Table 2.
Proposed human ubiquitin readers with cell cycle functions
UBDUbiquitin binding modeNumber of UBD-containing proteins (cell cycle associated/total)Examples with cell cycle functionsUbiquitin-binding role in cell cycle functionaReference
UBA MonoUb, polyUb (predominant for K48) 14/55 UBQLN2,b KPC2,b,c FAF1,d UBASH3B,c BRSK1/2, LATS1/2, MARK4 KPC2 (E3 ligase subunit): Promotes the transfer of ubiquitylated p27 to the proteasome; UBASH3B: Targets ubiquitylated Aurora B to microtubules in mitosis Hara et al., 2005; Krupina et al., 2016  
CUE MonoUb 1/13 CUEDC2c CUEDC2: Promotes MCC release from APC/CCDC20 Gao et al., 2011  
UIM MonoUb, polyUb (K48, K63) 6/28 DDI1,b RPN10,b Epsin-1, MAT1, alpha4c alpha4: Prevents polyubiquitylation of the PP2A catalytic subunit Kong et al., 2009; McConnell et al., 2010  
UBP PolyUb 1/3 USP39 None described — 
NZF MonoUb, polyUb (K63) 2/7 NPL4,d HOIL-1 None described — 
UEV MonoUb 1/2 TSG101 None described — 
UBAN DimonoUb (M1) 2/7 ALIX, Optineurin None described — 
WD40 (subset) MonoUb 1/4 BUB3 None described — 
Unique or uncharacterized domains Various 10/21 RPN13,b VCP,d UFD1,d NUP62, ERα, SMURF2c SMURF2 (E3 ligase): Stabilize ubiquitylated substrate binding to promote polyUbe Ogunjimi et al., 2010  
Domains not found in cell cycle regulators Various 0/22 — — — 
Total — 38/162 — — — 
UBDUbiquitin binding modeNumber of UBD-containing proteins (cell cycle associated/total)Examples with cell cycle functionsUbiquitin-binding role in cell cycle functionaReference
UBA MonoUb, polyUb (predominant for K48) 14/55 UBQLN2,b KPC2,b,c FAF1,d UBASH3B,c BRSK1/2, LATS1/2, MARK4 KPC2 (E3 ligase subunit): Promotes the transfer of ubiquitylated p27 to the proteasome; UBASH3B: Targets ubiquitylated Aurora B to microtubules in mitosis Hara et al., 2005; Krupina et al., 2016  
CUE MonoUb 1/13 CUEDC2c CUEDC2: Promotes MCC release from APC/CCDC20 Gao et al., 2011  
UIM MonoUb, polyUb (K48, K63) 6/28 DDI1,b RPN10,b Epsin-1, MAT1, alpha4c alpha4: Prevents polyubiquitylation of the PP2A catalytic subunit Kong et al., 2009; McConnell et al., 2010  
UBP PolyUb 1/3 USP39 None described — 
NZF MonoUb, polyUb (K63) 2/7 NPL4,d HOIL-1 None described — 
UEV MonoUb 1/2 TSG101 None described — 
UBAN DimonoUb (M1) 2/7 ALIX, Optineurin None described — 
WD40 (subset) MonoUb 1/4 BUB3 None described — 
Unique or uncharacterized domains Various 10/21 RPN13,b VCP,d UFD1,d NUP62, ERα, SMURF2c SMURF2 (E3 ligase): Stabilize ubiquitylated substrate binding to promote polyUbe Ogunjimi et al., 2010  
Domains not found in cell cycle regulators Various 0/22 — — — 
Total — 38/162 — — — 

We considered UBD-containing proteins annotated in UniProtKB/Swiss-Prot, a curated protein database (UniProt Consortium, 2015), together with a manual literature search. Our criteria include (1) proteins containing UBDs described previously (Husnjak and Dikic, 2012), (2) other proteins annotated as binding ubiquitin, and (3) manual exclusion in case of covalent ubiquitin binding (e.g., E2s or ubiquitin modification) and of active DUBs. Assignment of cell cycle–related functions was determined by gene ontology and complemented with manual literature search. Ubiquitin-binding mode is according to Husnjak and Dikic (2012). MonoUb, monoubiquitylation; polyUb, polyubiquitylation; —, not applicable.

a

Excluding proteins involved in general proteasome function or that of VCP/p97.

b

Proteasome subunit, or proteasome associated (mostly according to Grice and Nathan, 2016).

c

Proteins have a reported cell cycle function for their UBDs that is distinct from general proteasome or VCP/p97 functions.

d

VCP/p97 component or cofactor (Meyer et al., 2012).

e

Probably a general mechanism, which includes its cell cycle functions.

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