Table 1.

List of UbK63 chain targets along different trafficking pathways.

Plasma Membrane
Organism	Target	E2/E3	DUB	Ub Receptor/Adaptor	References
Yeast	Uracil permease Fur4	NI 1/Rsp5	NI	NI	[13,31]
	General amino acid permease Gap1	NI/Rsp5	NI	NI	[25,29]
	Ferrichrome C transporter Arn1	NI/Rsp5	NI	NI	[30]
	Ferrioxamine B transporter Sit1	NI/Rsp5	NI	NI	[14]
	Lactate transporter Jen1	NI/Rsp5	NI	NI	[16]
Mammals	NGF receptor TrkA	UbcH7/TRAF6	CYLD	NI/p62	[32,33]
	MHC class I molecule	UbcH5, Ubc13/K3, K5	NI	Epsin 1, Eps15	[34,35,36]
	Dopamine transporter DAT	UBE2D, UBE2L3/Nedd4-2	NI	Epsin 1, Esp15, Eps15R	[37,38]
	Aquaporin-2 water channel	NI/Nedd4, Cul5	NI	NI	[39]
	Prolactin receptor	NI/SCFβ-TRCP	NI	NI	[40]
	human κ-opioid receptor	NI	NI	NI	[41]
	LDL receptor	UBE2D/IDOL	NI	NI	[42,43]
	EGF receptor	NI/c-Cbl	NI	Epsin 1, Ankrd 13	[44,45,46]
	Interferon receptor IFNAR1	SCFβ-TRCP	BRCC36 (BRISC-SHMT2 complex)	NI	[47,48,49]
	α-subunit of Kv11.1 channel hERG-K	NI/CHIP	NI	NI	[50]
	IGF-I Receptor (IGF-IR)	NI/Mdm2	NI	NI	[51]
	TNF Receptor 1 (TNF-R1)	Ubc13/RNF8	NI	NI	[52]
	Cationic amino acid transporter (CAT-1)	NI/Nedd4-1, Nedd4-2	NI	NI	[53]
Plants	Auxin carrier PIN2	NI/ RGLG1, RGLG2	NI	TOL proteins	[54,55,56]
Golgi-Endosomes-MVBs
Organism	Target	E2/E3	DUB	Ub Receptor/Adaptor	References
Yeast	Rsp5 adapter Sna3	NI/Rsp5	NI	ESCRT 2	[57]
	Ferrioxamine B transporter Sit1	NI/Rsp5	NI	,,	[14]
	General amino acid transporter Gap1	NI/Rsp5	NI	,,	[15]
	Carboxypeptidase S Cps1	NI/Rsp5	NI	,,	[15]
	Lactate transporter Jen1	NI/Rsp5	NI	,,	[16]
	Rsp5 adapter Ear1	NI/Rsp5	NI	,,	[58,59]
	Uracil permease Fur4	NI/Rsp5	NI	,,	[60,61]
Mammals	Melanocytic protein MART1	NI/Nedd4, Itch	NI		[58,62]
	EGF receptor	NI/NI NI/NI Ubc13/RNF126, Rabring 7 NI/Triad	NI AMSH NI	,,	[63] [64] [65] [66]
	GH Receptor (GHR)	NI/Triad	NI	,,	[66]
	E3 ligase c-Cbl	NI/NI	NI	NI	[63]
	E3 ligase Nedd4-L	NI/NI	NI	NI	[63]
	Solute carrier SLC3A2	NI/NI	NI	NI	[63]
	GTPase H-Ras	NI/Rabex-5	NI	NI	[67,68]
	Actin polymerization regulator WASH	Ube20/MAGE-L2-TRIM27	NI	NI	[69]
	Amyloid Precursor Protein (APP)	NI/NI	NI	NI	[70]
	α-synuclein (wild-type)	NI/Nedd4-1	NI	NI	[71]
Drosophila	GTPase H-Ras	NI/Rabex-5	NI	NI	[67]
Worms	Caveolin homolog Cav1	Ubc13/NI	NI	NI	[72]
Viral budding
Organism	Target	E2/E3	DUB	Ub receptor	References
HIV	Gag	NI/NEDD4-2s	NI	ALIX	[73,74]
Cytoskeleton
Organism	Target	E2/E3	DUB	Ub receptor	References
Mammals	Focal adhesion protein paxillin	Ubc13/RNF5	NI	NI	[75]
Mitochondria
Organism	Target	E2/E3	DUB	Ub receptor	References
Mammals	Mitofusin Mfn2	UbcH5/MITOL	NI	NI	[76]
	E3 ligase Parkin	NI/NI	NI	NI	[77]
	Ser/Thr kinase PINK1	NI/TRAF6-SARM1	NI	NI	[78]
Autophagy
Organism	Target	E2/E3	DUB	Ub receptor	References
Mammals	α-synuclein mutant isoforms pPhosphorylated α-synuclein	NI/Parkin NI/Parkin	NI NI	NI NI	[79] [80]
	DJ-1 mutant isoform (L166P)	Ubc13/Parkin	NI	HDAC6	[81]
	Synphilin-1	NI/Parkin	NI	NI	[82]
	sodium dismutase (SOD1) mutant isoform (G93A)	NI/ΝΙ	Ataxin-3	NI	[83]
	Caspase-8	NI/TRIM13	NI	NI	[84]

¹ Not Identified; ² For all reported examples, MVB sorting was shown to be dependent on UBD-containing ESCRT complexes.