Table 2.

Ub-binding endocytic regulators and their functions

Protein		UBD	Protein function
Yeast	Mammals
Ede1p	Eps15	UBA/UIM	Endocytic adaptor protein at the plasma membrane and sorting endosome. Endocytosis of ubiquitylated EGFRs and endosomal sorting in mammalian cells
Ent1p/2p	Epsin1/2	UIM	Endocytic adaptor protein at the plasma membrane. Internalization of Ste2p in yeast and endocytosis of ubiquitylated EGFRs in mammalian cells
Gga	GGA	GAT	Monomeric clathrin adaptor protein. Ub-dependent sorting of Gap1 from the TGN to endosomes and EGFRs from early endosomes to the lysosome
Hse1p	STAM1/2	UIM and VHS	Endocytic adaptor protein at the sorting endosome. Sorting of vacuolar markers into the vacuole in yeast and of ubiquitylated cargo, including EGFRs, into the MVB in mammalian cells
—	TOM1	GAT	Adaptor protein with VHS and GAT domains recruited to early endosomes by Tollip. Recruitment of ubiquitylated proteins to early endosomes
Vps9p	Rabex-5	CUE/?	GEF for Vps21p/Rab5 at the sorting endosome. Sorting of Ste2p into the vacuole in yeast
Vps23p	TSG101	UEV	ESCRT-I component. Sorting of monoubiquitylated CPS into the MVB in yeast and of ubiquitylated EGFRs for lysosomal degradation in mammalian cells
Vps27p	Hrs	UIM	Endocytic adaptor protein at the sorting endosome. Sorting of ubiquitylated cargo into the vacuole in yeast and of ubiquitylated EGFRs and TfR-Ub chimera into the MVB in mammalian cells
Vps36p	Eap45	NZF/GLUE	ESCRT-II component. Sorting of ubiquitylated cargo into the vacuole/MVB
The functions of endocytic Ub-binding proteins and the role of their UBDs in cellular processes are indicated. Some proteins have different UBDs in the yeast or mammalian homologs. In these cases, both domains are shown in the table with the yeast domain first and the mammalian second (i.e. UBA (yeast)/UIM (mammalian)). In the case of STAM1, both the UÌM and the VHS domain have been implicated in Ub binding. A UBD of Rabex-5 has not yet been published. CUE=coupling of Ub conjugation enzyme-like; EGFR=epidermal growth factor receptor; Eps15=epidermal growth factor receptor substrate 15; Epsin=Eps15-interacting protein; Gap1=general amino-acid permease; GAT=GGA and TOM1; GGA=Golgi-localized, gamma-ear-containing, Arf (ADP-ribosylation factor)-binding protein; GEF=guanine nucleotide exchange factor; GLUE=Gram-like Ub-binding in Eap45; ESCRT=endosomal sorting complex required for transport; Hrs=hepatocyte growth factor-regulated tyrosine kinase substrate; MVB=multivesicular body; NZF=Np14 zinc-finger; RIP=TNF receptor-interacting protein; STAM=signal-transducing adaptor molecule; TfR=transferrin receptor; TGN=trans-Golgi network; TOM1=target of Myb1; Ub=ubiquitin; TSG101=tumor susceptibility gene 101; UBA=Ub associated; UBD=Ub-binding domain; UEV=Ub E2 variant; UIM=Ub-interacting motif; VHS=Vps27, Hrs, STAM; Vps=vacuolar protein sorting.