporter for neutral amino acids | Polyubiquitination | Nedd4-2 | (81) |
| Chloride/proton antiporter (ClC-5)b | Resorption of low molecular weight proteins in kidney | Polyubiquitination | Nedd4-2/WWP2 | (82) |
| Dopamine transporter (DAT) | Dopamine uptake-termination of neuro-transmission | Lys63-linked poly-ubiquitination | Nedd4-2 | (83) |
| Zinc transporter (ZIP4) | Regulation of intracellular zinc levels | Polyubiquitination | ND | (84) |
| Plasma membrane ATPases | ||||
| Sodium-Potassium ATPase (Na+-K+–ATPase) | Couple the hydrolysis of ATP to the transport of Na+ and K+ ions | α subunit Polyubiquitination | ND | (85) |
| P-Glycoprotein (P-gp) | ATP dependent drug transporter that extrude a variety of cytotoxic drugs | ND | ND | (86) |
| Channels | ||||
| Aquaporin1 and 2 (AQP1, AQP2) | Control of osmotic stress and water transport across cell membranes | Lys63-linked Polyubiquitination | ND | (67, 87) |
| Chloride/proton antiporter (ClC-2) | Regulation of ion homeostasis | Polyubiquitination | ND | (88) |
| Amiloride-sensitive epithelial sodium channel (ENaC) | Control of salt and fluid homeostasis in the kidney and the colon | α and γ subunits Polyubiquitination | Nedd4-2 | (62, 89) |
| Glycine receptor (GlyR) | Glycine-gated Cl− channel, mediates postsynaptic inhibition in central nervous system | α1 subunit monoubiquitination | ND | (90) |
| Voltage-gated potassium channel (KCNQ2/3, KCNQ3/5) | Regulator of neuronal excitability | Polyubiquitination | Nedd4-2 | (91) |
| Voltage gated sodium channels-several family members (Navs) | Generation and propagation of action potentials in neurons | Polyubiquitination | Nedd4-2 | (92, 93) |
| N-methyl-d-aspartate-type glutamate receptor (NMDA) | Glutamate-gated Ca++ channel, play central role in neuronal developments and information storage in brain | NR1 subunit Polyubiquitination | ER degradation complex/F-box protein | (94) |
| Inwardly rectifying potassium channel (ROMK1) | Recycling of potassium across the apical membrane of cortical collecting duct | Monoubiquitination | ND | (95) |
