Table 1. Observed protein–protein interactions with RBR E3 ubiquitin ligases.
Detection methods: 2H, yeast or mammalian-two hybrid; AUbA, autoubiquitination assay; CE, co-elution during chromatography purification; FRET, FRET in vivo; IF, immunofluorescence; IP, immunoprecipitation; ITC, isothermal calorimetry; LCMS, liquid chromatographyMS/MS; NMR, nuclear magnetic resonance; PD, pulldown using GST, His or MBP tag; Phos, in vitro phosphorylation; SPR, surface plasmon resonance; UbA, ubiquitination assay; UbSu, ubiquitin suicide inhibitor; X-ray, X-ray crystallography.
| RBR E3 ligase | Interacting protein | Detection method(s) | RBR-interaction site | Reference(s) |
|---|---|---|---|---|
| Parkin | UbcH7 (UBE2L3) | IP, 2H, AUbA, UbA, SPR | RING1 | [24,25,29,46,47,51,60,78,80,82,91–94,127,132,137–144] |
| UbcH5c (UBE2D3)/Ubc7 (UBE2G1)/UbcH6 (UBE2E1) | IP, UbA | [93,140,144,145] | ||
| UbcH8 (UBE2L6)/UbcH13 (UBE2N) | IP, PD, UbA | Rcat | [24,26,47,61] | |
| Ubiquitin-conjugating enzyme Variant 1a (Uev1a) | PD | RING1 | [61] | |
| 14-3-3η | IP, PD, UbA | RING0 | [143] | |
| 20S proteasome subunit α4 (PSMA7/XAPC7, subunit α type7) | 2H, IP | BRcat–Rcat | [83] | |
| 26S proteasome non-ATPase reg. subunit4 (Rpn10/S5a) | UbA, PD, NMR | Ubl | [30,79–82] | |
| α-Synuclein-interacting protein (Synphylin-1, Sph1) | IP, UbA, PD | Rcat | [94,141,143,145,146] | |
| All 1-fused gene from chromosome 6 (Afadin/AF-6) | IP, PD | Rcat | [147] | |
| Aminoacyl tRNA synthase complex coactivator (p38/JTV-1/AIMP2) | IP, PD | Ubl, RING1 | [82,91,94,146,148–150] | |
| Apoptosis regulator Bcl-2 | IP, PD | [151] | ||
| Bcl-2-associated athanogene 5 (BAG5) | IP, PD, UbA | [152,153] | ||
| Calcium/calmodulin dependent serine kinase (CASK/Lin2) | IP, PD, UbA | Rcat | [92] | |
| Carboxy terminus of Hsp70-interacting protein (CHIP) | IP, PD | [63] | ||
| Casein kinase 1 (CK1) | IP, PD, Phos | Ser101, Ser378 | [95,98] | |
| Catenin β-1 (β-catenin) | PD | [154] | ||
| Chondroitin-polymerizing factor (ChPF/Klokin1) | IP, 2H | [155] | ||
| Cul | IP, PD | [132] | ||
| Cdk5 | IP, PD | Ser131 | [94,95] | |
| Cyclin E | IP, PD, UbA | [132,142,156] | ||
| DJ-1 peptidase | IP, PD, UbA | [47,145,157,158] | ||
| Dopamine transporter (DAT) | IP, PD | [64] | ||
| E3 SUMO-protein ligase RanBP2 | IP, 2H, UbA | [78] | ||
| Endophillin-A1 | PD, UbA, NMR | Ubl | [111] | |
| Eps15 | PD, UbA, NMR, ITC | Ubl | [30,31] | |
| F-box/WD repeat-containing protein 7 (FBX30/SEL-10) | IP, PD | ΔUbl | [132] | |
| Heat-shock 70 kDa protein (Hsp70/chaperone protein DnaK) | IP | ΔUbl | [63,82,127] | |
| HDAC6 | IP, PD | RING0, RING1, Rcat | [70,71] | |
| Leu-rich PPR motif-containing protein (LRPPRC, LRP130) | IP | [59] | ||
| Leu-rich repeat kinase 2 (LRRK2) | IP | Rcat | [90] | |
| LIM kinase-1 (LIMK1) | IP, UbA | BRcat–Rcat | [91] | |
| Machado–Joseph disease protein 1 (Ataxin-3) | IP, UbA, PD, NMR | Ubl, BRcat–Rcat | [110,127,139,140] | |
| Mitochondrial Rho GTPase (Miro) | IP | [159,160] | ||
| Mitofusin-1 & 2 (MFN1, MFN2) | IP, UbA | [49,51–57] | ||
| Mortalin (HSPA9, GRP75, PBP74) | IP | [161] | ||
| Neuronal DnaJ/Hsp40 chaperone HSJ1a (DNAJB2a) | IP | [162] | ||
| O-glycosylated α-synuclein (αSp22) | IP, UbA | [60–62] | ||
| Parkin-associated endothelin receptor (Pael-R) | IP, UbA | [46,63] | ||
| Parkin co-regulated gene protein (PACRG/Glup) | IP | [163] | ||
| Parkin-interacting substrate (PARIS/ZNF476) | IP, PD, UbA | RING1, Rcat | [144] | |
| Prolierating cell nuclear antigen (PCNA) | IP | RING1 | [68,69] | |
| Protein interacting with C kinase 1 (PICK1/PRKCA BP) | IP, PD, UbA | Rcat | [93] | |
| Protein kinase A (PKA) | Phos | Ser101, Ser131, Ser236, Ser378 | [98] | |
| Protein kinase C (PKC) | Phos | Ser296, Ser378 | [98] | |
| PINK1 | IP, UbA, Phos, PD, LCMS | Ser65, Thr175 | [49,99–102,145,164–168] | |
| RNF41/NRDP1/FLRF | IP, 2H, PD, UbA | Ubl | [150,169] | |
| Septin4 (ARTS/CDCrel-2)/Septin5 (CDCrel-1/PNUTL1) | IP, 2H, PD | RBR | [26,82,83,138,170] | |
| Small ubiquitin-related modifer-1 (SUMO-1) | IP, PD | [77] | ||
| Synaptotagmin XI (Syt11) | 2H, IP, UbA | RING1 | [171] | |
| TDP-43 | IP, PD | [71] | ||
| Transcription factor single-minded 2 (SIM2) | IP | BRcat–Rcat | [72] | |
| TOMM70A | IP, PD | [58,59] | ||
| Tubulin (α, β & γ) | IP, PD, CE | RING0, RING1, Rcat | [82,172–174] | |
| Tyrosine protein kinase ABL1 (c-Abl) | IP, PD | Tyr143 | [96,97] | |
| HHARI (Ariadne 1) | UbcH7 (UBE2L3) | IP, 2H, IF, CE, ITC, PD, UbA | RING1 | [27,29,37,42,114,175] |
| UbcH8 (UBE2L6) | IP | Rcat | [27] | |
| α-Synuclein | IF | [176] | ||
| α-Synuclein interacting protein (Synphilin-1, Sph1) | IF | [176] | ||
| Cul-1,2,3,4A (NEDD8-dependent) | IP, UbSu | Acidic/Gly | [37] | |
| Transcription factor single-minded (SIM2) | IP | [72] | ||
| Translation initiation factor 4F homologous protein (4EHP) | IP, 2H | RING1 | [76] | |
| TRIAD1 (Ariadne-2) | UbcH7 (UBE2L3) | IP, 2H, PD, PD, UbA | RING1 | [37,177–179] |
| UbcH6 (UBE2E1/UbcH8 (UBE2L6)/UbcH13 (UBE2N) | IP, 2H, PD | Rcat | [177–179] | |
| Cul-5 (NEDD8-dependent) | IP, UbA | [37] | ||
| Growth factor independence 1 & 1B (Gfi1, Gfi1B) | IP, 2H, PD | Rcat | [180] | |
| MDM2 | UbA | [84] | ||
| Nuclear Inhibitor of NF-κB β (IκBβ) | IP | [181] | ||
| p53 | IP, PD | [182,183] | ||
| Promyelocytic leukaemia-retinoic acid receptor α (PML-RARα) | IP, IF | [179] | ||
| Parc (CUL9) | UbcH7 (UBE2L3) | UbA | [131] | |
| Cul-7 | IP | [88,184] | ||
| NEDD8 | IP, LCMS | Cullin at Lys1881 | [88,89] | |
| p53 | IP, PD, IF, CE, NMR | CPH | [41,88,131,185] | |
| Ring box protein-1 (Rbx1) | IP | [88] | ||
| ARA54 (RNF14, HRIHFB2038, HFB30 and TRIAD2) | UbcH6 (UBE2E1)/UbcH8 (UBE2L6)/UbcH9 (UBE2E3) | 2H, AUbA | RING1 | [186] |
| Androgen receptor | IP, 2H, PD, SPR, FRET, X-ray | C-term FXXL(F/Y) | [73,74,187–194] | |
| Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) | 2H, M2H, PD | [195] | ||
| p300/CBP-associated factor | 2H | [188] | ||
| T-cell factors 1 & 4 (TCF1, TCF4) | IP, PD | [196] | ||
| TRIAD3 (RNF216, ZIN) | UbcH7 (UBE2L3)/UbcH8 (UBE2L6) | IP | [197] | |
| Killer cell Ig-like receptor (KIR) 2DL4 | IP, 2H | RBR | [198] | |
| Receptor interacting serine/threonine-protein kinase-1 (RIP1) | IP | [103] | ||
| TNF receptor-associated factor 3 (TRAF3) | IP | N-term PXQX(T/S) | [199] | |
| Toll/interleukin-1 receptor adaptor protein (TIRAP) | IP | [103] | ||
| Toll-like receptors 3,4,5, and 9 (TLR3,4,5,9) | 2H | [197] | ||
| Virion infectivity factor (Vif) of HIV-1 | IP, PD | [200] | ||
| HOIP (PAUL, RNF31) | HOIL-1 | IP, PD, CE, UbA, SPR, X-ray, NMR | UBA (via HOIL-1 Ubl) | [32,38,43–45,134,201–203] |
| Sharpin (Sipl1) | IP, CE, UbA | NZF2 | [38,43,45,133,134,202–205] | |
| UbcH7 (UBE2L3) | UbA | RING1–BRcat | [38,44,45,201,206] | |
| UbcH5A (UBE2D1)/UbcH5B (UBE2D2)/UbcH5C (UBE2D3) | UbA | RING1–BRcat | [39,43–45,65,85,105,134,201] | |
| E2-25K (UBE2K) | UbA | [201] | ||
| NEMO | IP, PD, UbA | [39,65,67,133,134,205–207] | ||
| B-cell surface antigen CD40 (CD40) | IP | [207] | ||
| Muscle-Specific receptor tyrosine Kinase (MuSK) | 2H | [104] | ||
| Nucleotide-binding oligomerization domain protein 2 (NOD2) | IP | [208,209] | ||
| OTU domain deubiquitinase with linear link specificity (Gumby) | IP | [87] | ||
| Polyubiquitin chains (Lys63>linear>Lys48) | IP, PD, ITC | NZF1 | [38,66,210] | |
| Tumour necrosis factor receptor 1 signalling complex (TNF-RSC) | IP | [66,85,211] | ||
| HOIL-1 | cIAP1/2 | IP | [66] | |
| Nucleotide-binding oligomerization domain protein 2 (NOD2) | IP | [208,209] | ||
| Polyubiquitin chains (linear>Lys63) | PD, SPR, X-ray, ITC | Ubl, NZF | [38,39,66,210] | |
| Protein kinase C (PKC) | 2H, UbA | Ubl | [105] | |
| Retinoic acid-inducible gene 1 protein (RIG-1) | PD | NZF | [85] | |
| Suppressor of cytokine signalling 6 (SOCS-6) | IP, 2H | Ubl | [212] | |
| Tumour necrosis factor α-induced protein 3 (A20) | IP | [211] | ||
| Tumour receptor-associated factor 2 (TRAF2) | IP | [66] | ||
| RNF144A | UbcH7 (UBE2L3) | 2H | [213] | |
| RNF144B (p53RFP/IBRDC2/PIR2) | UbcH7 (UBE2L3)/UbcH8 (UBE2L6) | IP | RBR | [214] |
| Bcl-2 associated protein X (BAX) | IP | [215] | ||
| CDK-interacting protein 1 (p21WAF1) | IP | [216] | ||
| Leukaemic nucleophosmin protein (NPMc) | IP | [217] | ||
| p53, p63, p73 | IP | [216,218–220] | ||
| Dorfin (RNF19) | UbcH7 (UBE2L3)/UbcH8 (UBE2L6) | IP | RBR | [221] |
| α-Synuclein interacting protein (Synphillin-1, Sph1) | IP, UbA | [222] | ||
| Calcium-sensing receptor | IP, 2H | C-terminal extension | [223] | |
| Cu/Zn SOD1 (ALS mutants; G37R/H46R/G85R/G93A) | IP, UbA | C-terminal extension | [224–228] | |
| Ubiquitinated-substrates (not defined) | IP | RBR and C-terminal extension | [221] | |
| Valosin-containing protein (p97/Cdc48 homologue) | IP, IF, LCMS | [223,226] | ||
| Vimentin | IF | [221] |