Table.
Role of Ubiquitin in GPCR Downregulation
| Receptor | Abbr. | Ubiquitinated? | Ligase | DUB | ESCRT | Other Proteins Implicated in Regulating Lysosomal Trafficking |
Comments | Refs. |
|---|---|---|---|---|---|---|---|---|
| β1-adrenergic Receptor |
β1AR | NO | N/A | N/A | N/D | Resistant to downregulation |
50 | |
| β2-adrenergic Receptor |
β2AR | YES | Nedd4-1 | USP33 USP20 |
N/D | SNX27 Arrestins ARRDC3 |
Downregulates very slowly |
31, 55, 75, 84, 119 |
| Calcitonin Receptor-like Receptor |
CLR | NO | N/A | N/A | YES | RAMP1 ECE |
Still undergoes lysosomal downregulation |
61, 93 ,97 |
| Cannabinoid Receptor 1 |
CB1 | N/D | N/D | N/D | N/D | GASP1 | 105 | |
| Chemokine Receptor 4 |
CXCR4 | YES | AIP4 | N/D | YES | Arrestins |
48, 68, 78, 79, 80 |
|
| δ-opioid Receptor | DOR | YES | AIP4 | AMSH UBPY |
YES | GASP Dysbindin |
Ubiquitination not required for downregulation |
33, 71, 98, 99, 111 |
| Dopamine Receptor 2 |
D2R | N/D | N/D | N/D | N/D | GASP1 Dysbindin |
103, 111 | |
| κ-opioid Receptor | KOR | YES | N/D | CYLD | N/D | Lys63 specific polyubiquitin |
70 | |
| Neurokinin Receptor 1 |
NK1 | YES | N/D | N/D | N/D | ECE | 34, 92 | |
| Platelet Activating Factor |
PAF | N/D | c-Cbl | N/D | N/D | 77 | ||
| Proteolytically Activated Receptor 1 |
PAR1 | De-ubiquitinated | N/A | N/D | NO | SNX1 | 94, 95 | |
| Proteolytically Activated Receptor 2 |
PAR2 | YES | c-Cbl | AMSH UBPY |
YES | 49, 61 | ||
| Vasopressin Receptor 2 |
V2R | YES | N/D | N/D | N/D | Arrestins | Ubiquitinated at single residue |
69 |
N/A – Not Applicable, N/D – Not Determined