IndraLab

Statements

OTUB1 binds UBE2N. 100 / 112
1 17 | 41 41
sparser
"Since a UEV (ubiquitin E2 variant) must bind to UBC13 and position the acceptor ubiquitin in order for K63Ub synthesis to occur xref , we asked whether OTUB1 could bind to UBC13 in the presence of UEV1a."
22367539
sparser
"The fact that OTUB1 binds UBC13 may have affects on other UBC13 dependent E3 ligases, which could explain its pleiotropic affect on many different (indirect) substrates."
| PMC
reach
"OTUB1 binds Ubc13 (UBE2N) to inhibit K63-linked-ubiquitination of chromatin in DSB repair, whereas its ohnolog, OTUB2, shows much lower affinity for Ubc13 and instead promotes HR by interacting with another novel ohnolog, L3MBTL1."
28177072
reach
"To verify that the interactions observed in the crystal structure are also observed in solution, the binding of the E2s UbcH5c (closely related to UbcH5b and also targeted by OTUB1) and UBC13 to full-length OTUB1 was examined by NMR spectroscopy."
22325355
biogrid
No evidence text available
35927303
reach
"When we model UBC13 binding to OTUB1, the surface of UBC13 engaged by its ancillary factor UEV2 (Mms2) is not occluded significantly by OTUB1 (XREF_SUPPLEMENTARY)."
22325355
reach
"This is consistent with the observation that binding of UBC13 to UEV1A or OTUB1 is not mutually exclusive."
22325355
sparser
"OTUB1 binds Ubc13 (UBE2N) to inhibit K63-linked-ubiquitination of chromatin in DSB repair, whereas its ohnolog, OTUB2, shows much lower affinity for Ubc13 ( xref ) and instead promotes HR by interacting with another novel ohnolog, L3MBTL1 ( xref ; xref )."
28177072
sparser
"Furthermore, the atomic level information of the interaction between human OTUB1 and UBC13 has not been reported."
22679021
biogrid
No evidence text available
20725033
biogrid
No evidence text available
20725033
sparser
"OTUB1 binds to UBC13 (UBE2N), an E2 ubiquitin-conjugating enzyme for RNF168, and restricts its interaction with RNF168, suppressing the DSB responses by inhibiting RNF168-induced polyubiquitylation independently of its catalytic activity [ xref ]."
35897775
reach
"The K d for binding of UBE2N to OTUB1 was 8.1 muM, which is consistent with previous studies that measured a K d of 7.04 muM using fluorescence polarization 31 and K d of 8.9 muM measured by surface plasmon resonance using a GST-OTUB1 fusion 29."
32049508
biogrid
No evidence text available
35500217
reach
"In the late phase of DNA damage, OTUB1 directly interacts with and inhibits ubiquitin-charged Ubc13, in turn negatively regulating RNF168-dependent K63-linked polyubiquitination at the site of DNA dam[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
33609777
reach
"The Phe133 and Lys213 residues in OTUB1 contribute to the specific binding of OTUB1 to Ubc13 ( Sato et al., 2012 )."
33609777
biogrid
No evidence text available
22367539
reach
"Moreover, we demonstrated the endogenous interactions between OTUB1 and UBE2N or UBE2D1 (XREF_FIG)."
24071738
signor
"The deubiquitinating enzyme otub1 suppresses rnf168 dependent ubiquitination by direct the e2 ligase ubc13"
21763684
sparser
"Further biochemical analysis revealed that OTUB1 binds to the E2 UBC13 and prevents the ubiquitin ligase RNF168 from ubiquitinating chromatin at sites of DNA damage."
30400005
sparser
"Indeed, a different study modeling the E2 UBC13 interaction with OTUB1 found almost identical OTUB1 residues are critical for mediating an inhibitory complex ( xref )."
30400005
biogrid
No evidence text available
27909234
reach
"OTUB1 interacts with UBC13 (UBE2N) and the UBE2D and UBE2E family E2 ubiquitin conjugating enzymes and inhibits their E2 activities in a DUB activity independent manner (Nakada et al., 2010; Sato et a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24560272
reach
"In humans, OTUB1, a deubiquitinating enzyme, forms a complex in vivo with Ubc13 and prevents ubiquitin transfer (Nakada et al., 2010; Wiener et al., 2012)."
37102249
sparser
"In vitro experiments show that OTUB1 binds directly to the charged E2 Ubc13, without a requirement for its cofactor UEV1a, and inhibits isopeptide bond formation between the donor ubiquitin on Ubc13 a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
22743550
sparser
"OTUB1 preferentially binds to ubiquitylated UBC13 via its amino-terminal domain and inhibits ubiquitin-chain extension in a manner independent of its catalytic activity."
28764946
sparser
"When we model UBC13 binding to OTUB1, the surface of UBC13 engaged by its ancillary factor UEV2 (Mms2) ( xref ) is not occluded significantly by OTUB1 ( xref )."
22325355
reach
"We unexpectedly find that OTUB1 binding to UBC13 ~ Ub is allosterically regulated by free ubiquitin, which binds to a second site in OTUB1 and increases its affinity for UBC13 ~ Ub, while at the same time disrupting interactions with UEV1a in a manner that depends upon the OTUB1 N-terminus."
22367539
reach
"SET7-mediated methylation of OTUB1 attenuates OTUB1 binding to UBC13."
36822329
reach
"In addition, coimmunoprecipitation assay showed that endogenous Ubc13 bound to more endogenous Otub1 in Set7-deficient mouse embryo fibroblast (MEF) cells (Set7 ) than in Set7-intact MEF cells (Set7 ) (Fig. 6C)."
36822329
reach
"Crystal structures of an OTUB1 and UBC13 complex and of OTUB1 bound to ubiquitin aldehyde and a chemical UBC13 ~ Ub conjugate show that binding of free ubiquitin to OTUB1 triggers conformational changes in the OTU domain and formation of a ubiquitin binding helix in the N-terminus, thus promoting binding of the conjugated donor ubiquitin in UBC13 ~ Ub to OTUB1."
22367539
reach
"This prompted us to ask whether free ubiquitin binding to the OTUB1 distal site could similarly stimulate binding of OTUB1 to UBC13 ~ Ub conjugates."
22367539
reach
"Remarkably, OTUB1 shows no preference for the charged UBC13 ~ Ub in the absence of ubiquitin, whereas addition of 100 microM free ubiquitin greatly enhances OTUB1 binding to UBC13 ~ Ub, but not to uncharged UBC13 (XREF_FIG)."
22367539
reach
"By contrast, ubiquitin bearing hydrophobic patch mutations I44A, L8A or L8A/I44A/R42A (but not R42A alone) do not stimulate OTUB1 binding to UBC13 ~ Ub like wild type ubiquitin (XREF_FIG)."
22367539
reach
"Another obvious inhibitory feature of OTUB1 binding to Ubc13 ~ Ub (or E2 ~ Ub) is that it occludes and overlaps with the RING E3 binding site."
27486774
reach
"The relative binding of OTUB1 to UBC13 ~ Ub increases as the concentration of free ubiquitin is increased from 2 to 50 microM (XREF_SUPPLEMENTARY)."
22367539
reach
"Distal site substitutions F193W, F193R and H217W disrupted the ability of OTUB1 to inhibit polyubiquitination by UBC13 and UEV1a (XREF_FIG) without affecting binding of OTUB1 to UBC13 (XREF_SUPPLEMENTARY)."
22367539
reach
"Since a UEV (ubiquitin E2 variant) must bind to UBC13 and position the acceptor ubiquitin in order for K63Ub synthesis to occur 10, we asked whether OTUB1 could bind to UBC13 in the presence of UEV1a."
22367539
reach
"These data suggest that SET7-mediated methylation of OTUB1 attenuates OTUB1 binding to UBC13."
36822329
sparser
"Another DUB, OTUB1, directly binds and inhibits the E2 Ubc13 by a mechanism independent of its catalytic isopeptidase activity [ xref ]."
21549706
reach
"Binding of OTUB1 to UBC13 was measured by fluorescence anisotropy using fluorescently labeled UBC13, and equilibrium dissociation constants were calculated using SigmaPlot (SPSS)."
22367539
biogrid
No evidence text available
19615732
biogrid
No evidence text available
36822329
reach
"So, it is still enigmatic why K122 of OTUB1 methylated by SET7 could impair OTUB1 binding to UBC13."
36822329
sparser
"This interaction can be utilized for developing an RNF168 inhibitor by investigating OTUB1-UBC13 interaction, or the RNF168–UBC13 interaction interface inhibitor."
37760968
reach
"Furthermore, OTUB1 and Ubc13 interactions are mainly hydrophobic, as are OpsI-Ubc13 interactions."
23542009
reach
"Although OspI and OTUB1 interact with Ubc13 similarly, OspI inhibits Ubc13 through a different mechanism."
23542009
biogrid
No evidence text available
24071738
sparser
"Further analysis reveals that OTUB1 binds to the E2 UBC13 in vivo , which inhibits the extension of the K63-linked chain ( xref )."
32240951
sparser
"SETD7, a lysine monomethylase, directly interacts with ubiquitin thioesterase 1 (OTUB1) to catalyse OTUB1 methylation at Lys 122, disrupting the interaction between OTUB1 and the anti-ferroptosis protein ubiquitin conjugating enzyme E2 N (UBE2N/UBC13) in H1299 lung cancer cells xref ."
41233346
sparser
"In contrast to HERC2, OTUB1 binds to and inhibits UBC13 and thereby suppresses RNF168-dependent polyubiquitination [53] ."
21570976
sparser
"Cellular roles have been identified for the interaction of OTUB1 with UBE2N and members of the UBE2D family, but not for interactions with UBE2E E2 enzymes."
30282802
sparser
"During the double strand break response, OTUB1 binds to UBE2N and suppresses synthesis of Lys-63–linked polyubiquitin at DNA double strand breaks, thereby regulating the DNA damage response ( xref )."
30282802
reach
"In contrast to HERC2, OTUB1 binds to and inhibits UBC13 and thereby suppresses RNF168-dependent polyubiquitination [53] ."
21570976
sparser
"OTUB1 binding to Ubc13 interferes with the interactions of donor ubiquitin and TRAF6 with the E2 enzyme, leading to the inhibition of Lys63-linked polyubiquitin chain synthesis in DNA damage response xref ."
23633953
reach
"OTUB1 binding to Ubc13 interferes with the interactions of donor ubiquitin and TRAF6 with the E2 enzyme, leading to the inhibition of Lys63 linked polyubiquitin chain synthesis in DNA damage response XREF_BIBR."
23633953
reach
"Like TARF6 and CHIP, OTUB1 binds to Ubc13 through the alpha1 helix, L1 and L2 loops (XREF_FIG)."
23633953
sparser
"Like TARF6 and CHIP, OTUB1 binds to Ubc13 through the α1 helix, L1 and L2 loops ( xref )."
23633953
reach
"In the screen, UBC13 (UBE2N) emerged as a promising target of OTUB1 because it was coimmunoprecipitated with OTUB1 upon stimulation with TgPFN (Fig. 3a, b) and LPS (Fig. 3c, d), and a previous study reported the interaction between nuclear OTUB1 and UBC13 in the context of DNA double-strand breaks."
32024978
sparser
"27,28 OTUB1 interacts with Ubc13 through the H1 helix and S3–S4 and 3 10 -1–H2 loops, which are the same regions involved in OspI binding ( Fig. S7 )."
23542009
sparser
"Furthermore, OTUB1 and Ubc13 interactions are mainly hydrophobic, as are OpsI–Ubc13 interactions."
23542009
sparser
"Although OspI and OTUB1 interact with Ubc13 similarly, OspI inhibits Ubc13 through a different mechanism."
23542009
sparser
"In the screen, UBC13 (UBE2N) emerged as a promising target of OTUB1 because it was coimmunoprecipitated with OTUB1 upon stimulation with TgPFN (Fig.  xref ) and LPS (Fig.  xref ), and a previous study reported the interaction between nuclear OTUB1 and UBC13 in the context of DNA double-strand breaks. xref Functionally, UBC13 acts as an E2-conjugating enzyme in the NF-κB pathway."
32024978
reach
"The results presented in the present study provide evidence that the DUB OTUB1 critically supports canonical NF-κB activation in DCs and mediates DC-dependent protection in infectious disease, but augments immunopathology upon LPS challenge.Mechanistically, we identified that UBC13 interacts with OTUB1 upon TgPFN and LPS stimulation, extending the results of a previous study showing that, in the cell nucleus, OTUB1 binds UBC13 in response to DNA double-strand breaks."
32024978
reach
"Accordingly, OTUB1 binds to and inhibits UBC13 (UBE2N), the cognate E2 enzyme for RNF168."
26148240
sparser
"The OTUB1 protein interacts directly with the E2 ubiquitin-conjugating protein UBC13 and prevents ubiquitin transfer, thereby inhibiting double-strand-break-induced chromatin ubiquitination xref , xref ."
28776570
reach
"RNF8-Ubc13 interaction is positively regulated by the giant E3 ligase HERC2 [XREF_BIBR], and negatively regulated by the DUB OTUB1, which binds to Ubc13, thereby limiting access of RING domain E3 ligases [XREF_BIBR]."
21621538
sparser
"SET7-mediated methylation of OTUB1 attenuates OTUB1 binding to UBC13."
36822329
reach
"OTUB1 binds to UBC13 (UBE2N), an E2 ubiquitin-conjugating enzyme for RNF168, and restricts its interaction with RNF168, suppressing the DSB responses by inhibiting RNF168-induced polyubiquitylation independently of its catalytic activity [64]."
35897775
reach
"By binding to OTUB1, UBC13-Ub could neither transfer ubiquitin nor bind to E3 ligase."
28031783
sparser
"The deubiquitylating enzyme (DUB) OTUB1 binds UBC13, the ubiquitin-conjugating enzyme for RNF168, and inhibits polyubiquitylation independently of its catalytic activity ( xref )."
27083998
sparser
"Ectopically expressed SET7 inhibited the interaction between reconstituted OTUB1 with endogenous UBC13 in OTUB1 −/− H1299 cells ( xref A )."
36822329
sparser
"Furthermore, in OTUB1 −/− H1299 cells, reconstitution of WT OTUB1 bound to more endogenous UBC13 than reconstitution of the methylation-mimic mutant of OTUB1 (K122F) ( xref B )."
36822329
sparser
"The K d for binding of UBE2N to OTUB1 was 8.1 μM, which is consistent with previous studies that measured a K d of 7.04 μM using fluorescence polarization xref and K d of 8.9 μM measured by surface plasmon resonance using a GST-OTUB1 fusion xref ."
32049508
sparser
"In addition, coimmunoprecipitation assay showed that endogenous Ubc13 bound to more endogenous Otub1 in Set7 -deficient mouse embryo fibroblast (MEF) cells ( Set7 −/− ) than in Set7 -intact MEF cells ( Set7 +/+ ) ( xref C )."
36822329
biogrid
No evidence text available
26752685
sparser
"These data suggest that SET7-mediated methylation of OTUB1 attenuates OTUB1 binding to UBC13."
36822329
sparser
"Mechanistically, we identified that UBC13 interacts with OTUB1 upon TgPFN and LPS stimulation, extending the results of a previous study showing that, in the cell nucleus, OTUB1 binds UBC13 in response to DNA double-strand breaks. xref With respect to TLR signaling, UBC13 is a key molecule that bolsters MyD88-mediated NF-κB activity by cooperating with the E3 ligases Pellino and TRAF6."
32024978
sparser
"Moreover, SETD7, a lysine monomethylase, directly interacts with OTUB1 to catalyze the methylation of OTUB1 at Lys 122, disrupting the interaction between OTUB1 and the anti -ferroptosis protein ubiquitin conjugating enzyme E2 N (UBE2N/UBC13) in H1299 lung cancer cells [ xref ]."
38955112
reach
"The binding of Ubc13 with OTUB1 and its variant was performed by the Octet RED Instrument (FortéBIO) in a 96-well plate format."
38663827
biogrid
No evidence text available
25872870
sparser
"Since OTUB1 possesses a noncanonical function independently of its DUB activity by binding to and inhibiting the E2 ubiquitin-conjugation enzymes, such as UBC13 ( xref , xref , xref ), SET7-mediated methylation of OTUB1 attenuates OTUB1 binding to UBC13."
36822329
biogrid
No evidence text available
30718280
sparser
"The binding of free ubiquitin to the distal ubiquitin binding site of OTUB1 triggers conformational changes in the OTU domain and the formation of a ubiquitin-binding helix in the N terminus of OTUB1, promoting tight interaction between OTUB1 and ubiquitin-charged UBC13 [ xref ]."
26983989
sparser
"Finally, OTUB1 depletion mitigates the DSB repair defect associated with defective ATM signalling, indicating that pharmacological targeting of the OTUB1-UBC13 interaction might enhance the DNA damage response."
20725033
reach
"Previous studies have shown that, in cells, OTUB1 binds to E2-conjugating enzymes of the UBE2D (UBCH5) and UBE2E families, as well as to UBE2N (UBC13)."
30282802
reach
"Furthermore, the atomic level information of the interaction between human OTUB1 and UBC13 has not been reported."
22679021
sparser
"The deubiquitinase OTUB1 interacts with the lysine demethylase SET7 to affect the binding activity of OTUB1 to UBC13."
40959280
reach
"In vitro experiments show that OTUB1 binds directly to the charged E2 Ubc13, without a requirement for its cofactor UEV1a, and inhibits isopeptide bond formation between the donor ubiquitin on Ubc13 a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
22743550
sparser
"It appears that the N-terminus and the OUT domain are critical for OTUB1 binding to and inhibition of UBC13."
36822329
biogrid
No evidence text available
32049508
sparser
"Here, we found that K122 of OTUB1 methylated by SET7 could affect OTUB1 binding to UBC13 obviously."
36822329
sparser
"So, it is still enigmatic why K122 of OTUB1 methylated by SET7 could impair OTUB1 binding to UBC13."
36822329
biogrid
No evidence text available
22679021
biogrid
No evidence text available
22679021
sparser
"Distal site substitutions F193W, F193R and H217W disrupted the ability of OTUB1 to inhibit polyubiquitination by UBC13/UEV1a ( xref ) without affecting binding of OTUB1 to UBC13 ( xref )."
22367539
biogrid
No evidence text available
27173435
reach
"Since OTUB1 possesses a noncanonical function independently of its DUB activity by binding to and inhibiting the E2 ubiquitin-conjugation enzymes, such as UBC13 (4, 5, 6), SET7-mediated methylation of OTUB1 attenuates OTUB1 binding to UBC13."
36822329
reach
"Here, we found that K122 of OTUB1 methylated by SET7 could affect OTUB1 binding to UBC13 obviously."
36822329
biogrid
No evidence text available
22679021