UBE2L6 (UbcH8) is an interferon-inducible E2 conjugating enzyme of the UBC fold that serves as the major E2 for the ubiquitin-like modifier ISG15 and also functions as a ubiquitin E2. It accepts ISG15 from the ISG15-specific E1 UBA7 (UBE1L) as a thioester on its active-site cysteine (Cys86) and passes it to E3 ligases such as HERC5 and TRIM25, enabling ISGylation of many cytosolic and some nuclear proteins, including antiviral effectors (RIG-I, PKR, MxA) and PCNA, after type I interferon stimulation. Like its close paralog UBE2L3 (UbcH7), it is also charged with ubiquitin by UBA1 and pairs with HECT-type (E6AP) and RBR/RING-type ligases (e.g. RNF19A, RNF19B, RNF144B, RNF40, SIAH1, ARIH2) to ubiquitinate substrates such as p53 (with E6/E6AP), syntaxin 1 and FLT3-ITD, promoting their proteasomal degradation. UBE2L6 is itself a target of ISGylation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000209 protein polyubiquitination | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA from deep E2 node PTN002514495. UbcH8 supports HECT-mediated polyubiquitination (Rsp5p/WBP2 in vitro; E6AP substrates) and RING/RBR-dependent ubiquitination leading to degradation (syntaxin 1, FLT3-ITD). Reason: UBE2L6 is inside the E2 clade that PAINT annotated, and human data show it transfers ubiquitin for HECT-dependent polyubiquitination. Chain assembly with UbcH7-like E2s is performed by the cognate HECT/RBR E3, so UBE2L6 contributes the E2 step; the ubiquitin role is real but its distinctive, IFN-induced role is ISG15 conjugation. Supporting Evidence: PMID:15131269 Rsp5p catalyzed efficient polyubiquitination of WBP2 in the presence of E1 Ub and UbcH8 PMID:9153201 only the E6AP-interacting E2s could function in conjunction with E6AP in the ubiquitination of an E6 independent substrate of E6AP |
| GO:0004842 ubiquitin-protein transferase activity | TAS PMID:9153201 Physical interaction between specific E2 and Hect E3 enzymes... | MODIFY | Summary: TAS from the paper that cloned UbcH8 as an E6AP-interacting E2 (PMID:9153201). Reason: Correct but general: UBE2L6 is an E2 that accepts ubiquitin from E1 by transthiolation and passes it to E3s; the specific descendant GO:0061631 ubiquitin conjugating enzyme activity (already carried by IBA and EC mapping) is the right term. Proposed replacements: ubiquitin conjugating enzyme activity Supporting Evidence: PMID:9153201 only the E6AP-interacting E2s could function in conjunction with E6AP in the ubiquitination of an E6 independent substrate of E6AP |
| GO:0005515 protein binding | IPI PMID:10085091 Cloning and characterization of human prostate coactivator A... | MODIFY | Summary: IPI binding of UBE2L6 to RNF14/ARA54 (RBR E3) (PMID:10085091). UBE2L6 is an E2 that is recruited by HECT, RBR and some RING E3 ligases; this interaction is an E2-E3 pairing. Reason: Bare protein binding is uninformative. The partner is a ubiquitin ligase, and E2-E3 pairing is the functional basis of UBE2L6 activity (E3s such as E6AP, Staring, Dorfin, p53RFP and NKLAM recruit UbcH8 and use it for substrate ubiquitination), so the informative term is ubiquitin protein ligase binding. This does not assert that every high-throughput pair is functional in vivo. Proposed replacements: ubiquitin protein ligase binding |
| GO:0005515 protein binding | IPI PMID:12121982 Staring, a novel E3 ubiquitin-protein ligase that targets sy... | MODIFY | Summary: IPI binding of UBE2L6 to rat RNF40/Staring (RING E3) (PMID:12121982). UBE2L6 is an E2 that is recruited by HECT, RBR and some RING E3 ligases; this interaction is an E2-E3 pairing. Reason: Bare protein binding is uninformative. The partner is a ubiquitin ligase, and E2-E3 pairing is the functional basis of UBE2L6 activity (E3s such as E6AP, Staring, Dorfin, p53RFP and NKLAM recruit UbcH8 and use it for substrate ubiquitination), so the informative term is ubiquitin protein ligase binding. This does not assert that every high-throughput pair is functional in vivo. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:12121982 Staring binds and recruits the brain-enriched E2 ubiquitin-conjugating enzyme UbcH8 to syntaxin 1 and facilitates the ubiquitination and proteasome-dependent degradation of syntaxin 1. |
| GO:0005515 protein binding | IPI PMID:16427630 The p53-inducible E3 ubiquitin ligase p53RFP induces p53-dep... | MODIFY | Summary: IPI binding of UBE2L6 to RNF144B/p53RFP (RBR E3) (PMID:16427630). UBE2L6 is an E2 that is recruited by HECT, RBR and some RING E3 ligases; this interaction is an E2-E3 pairing. Reason: Bare protein binding is uninformative. The partner is a ubiquitin ligase, and E2-E3 pairing is the functional basis of UBE2L6 activity (E3s such as E6AP, Staring, Dorfin, p53RFP and NKLAM recruit UbcH8 and use it for substrate ubiquitination), so the informative term is ubiquitin protein ligase binding. This does not assert that every high-throughput pair is functional in vivo. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:16427630 p53RFP interacts with E2 ubiquitin-conjugating enzymes UbcH7 and UbcH8 but not with UbcH5, and this interaction is mediated through the RING-IBR-RING domain of p53RFP. |
| GO:0005515 protein binding | IPI PMID:16709802 NK lytic-associated molecule, involved in NK cytotoxic funct... | MODIFY | Summary: IPI binding of UBE2L6 to RNF19B/NKLAM (RBR E3) (PMID:16709802). UBE2L6 is an E2 that is recruited by HECT, RBR and some RING E3 ligases; this interaction is an E2-E3 pairing. Reason: Bare protein binding is uninformative. The partner is a ubiquitin ligase, and E2-E3 pairing is the functional basis of UBE2L6 activity (E3s such as E6AP, Staring, Dorfin, p53RFP and NKLAM recruit UbcH8 and use it for substrate ubiquitination), so the informative term is ubiquitin protein ligase binding. This does not assert that every high-throughput pair is functional in vivo. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:16709802 We demonstrated that both UbcH7 and UbcH8 bind to full-length NKLAM. |
| GO:0005515 protein binding | IPI PMID:19549727 Analysis of the human E2 ubiquitin conjugating enzyme protei... | MODIFY | Summary: IPI binding of UBE2L6 to ARIH2/TRIAD1 (RBR E3) (PMID:19549727). UBE2L6 is an E2 that is recruited by HECT, RBR and some RING E3 ligases; this interaction is an E2-E3 pairing. Reason: Bare protein binding is uninformative. The partner is a ubiquitin ligase, and E2-E3 pairing is the functional basis of UBE2L6 activity (E3s such as E6AP, Staring, Dorfin, p53RFP and NKLAM recruit UbcH8 and use it for substrate ubiquitination), so the informative term is ubiquitin protein ligase binding. This does not assert that every high-throughput pair is functional in vivo. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:19549727 yeast two-hybrid (Y2H) screens were combined with true homology modeling methods to generate a high-density map of human E2/E3-RING interactions |
| GO:0005515 protein binding | IPI PMID:19549727 Analysis of the human E2 ubiquitin conjugating enzyme protei... | MODIFY | Summary: IPI binding of UBE2L6 to LONRF1 (RING E3) (PMID:19549727). UBE2L6 is an E2 that is recruited by HECT, RBR and some RING E3 ligases; this interaction is an E2-E3 pairing. Reason: Bare protein binding is uninformative. The partner is a ubiquitin ligase, and E2-E3 pairing is the functional basis of UBE2L6 activity (E3s such as E6AP, Staring, Dorfin, p53RFP and NKLAM recruit UbcH8 and use it for substrate ubiquitination), so the informative term is ubiquitin protein ligase binding. This does not assert that every high-throughput pair is functional in vivo. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:19549727 yeast two-hybrid (Y2H) screens were combined with true homology modeling methods to generate a high-density map of human E2/E3-RING interactions |
| GO:0005515 protein binding | IPI PMID:19549727 Analysis of the human E2 ubiquitin conjugating enzyme protei... | MODIFY | Summary: IPI binding of UBE2L6 to RNF144B/p53RFP (RBR E3) (PMID:19549727). UBE2L6 is an E2 that is recruited by HECT, RBR and some RING E3 ligases; this interaction is an E2-E3 pairing. Reason: Bare protein binding is uninformative. The partner is a ubiquitin ligase, and E2-E3 pairing is the functional basis of UBE2L6 activity (E3s such as E6AP, Staring, Dorfin, p53RFP and NKLAM recruit UbcH8 and use it for substrate ubiquitination), so the informative term is ubiquitin protein ligase binding. This does not assert that every high-throughput pair is functional in vivo. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:19549727 yeast two-hybrid (Y2H) screens were combined with true homology modeling methods to generate a high-density map of human E2/E3-RING interactions |
| GO:0005515 protein binding | IPI PMID:19549727 Analysis of the human E2 ubiquitin conjugating enzyme protei... | MODIFY | Summary: IPI binding of UBE2L6 to DTX3 (RING E3) (PMID:19549727). UBE2L6 is an E2 that is recruited by HECT, RBR and some RING E3 ligases; this interaction is an E2-E3 pairing. Reason: Bare protein binding is uninformative. The partner is a ubiquitin ligase, and E2-E3 pairing is the functional basis of UBE2L6 activity (E3s such as E6AP, Staring, Dorfin, p53RFP and NKLAM recruit UbcH8 and use it for substrate ubiquitination), so the informative term is ubiquitin protein ligase binding. This does not assert that every high-throughput pair is functional in vivo. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:19549727 yeast two-hybrid (Y2H) screens were combined with true homology modeling methods to generate a high-density map of human E2/E3-RING interactions |
| GO:0005515 protein binding | IPI PMID:19549727 Analysis of the human E2 ubiquitin conjugating enzyme protei... | MODIFY | Summary: IPI binding of UBE2L6 to RBCK1/HOIL-1 (RBR E3, LUBAC) (PMID:19549727). UBE2L6 is an E2 that is recruited by HECT, RBR and some RING E3 ligases; this interaction is an E2-E3 pairing. Reason: Bare protein binding is uninformative. The partner is a ubiquitin ligase, and E2-E3 pairing is the functional basis of UBE2L6 activity (E3s such as E6AP, Staring, Dorfin, p53RFP and NKLAM recruit UbcH8 and use it for substrate ubiquitination), so the informative term is ubiquitin protein ligase binding. This does not assert that every high-throughput pair is functional in vivo. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:19549727 yeast two-hybrid (Y2H) screens were combined with true homology modeling methods to generate a high-density map of human E2/E3-RING interactions |
| GO:0005515 protein binding | IPI PMID:19549727 Analysis of the human E2 ubiquitin conjugating enzyme protei... | MODIFY | Summary: IPI binding of UBE2L6 to TRIM8 (RING E3) (PMID:19549727). UBE2L6 is an E2 that is recruited by HECT, RBR and some RING E3 ligases; this interaction is an E2-E3 pairing. Reason: Bare protein binding is uninformative. The partner is a ubiquitin ligase, and E2-E3 pairing is the functional basis of UBE2L6 activity (E3s such as E6AP, Staring, Dorfin, p53RFP and NKLAM recruit UbcH8 and use it for substrate ubiquitination), so the informative term is ubiquitin protein ligase binding. This does not assert that every high-throughput pair is functional in vivo. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:19549727 yeast two-hybrid (Y2H) screens were combined with true homology modeling methods to generate a high-density map of human E2/E3-RING interactions |
| GO:0005515 protein binding | IPI PMID:19690564 A comprehensive framework of E2-RING E3 interactions of the ... | MODIFY | Summary: IPI binding of UBE2L6 to RNF144B/p53RFP (RBR E3) (PMID:19690564). UBE2L6 is an E2 that is recruited by HECT, RBR and some RING E3 ligases; this interaction is an E2-E3 pairing. Reason: Bare protein binding is uninformative. The partner is a ubiquitin ligase, and E2-E3 pairing is the functional basis of UBE2L6 activity (E3s such as E6AP, Staring, Dorfin, p53RFP and NKLAM recruit UbcH8 and use it for substrate ubiquitination), so the informative term is ubiquitin protein ligase binding. This does not assert that every high-throughput pair is functional in vivo. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:19690564 We performed a global yeast-two hybrid screen to study the specificity of interactions between catalytic domains of the 35 human E2s with 250 RING-type E3s. |
| GO:0005515 protein binding | IPI PMID:24446487 E2~Ub conjugates regulate the kinase activity of Shigella ef... | REMOVE | Summary: Shigella flexneri effector kinase OspG binds E2~ubiquitin conjugates including UbcH8 during infection (PMID:24446487). Reason: Generic protein binding is uninformative; the interaction is a pathogen effector exploiting host E2~Ub conjugates and describes no UBE2L6 function. Removal does not dispute the interaction. Supporting Evidence: PMID:24446487 Mass spectrometry analysis of YFP-immunoprecipitates identified UbcH5b (Ube2D2), UbcH5c (Ube2D3), Ube2E1, UbcH7 (Ube2L3), and UbcH8 (Ube2L6) as OspG-associated E2s |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: IPI binding of UBE2L6 to ARIH2/TRIAD1 (RBR E3) (PMID:25416956). UBE2L6 is an E2 that is recruited by HECT, RBR and some RING E3 ligases; this interaction is an E2-E3 pairing. Reason: Bare protein binding is uninformative. The partner is a ubiquitin ligase, and E2-E3 pairing is the functional basis of UBE2L6 activity (E3s such as E6AP, Staring, Dorfin, p53RFP and NKLAM recruit UbcH8 and use it for substrate ubiquitination), so the informative term is ubiquitin protein ligase binding. This does not assert that every high-throughput pair is functional in vivo. Proposed replacements: ubiquitin protein ligase binding |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: IPI binding of UBE2L6 to LONRF1 (RING E3) (PMID:25416956). UBE2L6 is an E2 that is recruited by HECT, RBR and some RING E3 ligases; this interaction is an E2-E3 pairing. Reason: Bare protein binding is uninformative. The partner is a ubiquitin ligase, and E2-E3 pairing is the functional basis of UBE2L6 activity (E3s such as E6AP, Staring, Dorfin, p53RFP and NKLAM recruit UbcH8 and use it for substrate ubiquitination), so the informative term is ubiquitin protein ligase binding. This does not assert that every high-throughput pair is functional in vivo. Proposed replacements: ubiquitin protein ligase binding |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: IPI binding of UBE2L6 to RBCK1/HOIL-1 (RBR E3, LUBAC) (PMID:25416956). UBE2L6 is an E2 that is recruited by HECT, RBR and some RING E3 ligases; this interaction is an E2-E3 pairing. Reason: Bare protein binding is uninformative. The partner is a ubiquitin ligase, and E2-E3 pairing is the functional basis of UBE2L6 activity (E3s such as E6AP, Staring, Dorfin, p53RFP and NKLAM recruit UbcH8 and use it for substrate ubiquitination), so the informative term is ubiquitin protein ligase binding. This does not assert that every high-throughput pair is functional in vivo. Proposed replacements: ubiquitin protein ligase binding |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MODIFY | Summary: IPI binding of UBE2L6 to ARIH2/TRIAD1 (RBR E3) (PMID:31515488). UBE2L6 is an E2 that is recruited by HECT, RBR and some RING E3 ligases; this interaction is an E2-E3 pairing. Reason: Bare protein binding is uninformative. The partner is a ubiquitin ligase, and E2-E3 pairing is the functional basis of UBE2L6 activity (E3s such as E6AP, Staring, Dorfin, p53RFP and NKLAM recruit UbcH8 and use it for substrate ubiquitination), so the informative term is ubiquitin protein ligase binding. This does not assert that every high-throughput pair is functional in vivo. Proposed replacements: ubiquitin protein ligase binding |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: IPI binding of UBE2L6 to MID1/TRIM18 (RING E3) (PMID:32296183). UBE2L6 is an E2 that is recruited by HECT, RBR and some RING E3 ligases; this interaction is an E2-E3 pairing. Reason: Bare protein binding is uninformative. The partner is a ubiquitin ligase, and E2-E3 pairing is the functional basis of UBE2L6 activity (E3s such as E6AP, Staring, Dorfin, p53RFP and NKLAM recruit UbcH8 and use it for substrate ubiquitination), so the informative term is ubiquitin protein ligase binding. This does not assert that every high-throughput pair is functional in vivo. Proposed replacements: ubiquitin protein ligase binding |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: IPI binding of UBE2L6 to ARIH2/TRIAD1 (RBR E3) (PMID:32296183). UBE2L6 is an E2 that is recruited by HECT, RBR and some RING E3 ligases; this interaction is an E2-E3 pairing. Reason: Bare protein binding is uninformative. The partner is a ubiquitin ligase, and E2-E3 pairing is the functional basis of UBE2L6 activity (E3s such as E6AP, Staring, Dorfin, p53RFP and NKLAM recruit UbcH8 and use it for substrate ubiquitination), so the informative term is ubiquitin protein ligase binding. This does not assert that every high-throughput pair is functional in vivo. Proposed replacements: ubiquitin protein ligase binding |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: IPI binding of UBE2L6 to LONRF1 (RING E3) (PMID:32296183). UBE2L6 is an E2 that is recruited by HECT, RBR and some RING E3 ligases; this interaction is an E2-E3 pairing. Reason: Bare protein binding is uninformative. The partner is a ubiquitin ligase, and E2-E3 pairing is the functional basis of UBE2L6 activity (E3s such as E6AP, Staring, Dorfin, p53RFP and NKLAM recruit UbcH8 and use it for substrate ubiquitination), so the informative term is ubiquitin protein ligase binding. This does not assert that every high-throughput pair is functional in vivo. Proposed replacements: ubiquitin protein ligase binding |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: IPI binding of UBE2L6 to DTX3 (RING E3) (PMID:32296183). UBE2L6 is an E2 that is recruited by HECT, RBR and some RING E3 ligases; this interaction is an E2-E3 pairing. Reason: Bare protein binding is uninformative. The partner is a ubiquitin ligase, and E2-E3 pairing is the functional basis of UBE2L6 activity (E3s such as E6AP, Staring, Dorfin, p53RFP and NKLAM recruit UbcH8 and use it for substrate ubiquitination), so the informative term is ubiquitin protein ligase binding. This does not assert that every high-throughput pair is functional in vivo. Proposed replacements: ubiquitin protein ligase binding |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: IPI binding of UBE2L6 to TRIM62 (RING E3) (PMID:32296183). UBE2L6 is an E2 that is recruited by HECT, RBR and some RING E3 ligases; this interaction is an E2-E3 pairing. Reason: Bare protein binding is uninformative. The partner is a ubiquitin ligase, and E2-E3 pairing is the functional basis of UBE2L6 activity (E3s such as E6AP, Staring, Dorfin, p53RFP and NKLAM recruit UbcH8 and use it for substrate ubiquitination), so the informative term is ubiquitin protein ligase binding. This does not assert that every high-throughput pair is functional in vivo. Proposed replacements: ubiquitin protein ligase binding |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: IPI binding of UBE2L6 to RBCK1/HOIL-1 (RBR E3, LUBAC) (PMID:32296183). UBE2L6 is an E2 that is recruited by HECT, RBR and some RING E3 ligases; this interaction is an E2-E3 pairing. Reason: Bare protein binding is uninformative. The partner is a ubiquitin ligase, and E2-E3 pairing is the functional basis of UBE2L6 activity (E3s such as E6AP, Staring, Dorfin, p53RFP and NKLAM recruit UbcH8 and use it for substrate ubiquitination), so the informative term is ubiquitin protein ligase binding. This does not assert that every high-throughput pair is functional in vivo. Proposed replacements: ubiquitin protein ligase binding |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: IPI binding of UBE2L6 to TRIM8 (RING E3) (PMID:32296183). UBE2L6 is an E2 that is recruited by HECT, RBR and some RING E3 ligases; this interaction is an E2-E3 pairing. Reason: Bare protein binding is uninformative. The partner is a ubiquitin ligase, and E2-E3 pairing is the functional basis of UBE2L6 activity (E3s such as E6AP, Staring, Dorfin, p53RFP and NKLAM recruit UbcH8 and use it for substrate ubiquitination), so the informative term is ubiquitin protein ligase binding. This does not assert that every high-throughput pair is functional in vivo. Proposed replacements: ubiquitin protein ligase binding |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: IPI binding of UBE2L6 to RNF216/TRIAD3 (RBR E3) (PMID:32296183). UBE2L6 is an E2 that is recruited by HECT, RBR and some RING E3 ligases; this interaction is an E2-E3 pairing. Reason: Bare protein binding is uninformative. The partner is a ubiquitin ligase, and E2-E3 pairing is the functional basis of UBE2L6 activity (E3s such as E6AP, Staring, Dorfin, p53RFP and NKLAM recruit UbcH8 and use it for substrate ubiquitination), so the informative term is ubiquitin protein ligase binding. This does not assert that every high-throughput pair is functional in vivo. Proposed replacements: ubiquitin protein ligase binding |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput interactome detection of UBE2L6 with GNB2 (PMID:32814053). Reason: Generic protein binding is uninformative and GNB2 is not a ubiquitin ligase, so no more informative molecular function can be assigned from this screen. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput interactome detection of UBE2L6 with LITAF (PMID:32814053). Reason: Generic protein binding is uninformative and LITAF is not a ubiquitin ligase, so no more informative molecular function can be assigned from this screen. Removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: IPI binding of UBE2L6 to ARIH2/TRIAD1 (RBR E3) (PMID:33961781). UBE2L6 is an E2 that is recruited by HECT, RBR and some RING E3 ligases; this interaction is an E2-E3 pairing. Reason: Bare protein binding is uninformative. The partner is a ubiquitin ligase, and E2-E3 pairing is the functional basis of UBE2L6 activity (E3s such as E6AP, Staring, Dorfin, p53RFP and NKLAM recruit UbcH8 and use it for substrate ubiquitination), so the informative term is ubiquitin protein ligase binding. This does not assert that every high-throughput pair is functional in vivo. Proposed replacements: ubiquitin protein ligase binding |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5653754 | KEEP AS NON CORE | Summary: Reactome TAS (Reactome:R-HSA-5653754) for TRIM25-mediated ISGylation of monoubiquitinated PCNA, placing UBE2L6 in the nucleoplasm. Reason: UBE2L6 is a small soluble E2 and its ISG15 and ubiquitin conjugation activities are largely cytosolic, but Reactome curates a nuclear reaction (UBE2L6:TRIM25 ISGylation of PCNA) based on Park et al. 2014. Nucleoplasm is plausible as a secondary location. Supporting Evidence: Reactome:R-HSA-5653754 The complex of ISG15 E2 conjugating enzyme UBE2L6 (UBCH8) and ISG15 E3 conjugating enzyme TRIM25 (EFP) doubly ISGylates monoubiquitinated PCNA (MonoUb:K164-PCNA) on lysine residues K164 and K168. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5653756 | KEEP AS NON CORE | Summary: Reactome TAS (Reactome:R-HSA-5653756) for TRIM25-mediated ISGylation of monoubiquitinated PCNA, placing UBE2L6 in the nucleoplasm. Reason: UBE2L6 is a small soluble E2 and its ISG15 and ubiquitin conjugation activities are largely cytosolic, but Reactome curates a nuclear reaction (UBE2L6:TRIM25 ISGylation of PCNA) based on Park et al. 2014. Nucleoplasm is plausible as a secondary location. Supporting Evidence: Reactome:R-HSA-5653754 The complex of ISG15 E2 conjugating enzyme UBE2L6 (UBCH8) and ISG15 E3 conjugating enzyme TRIM25 (EFP) doubly ISGylates monoubiquitinated PCNA (MonoUb:K164-PCNA) on lysine residues K164 and K168. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | MODIFY | Summary: IBA (PTN008604282) placing E2s of this clade in the cytoplasm. Reason: Correct but general. UBE2L6 is a soluble E2 whose ISG15 and ubiquitin conjugation reactions are curated in the cytosol (multiple Reactome reactions); the descendant GO:0005829 cytosol, which the gene already carries, is the more specific location. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN008604282 SUPPORTS TRANSFER E2 clade node for cytoplasmic activity; correct for UBE2L6, which is refined to cytosol. Proposed replacements: cytosol Supporting Evidence: Reactome:R-HSA-1169404 Activated ISG15 linked to UBE1L is transferred to the E2 conjugating enzyme UBCH8. |
| GO:0005737 cytoplasm | IC PMID:16009940 Human ISG15 conjugation targets both IFN-induced and constit... | MODIFY | Summary: IC from the ISG15 target proteomics paper (PMID:16009940), inferred from cytoplasmic ISGylation targets. Reason: Correct but general. UBE2L6 is a soluble E2 whose ISG15 and ubiquitin conjugation reactions are curated in the cytosol (multiple Reactome reactions); the descendant GO:0005829 cytosol, which the gene already carries, is the more specific location. Proposed replacements: cytosol Supporting Evidence: PMID:16009940 Our system for the identification of ISG15 target proteins was based on the transfection of plasmids expressing a double-affinity-tagged ISG15, Ube1L/E1 ISG15 , and UbcH8 into human (HeLa) cells. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1169394 | ACCEPT | Summary: Reactome TAS (Reactome:R-HSA-1169394) placing UBE2L6-dependent ISG15 or ubiquitin transfer reactions in the cytosol. Reason: UBE2L6 is a soluble E2 enzyme, and the bulk of ISG15 conjugation (E1 UBA7 to E2 transfer and ISGylation of cytosolic antiviral targets such as RIG-I, PKR and MxA) and its SIAH1-dependent ubiquitination of SNCA are cytosolic reactions. Supporting Evidence: Reactome:R-HSA-1169404 Activated ISG15 linked to UBE1L is transferred to the E2 conjugating enzyme UBCH8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1169395 | ACCEPT | Summary: Reactome TAS (Reactome:R-HSA-1169395) placing UBE2L6-dependent ISG15 or ubiquitin transfer reactions in the cytosol. Reason: UBE2L6 is a soluble E2 enzyme, and the bulk of ISG15 conjugation (E1 UBA7 to E2 transfer and ISGylation of cytosolic antiviral targets such as RIG-I, PKR and MxA) and its SIAH1-dependent ubiquitination of SNCA are cytosolic reactions. Supporting Evidence: Reactome:R-HSA-1169404 Activated ISG15 linked to UBE1L is transferred to the E2 conjugating enzyme UBCH8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1169398 | ACCEPT | Summary: Reactome TAS (Reactome:R-HSA-1169398) placing UBE2L6-dependent ISG15 or ubiquitin transfer reactions in the cytosol. Reason: UBE2L6 is a soluble E2 enzyme, and the bulk of ISG15 conjugation (E1 UBA7 to E2 transfer and ISGylation of cytosolic antiviral targets such as RIG-I, PKR and MxA) and its SIAH1-dependent ubiquitination of SNCA are cytosolic reactions. Supporting Evidence: Reactome:R-HSA-1169404 Activated ISG15 linked to UBE1L is transferred to the E2 conjugating enzyme UBCH8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1169402 | ACCEPT | Summary: Reactome TAS (Reactome:R-HSA-1169402) placing UBE2L6-dependent ISG15 or ubiquitin transfer reactions in the cytosol. Reason: UBE2L6 is a soluble E2 enzyme, and the bulk of ISG15 conjugation (E1 UBA7 to E2 transfer and ISGylation of cytosolic antiviral targets such as RIG-I, PKR and MxA) and its SIAH1-dependent ubiquitination of SNCA are cytosolic reactions. Supporting Evidence: Reactome:R-HSA-1169404 Activated ISG15 linked to UBE1L is transferred to the E2 conjugating enzyme UBCH8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1169403 | ACCEPT | Summary: Reactome TAS (Reactome:R-HSA-1169403) placing UBE2L6-dependent ISG15 or ubiquitin transfer reactions in the cytosol. Reason: UBE2L6 is a soluble E2 enzyme, and the bulk of ISG15 conjugation (E1 UBA7 to E2 transfer and ISGylation of cytosolic antiviral targets such as RIG-I, PKR and MxA) and its SIAH1-dependent ubiquitination of SNCA are cytosolic reactions. Supporting Evidence: Reactome:R-HSA-1169404 Activated ISG15 linked to UBE1L is transferred to the E2 conjugating enzyme UBCH8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1169404 | ACCEPT | Summary: Reactome TAS (Reactome:R-HSA-1169404) placing UBE2L6-dependent ISG15 or ubiquitin transfer reactions in the cytosol. Reason: UBE2L6 is a soluble E2 enzyme, and the bulk of ISG15 conjugation (E1 UBA7 to E2 transfer and ISGylation of cytosolic antiviral targets such as RIG-I, PKR and MxA) and its SIAH1-dependent ubiquitination of SNCA are cytosolic reactions. Supporting Evidence: Reactome:R-HSA-1169404 Activated ISG15 linked to UBE1L is transferred to the E2 conjugating enzyme UBCH8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1169405 | ACCEPT | Summary: Reactome TAS (Reactome:R-HSA-1169405) placing UBE2L6-dependent ISG15 or ubiquitin transfer reactions in the cytosol. Reason: UBE2L6 is a soluble E2 enzyme, and the bulk of ISG15 conjugation (E1 UBA7 to E2 transfer and ISGylation of cytosolic antiviral targets such as RIG-I, PKR and MxA) and its SIAH1-dependent ubiquitination of SNCA are cytosolic reactions. Supporting Evidence: Reactome:R-HSA-1169404 Activated ISG15 linked to UBE1L is transferred to the E2 conjugating enzyme UBCH8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1169406 | ACCEPT | Summary: Reactome TAS (Reactome:R-HSA-1169406) placing UBE2L6-dependent ISG15 or ubiquitin transfer reactions in the cytosol. Reason: UBE2L6 is a soluble E2 enzyme, and the bulk of ISG15 conjugation (E1 UBA7 to E2 transfer and ISGylation of cytosolic antiviral targets such as RIG-I, PKR and MxA) and its SIAH1-dependent ubiquitination of SNCA are cytosolic reactions. Supporting Evidence: Reactome:R-HSA-1169404 Activated ISG15 linked to UBE1L is transferred to the E2 conjugating enzyme UBCH8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1678843 | ACCEPT | Summary: Reactome TAS (Reactome:R-HSA-1678843) placing UBE2L6-dependent ISG15 or ubiquitin transfer reactions in the cytosol. Reason: UBE2L6 is a soluble E2 enzyme, and the bulk of ISG15 conjugation (E1 UBA7 to E2 transfer and ISGylation of cytosolic antiviral targets such as RIG-I, PKR and MxA) and its SIAH1-dependent ubiquitination of SNCA are cytosolic reactions. Supporting Evidence: Reactome:R-HSA-1169404 Activated ISG15 linked to UBE1L is transferred to the E2 conjugating enzyme UBCH8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5658496 | ACCEPT | Summary: Reactome TAS (Reactome:R-HSA-5658496) placing UBE2L6-dependent ISG15 or ubiquitin transfer reactions in the cytosol. Reason: UBE2L6 is a soluble E2 enzyme, and the bulk of ISG15 conjugation (E1 UBA7 to E2 transfer and ISGylation of cytosolic antiviral targets such as RIG-I, PKR and MxA) and its SIAH1-dependent ubiquitination of SNCA are cytosolic reactions. Supporting Evidence: Reactome:R-HSA-1169404 Activated ISG15 linked to UBE1L is transferred to the E2 conjugating enzyme UBCH8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5660753 | ACCEPT | Summary: Reactome TAS (Reactome:R-HSA-5660753) placing UBE2L6-dependent ISG15 or ubiquitin transfer reactions in the cytosol. Reason: UBE2L6 is a soluble E2 enzyme, and the bulk of ISG15 conjugation (E1 UBA7 to E2 transfer and ISGylation of cytosolic antiviral targets such as RIG-I, PKR and MxA) and its SIAH1-dependent ubiquitination of SNCA are cytosolic reactions. Supporting Evidence: Reactome:R-HSA-5660753 SIAH1 transfers ubiquitin from UBE2L6 to SNCA, generating monoubiquitinated SNCA (Ub-SNCA) |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5660757 | ACCEPT | Summary: Reactome TAS (Reactome:R-HSA-5660757) placing UBE2L6-dependent ISG15 or ubiquitin transfer reactions in the cytosol. Reason: UBE2L6 is a soluble E2 enzyme, and the bulk of ISG15 conjugation (E1 UBA7 to E2 transfer and ISGylation of cytosolic antiviral targets such as RIG-I, PKR and MxA) and its SIAH1-dependent ubiquitination of SNCA are cytosolic reactions. Supporting Evidence: Reactome:R-HSA-1169404 Activated ISG15 linked to UBE1L is transferred to the E2 conjugating enzyme UBCH8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-936563 | ACCEPT | Summary: Reactome TAS (Reactome:R-HSA-936563) placing UBE2L6-dependent ISG15 or ubiquitin transfer reactions in the cytosol. Reason: UBE2L6 is a soluble E2 enzyme, and the bulk of ISG15 conjugation (E1 UBA7 to E2 transfer and ISGylation of cytosolic antiviral targets such as RIG-I, PKR and MxA) and its SIAH1-dependent ubiquitination of SNCA are cytosolic reactions. Supporting Evidence: Reactome:R-HSA-1169404 Activated ISG15 linked to UBE1L is transferred to the E2 conjugating enzyme UBCH8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9833973 | ACCEPT | Summary: Reactome TAS (Reactome:R-HSA-9833973) placing UBE2L6-dependent ISG15 or ubiquitin transfer reactions in the cytosol. Reason: UBE2L6 is a soluble E2 enzyme, and the bulk of ISG15 conjugation (E1 UBA7 to E2 transfer and ISGylation of cytosolic antiviral targets such as RIG-I, PKR and MxA) and its SIAH1-dependent ubiquitination of SNCA are cytosolic reactions. Supporting Evidence: Reactome:R-HSA-1169404 Activated ISG15 linked to UBE1L is transferred to the E2 conjugating enzyme UBCH8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9837231 | ACCEPT | Summary: Reactome TAS (Reactome:R-HSA-9837231) placing UBE2L6-dependent ISG15 or ubiquitin transfer reactions in the cytosol. Reason: UBE2L6 is a soluble E2 enzyme, and the bulk of ISG15 conjugation (E1 UBA7 to E2 transfer and ISGylation of cytosolic antiviral targets such as RIG-I, PKR and MxA) and its SIAH1-dependent ubiquitination of SNCA are cytosolic reactions. Supporting Evidence: Reactome:R-HSA-1169404 Activated ISG15 linked to UBE1L is transferred to the E2 conjugating enzyme UBCH8. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9927247 | ACCEPT | Summary: Reactome TAS (Reactome:R-HSA-9927247) placing UBE2L6-dependent ISG15 or ubiquitin transfer reactions in the cytosol. Reason: UBE2L6 is a soluble E2 enzyme, and the bulk of ISG15 conjugation (E1 UBA7 to E2 transfer and ISGylation of cytosolic antiviral targets such as RIG-I, PKR and MxA) and its SIAH1-dependent ubiquitination of SNCA are cytosolic reactions. Supporting Evidence: Reactome:R-HSA-1169404 Activated ISG15 linked to UBE1L is transferred to the E2 conjugating enzyme UBCH8. |
| GO:0006511 ubiquitin-dependent protein catabolic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA from PTN000631055 (UBE2L3/UBE2L6 class). Human UbcH8 cooperates with E3s that target substrates for proteasomal degradation (Staring/syntaxin 1, SIAH1/FLT3-ITD). Reason: UBE2L6 performs the E2 step of ubiquitination that marks substrates for proteasomal degradation, and it sits in the PAINT clade carrying this term. The evidence is substrate-specific and secondary to its ISG15 E2 role; ISGylation itself does not generally promote degradation. Supporting Evidence: PMID:12121982 Staring binds and recruits the brain-enriched E2 ubiquitin-conjugating enzyme UbcH8 to syntaxin 1 and facilitates the ubiquitination and proteasome-dependent degradation of syntaxin 1. PMID:20508617 UBCH8 and the ubiquitin-ligase SIAH1 physically interact with and target FLT3-ITD for proteasomal degradation |
| GO:0016567 protein ubiquitination | IEA GO_REF:0000041 | MODIFY | Summary: IEA from UniPathway mapping (protein ubiquitination pathway). Reason: True but general; the gene already carries the more specific descendant GO:0000209 protein polyubiquitination, supported by UbcH8-dependent HECT polyubiquitination. Proposed replacements: protein polyubiquitination Supporting Evidence: PMID:15131269 Rsp5p catalyzed efficient polyubiquitination of WBP2 in the presence of E1 Ub and UbcH8 |
| GO:0019787 ubiquitin-like protein transferase activity | IEA GO_REF:0000107 | MODIFY | Summary: IEA by Ensembl Compara transfer from mouse Ube2l6 (Q9QZU9). Reason: Correct but general. UBE2L6 is an E2 for both ISG15 and ubiquitin; the specific descendants GO:0061653 ISG15 conjugating enzyme activity and GO:0061631 ubiquitin conjugating enzyme activity are both carried and experimentally supported in human. Proposed replacements: ISG15 conjugating enzyme activity ubiquitin conjugating enzyme activity Supporting Evidence: PMID:15131269 Here we report the purification of an E2 enzyme for ISG15 and demonstrate that it is UbcH8, an E2 that also functions in Ub conjugation. |
| GO:0032020 ISG15-protein conjugation | IBA GO_REF:0000033 | ACCEPT | Summary: UBE2L6 is the major E2 of the ISG15 conjugation cascade (UBA7 E1 -> UBE2L6 E2 -> HERC5/TRIM25/ARIH1 E3s). IBA from PAINT node PTN000631065 (Mammalia), seeded by human UBE2L6 and mouse Ube2l6. Reason: Core process. Human UBE2L6 was purified as the E2 charged by E1(ISG15), transfers ISG15 in vitro, and its knockdown reduces IFN-induced ISGylation in HeLa cells (two independent studies). The IBA reflects the PAINT judgment that this is an inherited mammalian UBE2L6 function; the target's own appearance among the seeds marks its experimental grounding. Supporting Evidence: PMID:15131269 UbcH8 serves as a major E2 enzyme for ISG15 conjugation in vivo PMID:15485925 The reduction of Ubc8 expression by small interfering RNA causes a decrease in protein ISGylation in HeLa cells upon interferon treatment. |
| GO:0032020 ISG15-protein conjugation | IDA PMID:15131269 The UbcH8 ubiquitin E2 enzyme is also the E2 enzyme for ISG1... | ACCEPT | Summary: UBE2L6 is the major E2 of the ISG15 conjugation cascade (UBA7 E1 -> UBE2L6 E2 -> HERC5/TRIM25/ARIH1 E3s). IDA: purification from IFN-treated cells, in vitro transfer and siRNA knockdown (PMID:15131269). Reason: Core process. Human UBE2L6 was purified as the E2 charged by E1(ISG15), transfers ISG15 in vitro, and its knockdown reduces IFN-induced ISGylation in HeLa cells (two independent studies). The IBA reflects the PAINT judgment that this is an inherited mammalian UBE2L6 function; the target's own appearance among the seeds marks its experimental grounding. Supporting Evidence: PMID:15131269 UbcH8 serves as a major E2 enzyme for ISG15 conjugation in vivo PMID:15485925 The reduction of Ubc8 expression by small interfering RNA causes a decrease in protein ISGylation in HeLa cells upon interferon treatment. |
| GO:0032446 protein modification by small protein conjugation | IEA GO_REF:0000117 | MODIFY | Summary: IEA from ARBA machine-learning rule. Reason: Correct but general. UBE2L6 conjugates two specific small proteins; the descendants GO:0032020 ISG15-protein conjugation and GO:0000209 protein polyubiquitination, both carried, should be used. Proposed replacements: ISG15-protein conjugation protein polyubiquitination Supporting Evidence: PMID:15131269 Here we report the purification of an E2 enzyme for ISG15 and demonstrate that it is UbcH8, an E2 that also functions in Ub conjugation. |
| GO:0036211 protein modification process | TAS PMID:9153201 Physical interaction between specific E2 and Hect E3 enzymes... | MODIFY | Summary: TAS from PMID:9153201 (UbcH8 cloning, E6AP cooperation). Reason: Correct but very general. The modification UBE2L6 performs is ubiquitin or ISG15 conjugation; the carried descendants GO:0000209 protein polyubiquitination and GO:0032020 ISG15-protein conjugation are informative. Proposed replacements: protein polyubiquitination ISG15-protein conjugation Supporting Evidence: PMID:9153201 only the E6AP-interacting E2s could function in conjunction with E6AP in the ubiquitination of an E6 independent substrate of E6AP |
| GO:0042296 ISG15 transferase activity | IBA GO_REF:0000033 | MODIFY | Summary: IBA from PAINT node PTN000631065 (Mammalia; seeds human UBE2L6 and mouse Ube2l6). UBE2L6 accepts ISG15 from UBA7 on its active-site cysteine and passes it to E3 ligases. Reason: The activity is correct and experimentally established for human UBE2L6, but GO:0042296 ISG15 transferase activity is the general parent; the E2-specific descendant GO:0061653 ISG15 conjugating enzyme activity (carried by EXP evidence) describes exactly what UBE2L6 does (thioester transfer from E1, not E3-type ligation). This refines rather than disputes the PAINT node. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000631065 SUPPORTS TRANSFER Mammalian UBE2L6 node seeded by human UBE2L6 and mouse Ube2l6 experiments; the transfer is sound, only the term is the general parent of the E2-specific GO:0061653. Proposed replacements: ISG15 conjugating enzyme activity Supporting Evidence: PMID:15131269 These results indicate that ISG15 was transferred from E1 ISG15 to UbcH8, and that UbcH8 functions as an E2 for ISG15. |
| GO:0042296 ISG15 transferase activity | IDA PMID:15131269 The UbcH8 ubiquitin E2 enzyme is also the E2 enzyme for ISG1... | MODIFY | Summary: IDA from PMID:15131269: E1(ISG15)-dependent formation of the UbcH8~ISG15 thioester with purified proteins. UBE2L6 accepts ISG15 from UBA7 on its active-site cysteine and passes it to E3 ligases. Reason: The activity is correct and experimentally established for human UBE2L6, but GO:0042296 ISG15 transferase activity is the general parent; the E2-specific descendant GO:0061653 ISG15 conjugating enzyme activity (carried by EXP evidence) describes exactly what UBE2L6 does (thioester transfer from E1, not E3-type ligation). This refines rather than disputes the PAINT node. Proposed replacements: ISG15 conjugating enzyme activity Supporting Evidence: PMID:15131269 These results indicate that ISG15 was transferred from E1 ISG15 to UbcH8, and that UbcH8 functions as an E2 for ISG15. |
| GO:0042296 ISG15 transferase activity | IEA GO_REF:0000107 | MODIFY | Summary: IEA by Ensembl Compara transfer from mouse Ube2l6. UBE2L6 accepts ISG15 from UBA7 on its active-site cysteine and passes it to E3 ligases. Reason: The activity is correct and experimentally established for human UBE2L6, but GO:0042296 ISG15 transferase activity is the general parent; the E2-specific descendant GO:0061653 ISG15 conjugating enzyme activity (carried by EXP evidence) describes exactly what UBE2L6 does (thioester transfer from E1, not E3-type ligation). This refines rather than disputes the PAINT node. Proposed replacements: ISG15 conjugating enzyme activity Supporting Evidence: PMID:15131269 These results indicate that ISG15 was transferred from E1 ISG15 to UbcH8, and that UbcH8 functions as an E2 for ISG15. |
| GO:0045087 innate immune response | IDA PMID:28724761 ISG15 Modulates Type I Interferon Signaling and the Antivira... | KEEP AS NON CORE | Summary: IDA from a hepatitis E virus study (PMID:28724761) in which UBE2L6 knockdown was tested alongside ISG15 and UBE1L. Reason: UBE2L6 catalyses a step of IFN-induced ISGylation, which modifies antiviral effectors such as RIG-I, MxA and PKR, so involvement in the innate immune response is defensible at a broad level. However, the cited paper itself found UBE2L6 loss did not alter HEV interferon sensitivity, so the evidence for UBE2L6 specifically is weak and the term is not core. Supporting Evidence: PMID:28724761 We also observed that loss of ISGylating enzymes (UBE1L and UBE2L6) did not affect the HEV type I IFN sensitivity. PMID:16009940 Several of the targets are IFN-Ξ±/Ξ²-induced antiviral proteins, providing a rationale for the inhibition of ISG15 conjugation by influenza B virus. |
| GO:0061631 ubiquitin conjugating enzyme activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from deep E2 node PTN002514495. UBE2L6 is charged with ubiquitin by E1 and works with HECT (E6AP), RBR (Dorfin, p53RFP, NKLAM) and RING (Staring, SIAH1) ligases. Reason: Core activity. UbcH8 was cloned as an E6AP partner and supports E6AP- and Rsp5-dependent ubiquitination; it has the canonical UBC fold with active-site Cys86. UBE2L6 lies within the E2 clade PAINT annotated with this activity. Supporting Evidence: PMID:9153201 only the E6AP-interacting E2s could function in conjunction with E6AP in the ubiquitination of an E6 independent substrate of E6AP PMID:15131269 Rsp5p catalyzed efficient polyubiquitination of WBP2 in the presence of E1 Ub and UbcH8 |
| GO:0061631 ubiquitin conjugating enzyme activity | IEA GO_REF:0000003 | ACCEPT | Summary: IEA from EC 2.3.2.23 mapping. UBE2L6 is charged with ubiquitin by E1 and works with HECT (E6AP), RBR (Dorfin, p53RFP, NKLAM) and RING (Staring, SIAH1) ligases. Reason: Core activity. UbcH8 was cloned as an E6AP partner and supports E6AP- and Rsp5-dependent ubiquitination; it has the canonical UBC fold with active-site Cys86. UBE2L6 lies within the E2 clade PAINT annotated with this activity. Supporting Evidence: PMID:9153201 only the E6AP-interacting E2s could function in conjunction with E6AP in the ubiquitination of an E6 independent substrate of E6AP PMID:15131269 Rsp5p catalyzed efficient polyubiquitination of WBP2 in the presence of E1 Ub and UbcH8 |
| GO:0061650 ubiquitin-like protein conjugating enzyme activity | IEA GO_REF:0000117 | MODIFY | Summary: IEA from ARBA machine-learning rule. Reason: Correct but general; both specific descendants GO:0061653 ISG15 conjugating enzyme activity and GO:0061631 ubiquitin conjugating enzyme activity are carried and experimentally supported. Proposed replacements: ISG15 conjugating enzyme activity ubiquitin conjugating enzyme activity Supporting Evidence: PMID:15131269 Here we report the purification of an E2 enzyme for ISG15 and demonstrate that it is UbcH8, an E2 that also functions in Ub conjugation. |
| GO:0061653 ISG15 conjugating enzyme activity | EXP PMID:15485925 Interferon-inducible ubiquitin E2, Ubc8, is a conjugating en... | ACCEPT | Summary: EXP from PMID:15485925: Ubc8 mediates ISGylation in transfection assays and its siRNA knockdown reduces IFN-induced ISGylation in HeLa cells; UbcH7 and Ubc9 do not substitute. Reason: Core activity, established in human cells by two independent groups (PMID:15485925, PMID:15131269) with in vitro E1(ISG15)-to-UbcH8 thioester transfer. This is the most specific term for UBE2L6's ISG15 E2 function. Supporting Evidence: PMID:15485925 Ubc8 clearly mediates protein ISGylation in transfection assays. PMID:15485925 The reduction of Ubc8 expression by small interfering RNA causes a decrease in protein ISGylation in HeLa cells upon interferon treatment. PMID:15131269 These results indicate that ISG15 was transferred from E1 ISG15 to UbcH8, and that UbcH8 functions as an E2 for ISG15. |
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Download this section (compressed HTML)Q: Should PAINT node PTN000631065 be annotated with the E2-specific GO:0061653 ISG15 conjugating enzyme activity instead of the parent GO:0042296 ISG15 transferase activity?
Q: Like UBE2L3, does UBE2L6 lack intrinsic lysine reactivity (so that it functions only with HECT/RBR E3s), and does this explain why RING-only E3s rarely use it productively?
Q: What fraction of IFN-induced ISGylation in vivo is UBE2L6-dependent versus supported by other E2s, given residual ISGylation after knockdown?
Experiment: Measure ISGylation and antiviral responses in UBE2L6 knockout human cells and Ube2l6-null mice, compared with Uba7-null, to define the E2's non-redundant contribution to ISG15-mediated antiviral defence.
Experiment: Single-turnover lysine-discharge assays of UBE2L6~ubiquitin and UBE2L6~ISG15 with free lysine and with RING versus HECT/RBR E3s to determine whether UBE2L6 is lysine-unreactive like UBE2L3.
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