6kcz

Structural highlights

Function

[UBP20_HUMAN] Deubiquitinating enzyme involved in beta-2 adrenergic receptor (ADRB2) recycling. Acts as a regulator of G-protein coupled receptor (GPCR) signaling by mediating the deubiquitination beta-2 adrenergic receptor (ADRB2). Plays a central role in ADRB2 recycling and resensitization after prolonged agonist stimulation by constitutively binding ADRB2, mediating deubiquitination of ADRB2 and inhibiting lysosomal trafficking of ADRB2. Upon dissociation, it is probably transferred to the translocated beta-arrestins, possibly leading to beta-arrestins deubiquitination and disengagement from ADRB2. This suggests the existence of a dynamic exchange between the ADRB2 and beta-arrestins. Deubiquitinates DIO2, thereby regulating thyroid hormone regulation. Deubiquitinates HIF1A, leading to stabilize HIF1A and enhance HIF1A-mediated activity. Mediates deubiquitination of both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.^{[1] [2] [3] [4]}

References

1. ↑ Li Z, Wang D, Na X, Schoen SR, Messing EM, Wu G. Identification of a deubiquitinating enzyme subfamily as substrates of the von Hippel-Lindau tumor suppressor. Biochem Biophys Res Commun. 2002 Jun 14;294(3):700-9. PMID:12056827 doi:http://dx.doi.org/10.1016/S0006-291X(02)00534-X
2. ↑ Curcio-Morelli C, Zavacki AM, Christofollete M, Gereben B, de Freitas BC, Harney JW, Li Z, Wu G, Bianco AC. Deubiquitination of type 2 iodothyronine deiodinase by von Hippel-Lindau protein-interacting deubiquitinating enzymes regulates thyroid hormone activation. J Clin Invest. 2003 Jul;112(2):189-96. doi: 10.1172/JCI18348. PMID:12865408 doi:http://dx.doi.org/10.1172/JCI18348
3. ↑ Li Z, Wang D, Messing EM, Wu G. VHL protein-interacting deubiquitinating enzyme 2 deubiquitinates and stabilizes HIF-1alpha. EMBO Rep. 2005 Apr;6(4):373-8. doi: 10.1038/sj.embor.7400377. PMID:15776016 doi:http://dx.doi.org/10.1038/sj.embor.7400377
4. ↑ Berthouze M, Venkataramanan V, Li Y, Shenoy SK. The deubiquitinases USP33 and USP20 coordinate beta2 adrenergic receptor recycling and resensitization. EMBO J. 2009 Jun 17;28(12):1684-96. doi: 10.1038/emboj.2009.128. Epub 2009 May 7. PMID:19424180 doi:http://dx.doi.org/10.1038/emboj.2009.128