Table 1.

E2s, E3s, and DUBs involved in the assembly or disassembly of branched ubiquitin chains

Branching E3s
Linkage typeMechanismE2s and E3sSubstratesFunctionTechnologyReferences
K11/K48 A APC/C + UBE2C +UBE2S Cyclin A Proteasomal degradation Ub mutation Meyer and Rape (2014)   
NEK2A Bispecific antibody Yau et al. (2017)   
Histone H2B Bispecific antibody Oh et al. (2020)   
B UBR5 + K11-specific E2/E3 73Q-HTT Proteasomal degradation Bispecific antibody Yau et al. (2017)   
K29/K48 B Ufd4 + Ufd2 Ub-V-GFP Proteasomal degradation Ub mutation Liu et al. (2017)   
B CRL2VHL or CRL4CRBN + TRIP12 BRD4 Targeted protein degradation Mass spectrometry, Ub-Clipping Kaiho-Soma et al. (2021)   
C HECTD1 N/A N/A UbiCRest, Mass spectrometry Harris et al. (2021)   
C UBE3C N/A
VPS34 		N/A
Proteasomal degradation 		Ub mutation, Mass spectrometry Wang et al. (2006)   
Ub mutation Chen et al. (2021)   
K6/K48 C IpaH9.8 N/A N/A Mass spectrometry Valkevich et al. (2014)   
C Parkin N/A Mitophagy Ub-clipping Swatek et al. (2019)   
C NlEL N/A N/A UbiCRest Hospenthal et al. (2013)   
N/A N/A Mass spectrometry Valkevich et al. (2014)   
K48/K63 B ITCH + UBR5 TXNIP Proteasomal degradation Ub mutation, Mass spectrometry Ohtake et al. (2018)   
B TRAF6 + HUWE1 TRAF6 NFkB signal activation Mass spectrometry, Ub mutation Ohtake et al. (2016)   
A? Ubc1/UBE2K N/A N/A Ub mutation Pluska et al. (2021)   
K11/K48/K63 C WWP1 WBP2 N/A Ub mutation French et al. (2017)   
A cIAP1 + UBE2D + UBE2N/UBE2V cIAP1, ER-α Targeted protein degradation Mass spectrometry, UbiCRest Akizuki et al. (2023)   
K63/M1 B TRAF6 + LUBAC IRAK1 NFkB signal activation UbiCRest Emmerich et al. (2013)   
RIP1 and RIP2 NFkB signal activation UbiCRest Emmerich et al. (2016)   
Multiple types B UBE2D + multiple RING E3s Luciferase, troponin I Inhibition of proteasomal degradation Ub mutation Kim et al. (2007)   
DUBs
Target branched linkageEffect of branched chainsDUBFamilyLinkage specificitySubstrateFunctionReferences
K29/K48 Retain TRABID/ZRANB1 OTU K29,K33>>K63 HECTD1 Protect from degradation Harris et al. (2021)  
K11/K48, K11/K63, M1/Oxyester Cezanne OTU K11, Oxyester APC/C substrates Protect from degradation Mevissen et al. (2016)  
M1/Oxyester N/A Inhibit NF-kB signal Rodriguez Carvajal et al. (2021)  
K6/K48 UPS30 USP K6 Parkin Inhibit mitophagy Deol et al. (2020b)  
K63/M1 Inhibition A20 OTU K63 RIPK-1 Inhibit NF-kB signal Wertz et al. (2015)  
K63/K48 CYLD USP K63, M1 TRAF6 Inhibit NF-kB signal Ohtake et al. (2016)  
K6/K48, K48/K63 Promotion UCH37 UCH K48 N/A Promote proteasomal degradation Deol et al. (2020b)  
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