Gene Symbol: UBE2D2
Description: ubiquitin conjugating enzyme E2 D2
Alias: E2(17)KB2, PUBC1, UBC4, UBC4/5, UBCH4, UBCH5B, ubiquitin-conjugating enzyme E2 D2, (E3-independent) E2 ubiquitin-conjugating enzyme D2, E2 ubiquitin-conjugating enzyme D2, p53-regulated ubiquitin-conjugating enzyme 1, ubiquitin carrier protein D2, ubiquitin conjugating enzyme E2D 2, ubiquitin-conjugating enzyme E2-17 kDa 2, ubiquitin-conjugating enzyme E2D 2 (homologous to yeast UBC4/5), ubiquitin-protein ligase D2
Species: human
Products:     UBE2D2

Top Publications

  1. Sheng Y, Hong J, Doherty R, Srikumar T, Shloush J, Avvakumov G, et al. A human ubiquitin conjugating enzyme (E2)-HECT E3 ligase structure-function screen. Mol Cell Proteomics. 2012;11:329-41 pubmed publisher
    ..Our data set represents the first comprehensive analysis of E2-HECT E3 interactions, and thus provides a framework for better understanding the molecular mechanisms of ubiquitylation. ..
  2. Ryan P, Sivadasan Nair N, Nau M, Nicholas S, Lipkowitz S. The N terminus of Cbl-c regulates ubiquitin ligase activity by modulating affinity for the ubiquitin-conjugating enzyme. J Biol Chem. 2010;285:23687-98 pubmed publisher
    ..of Tyr-341 or the Y341E mutation leads to a decrease in affinity for the ubiquitin-conjugating enzyme (E2), UbcH5b. The decreased affinity of the Y341E mutant Cbl-c for UbcH5b results in a more rapid turnover of bound UbcH5b ..
  3. Wu H, Pomeroy S, Ferreira M, Teider N, Mariani J, Nakayama K, et al. UBE4B promotes Hdm2-mediated degradation of the tumor suppressor p53. Nat Med. 2011;17:347-55 pubmed publisher
    ..Our data indicate that amplification and overexpression of UBE4B represent previously undescribed molecular mechanisms of inactivation of p53 in brain tumors. ..
  4. Dornan D, Wertz I, Shimizu H, Arnott D, Frantz G, Dowd P, et al. The ubiquitin ligase COP1 is a critical negative regulator of p53. Nature. 2004;429:86-92 pubmed
    ..Overall, these results indicate that COP1 is a critical negative regulator of p53 and represents a new pathway for maintaining p53 at low levels in unstressed cells. ..
  5. Demand J, Alberti S, Patterson C, Hohfeld J. Cooperation of a ubiquitin domain protein and an E3 ubiquitin ligase during chaperone/proteasome coupling. Curr Biol. 2001;11:1569-77 pubmed
    ..The chaperone cofactors thus act as key regulators to influence protein quality control. ..
  6. Uldrijan S, Pannekoek W, Vousden K. An essential function of the extreme C-terminus of MDM2 can be provided by MDMX. EMBO J. 2007;26:102-12 pubmed
    ..Interestingly, the E3 activity of C-terminal point mutants of MDM2 can also be supported by interaction with wild-type MDMX, suggesting that MDMX can directly contribute to E3 function. ..
  7. Fang S, Jensen J, Ludwig R, Vousden K, Weissman A. Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53. J Biol Chem. 2000;275:8945-51 pubmed
    ..However, this RING was ineffective in ubiquitination and proteasomal targeting of p53, suggesting that there may be specificity at the level of the RING in the recognition of heterologous substrates. ..
  8. Mace P, Linke K, Feltham R, Schumacher F, Smith C, Vaux D, et al. Structures of the cIAP2 RING domain reveal conformational changes associated with ubiquitin-conjugating enzyme (E2) recruitment. J Biol Chem. 2008;283:31633-40 pubmed publisher
    ..crystal structures of the cIAP2 RING domain homodimer alone, and bound to the ubiquitin-conjugating (E2) enzyme UbcH5b. These structures show that small changes in the RING domain accompany E2 binding...
  9. Watkins G, Wang N, Mazalouskas M, Gomez R, Guthrie C, Kraemer B, et al. Monoubiquitination promotes calpain cleavage of the protein phosphatase 2A (PP2A) regulatory subunit ?4, altering PP2A stability and microtubule-associated protein phosphorylation. J Biol Chem. 2012;287:24207-15 pubmed publisher
    ..These findings indicate that regulated inter-domain cleavage controls the dual functions of ?4, and dysregulation of ?4 cleavage may contribute to Opitz syndrome and Alzheimer disease. ..

More Information


  1. Dou H, Buetow L, Hock A, Sibbet G, Vousden K, Huang D. Structural basis for autoinhibition and phosphorylation-dependent activation of c-Cbl. Nat Struct Mol Biol. 2012;19:184-92 pubmed publisher
    ..This activation is required for RTK ubiquitination. Our results present a mechanism for regulation of c-Cbl's activity by autoinhibition and phosphorylation-induced activation. ..
  2. Sheng Y, Laister R, Lemak A, Wu B, Tai E, Duan S, et al. Molecular basis of Pirh2-mediated p53 ubiquitylation. Nat Struct Mol Biol. 2008;15:1334-42 pubmed publisher
    ..As a result, Pirh2 preferentially ubiquitylates the tetrameric form of p53 in vitro and in vivo, suggesting that Pirh2 regulates protein turnover of the transcriptionally active form of p53. ..
  3. Wu P, Hanlon M, Eddins M, Tsui C, Rogers R, Jensen J, et al. A conserved catalytic residue in the ubiquitin-conjugating enzyme family. EMBO J. 2003;22:5241-50 pubmed
    ..We propose that the conserved asparagine side chain stabilizes the oxyanion intermediate formed during lysine attack. The E2 asparagine is the first non-covalent catalytic group to be proposed in any Ub conjugation factor. ..
  4. Nakatani Y, Kleffmann T, Linke K, Condon S, Hinds M, Day C. Regulation of ubiquitin transfer by XIAP, a dimeric RING E3 ligase. Biochem J. 2013;450:629-38 pubmed publisher
    ..RING dimerization is a critical activating step for the cIAP proteins; however, our analysis shows that the RING domain of XIAP forms a stable dimer and its E3 ligase activity does not require an activation step. ..
  5. Isasa M, Katz E, Kim W, Yugo V, González S, Kirkpatrick D, et al. Monoubiquitination of RPN10 regulates substrate recruitment to the proteasome. Mol Cell. 2010;38:733-45 pubmed publisher
    ..Our results reveal an unanticipated link between monoubiquitination signal and regulation of proteasome function. ..
  6. Kamadurai H, Souphron J, Scott D, Duda D, Miller D, Stringer D, et al. Insights into ubiquitin transfer cascades from a structure of a UbcH5B approximately ubiquitin-HECT(NEDD4L) complex. Mol Cell. 2009;36:1095-102 pubmed publisher
    ..into this process, we determined the crystal structure of a complex between the HECT domain of NEDD4L and the E2 UbcH5B bearing a covalently linked Ub at its active site (UbcH5B approximately Ub)...
  7. Jensen J, Bates P, Yang M, Vierstra R, Weissman A. Identification of a family of closely related human ubiquitin conjugating enzymes. J Biol Chem. 1995;270:30408-14 pubmed
    ..Analysis of Southern blots suggests that there are likely to be other related members of this family. Both UbcH5B and UbcH5C form thiol ester adducts with ubiquitin, and have activities similar to UbcH5A and AtUBC8 in the ..
  8. Kirisako T, Kamei K, Murata S, Kato M, Fukumoto H, Kanie M, et al. A ubiquitin ligase complex assembles linear polyubiquitin chains. EMBO J. 2006;25:4877-87 pubmed
    ..Moreover, the complex regulates the stability of Ub-GFP (a GFP fusion protein with an N-terminal ubiquitin). The linear polyubiquitin chain generated post-translationally may function as a new modulator of proteins. ..
  9. Shloush J, Vlassov J, Engson I, Duan S, Saridakis V, Dhe Paganon S, et al. Structural and functional comparison of the RING domains of two p53 E3 ligases, Mdm2 and Pirh2. J Biol Chem. 2011;286:4796-808 pubmed publisher
    ..This comprehensive analysis of the Pirh2 and Mdm2 RING domains provides structural and mechanistic insight into p53 regulation by its E3 ligases. ..
  10. Soss S, Yue Y, Dhe Paganon S, Chazin W. E2 conjugating enzyme selectivity and requirements for function of the E3 ubiquitin ligase CHIP. J Biol Chem. 2011;286:21277-86 pubmed publisher
    ..These data support the proposal that the E2 SPA motif provides specificity for binding to CHIP, whereas activation of the E2?Ub conjugate is derived from other molecular determinants. ..
  11. Chaugule V, Burchell L, Barber K, Sidhu A, Leslie S, Shaw G, et al. Autoregulation of Parkin activity through its ubiquitin-like domain. EMBO J. 2011;30:2853-67 pubmed publisher
    ..Our observations provide important molecular insights into the underlying basis of Parkinson's disease, and in the regulation of RBR E3-ligase activity. ..
  12. David Y, Ternette N, Edelmann M, Ziv T, Gayer B, Sertchook R, et al. E3 ligases determine ubiquitination site and conjugate type by enforcing specificity on E2 enzymes. J Biol Chem. 2011;286:44104-15 pubmed publisher
    ..Based on several model systems, we propose that although interaction with an E2 is sufficient to promote substrate ubiquitination the E3 molds the reaction into a specific, physiologically relevant protein modification. ..
  13. Kobashigawa Y, Tomitaka A, Kumeta H, Noda N, Yamaguchi M, Inagaki F. Autoinhibition and phosphorylation-induced activation mechanisms of human cancer and autoimmune disease-related E3 protein Cbl-b. Proc Natl Acad Sci U S A. 2011;108:20579-84 pubmed publisher
    ..Moreover, the phosphate group of pY363 is located in the vicinity of the interaction surface with UbcH5B to increase affinity by reducing their electrostatic repulsion...
  14. Joazeiro C, Wing S, Huang H, Leverson J, Hunter T, Liu Y. The tyrosine kinase negative regulator c-Cbl as a RING-type, E2-dependent ubiquitin-protein ligase. Science. 1999;286:309-12 pubmed
    ..These results reveal an SH2-containing protein that functions as a ubiquitin-protein ligase and thus provide a distinct mechanism for substrate targeting in the ubiquitin system. ..
  15. Hatakeyama S, Matsumoto M, Kamura T, Murayama M, Chui D, Planel E, et al. U-box protein carboxyl terminus of Hsc70-interacting protein (CHIP) mediates poly-ubiquitylation preferentially on four-repeat Tau and is involved in neurodegeneration of tauopathy. J Neurochem. 2004;91:299-307 pubmed
    ..Thus, CHIP is a ubiquitin ligase for four-repeat tau and maintains neuronal survival by regulating the quality control of tau in neurons. ..
  16. Saville M, Sparks A, Xirodimas D, Wardrop J, Stevenson L, Bourdon J, et al. Regulation of p53 by the ubiquitin-conjugating enzymes UbcH5B/C in vivo. J Biol Chem. 2004;279:42169-81 pubmed
    ..The same E2s also support Mdm2 auto-ubiquitination. Small interfering RNA-mediated knockdown of UbcH5B/C causes accumulation of Mdm2 and p53 in unstressed cells...
  17. Kumar S, Kao W, Howley P. Physical interaction between specific E2 and Hect E3 enzymes determines functional cooperativity. J Biol Chem. 1997;272:13548-54 pubmed
  18. Rodriguez M, Desterro J, Lain S, Midgley C, Lane D, Hay R. SUMO-1 modification activates the transcriptional response of p53. EMBO J. 1999;18:6455-61 pubmed
    ..The SUMO-1 modification pathway therefore acts as a potential regulator of the p53 response and may represent a novel target for the development of therapeutically useful modulators of the p53 response. ..
  19. Dou H, Buetow L, Sibbet G, Cameron K, Huang D. BIRC7-E2 ubiquitin conjugate structure reveals the mechanism of ubiquitin transfer by a RING dimer. Nat Struct Mol Biol. 2012;19:876-83 pubmed publisher
    ..Here we report the structure of the human dimeric RING domain from BIRC7 in complex with the E2 UbcH5B covalently linked to Ub (UbcH5B?Ub)...
  20. Geisler S, Vollmer S, Golombek S, Kahle P. The ubiquitin-conjugating enzymes UBE2N, UBE2L3 and UBE2D2/3 are essential for Parkin-dependent mitophagy. J Cell Sci. 2014;127:3280-93 pubmed publisher
    ..Knockdown of the E2 enzymes UBE2N, UBE2L3 or UBE2D2 and UBE2D3 (UBE2D2/3) significantly reduced autophagic clearance of depolarized mitochondria...
  21. Hoeller D, Hecker C, Wagner S, Rogov V, Dötsch V, Dikic I. E3-independent monoubiquitination of ubiquitin-binding proteins. Mol Cell. 2007;26:891-8 pubmed
    ..This modification is mechanistically and functionally distinct from E3-mediated and growth factor-dependent monoubiquitination. ..
  22. Li W, Bengtson M, Ulbrich A, Matsuda A, Reddy V, Orth A, et al. Genome-wide and functional annotation of human E3 ubiquitin ligases identifies MULAN, a mitochondrial E3 that regulates the organelle's dynamics and signaling. PLoS ONE. 2008;3:e1487 pubmed publisher
    ..These findings suggest the existence of a new, Ub-mediated mechanism responsible for integration of mitochondria into the cellular environment. ..
  23. Xia Y, Pao G, Chen H, Verma I, Hunter T. Enhancement of BRCA1 E3 ubiquitin ligase activity through direct interaction with the BARD1 protein. J Biol Chem. 2003;278:5255-63 pubmed
    ..that its RING finger domain can autoubiquitylate and monoubiquitylate histone H2A when supplied with Ub, E1, and UBC4 (E2)...
  24. Feltham R, Bettjeman B, Budhidarmo R, Mace P, Shirley S, Condon S, et al. Smac mimetics activate the E3 ligase activity of cIAP1 protein by promoting RING domain dimerization. J Biol Chem. 2011;286:17015-28 pubmed publisher
    ..These results explain how Smac mimetics promote rapid destruction of cIAP1 and suggest mechanisms for activating cIAP1 in other pathways. ..
  25. Dou H, Buetow L, Sibbet G, Cameron K, Huang D. Essentiality of a non-RING element in priming donor ubiquitin for catalysis by a monomeric E3. Nat Struct Mol Biol. 2013;20:982-986 pubmed publisher
    ..Hence, interactions outside the canonical RING domain are crucial for optimizing Ub transfer in both monomeric and dimeric RING E3s. We propose that an additional non-RING Ub-priming element may be a common RING E3 feature. ..
  26. Imai Y, Soda M, Hatakeyama S, Akagi T, Hashikawa T, Nakayama K, et al. CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity. Mol Cell. 2002;10:55-67 pubmed
    ..Furthermore, CHIP enhanced the ability of Parkin to inhibit cell death induced by Pael-R. Taken together, these results indicate that CHIP is a mammalian E4-like molecule that positively regulates Parkin E3 activity. ..
  27. Shimura H, Schwartz D, Gygi S, Kosik K. CHIP-Hsc70 complex ubiquitinates phosphorylated tau and enhances cell survival. J Biol Chem. 2004;279:4869-76 pubmed
    ..Ub) by the E3 Ub ligase CHIP (carboxyl terminus of the Hsc70-interacting protein) and the E2 conjugating enzyme UbcH5B. Other E3 Ub ligases including parkin and Cbl failed to ubiquitinate phosphorylated tau...
  28. Leverson J, Joazeiro C, Page A, Huang H, Hieter P, Hunter T. The APC11 RING-H2 finger mediates E2-dependent ubiquitination. Mol Biol Cell. 2000;11:2315-25 pubmed
    ..yeast cell viability, Using purified, recombinant proteins we showed that Apc11p interacted directly with the Ubc4 ubiquitin conjugating enzyme (E2)...
  29. Kigoshi Y, Tsuruta F, Chiba T. Ubiquitin ligase activity of Cul3-KLHL7 protein is attenuated by autosomal dominant retinitis pigmentosa causative mutation. J Biol Chem. 2011;286:33613-21 pubmed publisher
  30. Wu H, Leng R. MDM2 mediates p73 ubiquitination: a new molecular mechanism for suppression of p73 function. Oncotarget. 2015;6:21479-92 pubmed
    ..Furthermore, the data suggest a link between p73 ubiquitination/MDM2 E3 ligase activity and p73 biological functions. ..
  31. Duan S, Yao Z, Hou D, Wu Z, Zhu W, Wu M. Phosphorylation of Pirh2 by calmodulin-dependent kinase II impairs its ability to ubiquitinate p53. EMBO J. 2007;26:3062-74 pubmed
    ..Together, our data suggest that phosphorylation of Pirh2 may act as a fine-tuning to maintain the balance of p53-Pirh2 autoregulatory feedback loop, which facilitates the tight regulation of p53 stability and tumor suppression. ..
  32. Durcan T, Kontogiannea M, Thorarinsdottir T, Fallon L, WILLIAMS A, Djarmati A, et al. The Machado-Joseph disease-associated mutant form of ataxin-3 regulates parkin ubiquitination and stability. Hum Mol Genet. 2011;20:141-54 pubmed publisher
  33. Choi H, Gully C, Su C, Velazquez Torres G, Chou P, Tseng C, et al. COP9 signalosome subunit 6 stabilizes COP1, which functions as an E3 ubiquitin ligase for 14-3-3?. Oncogene. 2011;30:4791-801 pubmed publisher
    ..These data suggest that the CSN6-COP1 axis is involved in 14-3-3? degradation, and that deregulation of this axis will promote cell growth and tumorigenicity. ..
  34. Schweiger S, Dorn S, Fuchs M, Köhler A, Matthes F, Müller E, et al. The E3 ubiquitin ligase MID1 catalyzes ubiquitination and cleavage of Fu. J Biol Chem. 2014;289:31805-17 pubmed publisher
    ..Our data suggest that Fu ubiquitination and cleavage is one of the key elements connecting the MID1-PP2A protein complex with GLI3 activity control. ..
  35. Wright J, Mace P, Day C. Secondary ubiquitin-RING docking enhances Arkadia and Ark2C E3 ligase activity. Nat Struct Mol Biol. 2016;23:45-52 pubmed publisher
    ..This study also suggests how substrates that have been monoubiquitinated could be favored for further ubiquitination. ..
  36. Chesarino N, McMichael T, Yount J. E3 Ubiquitin Ligase NEDD4 Promotes Influenza Virus Infection by Decreasing Levels of the Antiviral Protein IFITM3. PLoS Pathog. 2015;11:e1005095 pubmed publisher
    ..Overall, this work identifies the enzyme NEDD4 as a new therapeutic target for the prevention of influenza virus infections, and introduces a new paradigm for up-regulating cellular levels of IFITM3 independently of IFN or infection. ..
  37. Jin Y, Zeng S, Lee H, Lu H. MDM2 mediates p300/CREB-binding protein-associated factor ubiquitination and degradation. J Biol Chem. 2004;279:20035-43 pubmed
    ..Furthermore, MDM2 reduced the half-life of PCAF by 50%. These results demonstrate that MDM2 regulates the stability of PCAF by ubiquitinating and degrading this protein. ..
  38. Raheja R, Liu Y, Hukkelhoven E, Yeh N, Koff A. The ability of TRIM3 to induce growth arrest depends on RING-dependent E3 ligase activity. Biochem J. 2014;458:537-45 pubmed publisher
    ..Thus the ability of TRIM3 to suppress growth is associated with its ability to ubiquitinate proteins. ..
  39. Peng Z, Shi T, Ma D. RNF122: a novel ubiquitin ligase associated with calcium-modulating cyclophilin ligand. BMC Cell Biol. 2010;11:41 pubmed publisher
    ..RNF122 promotes its own degradation in a RING finger-and proteasome-dependent manner. RNF122 interacts with CAML, and its E3 ubiquitin ligase activity was noted to be dependent on the RING finger domain. ..
  40. Sugeno N, Hasegawa T, Tanaka N, Fukuda M, Wakabayashi K, Oshima R, et al. Lys-63-linked ubiquitination by E3 ubiquitin ligase Nedd4-1 facilitates endosomal sequestration of internalized ?-synuclein. J Biol Chem. 2014;289:18137-51 pubmed publisher
    ..Together, these findings demonstrate that Nedd4-1-linked Lys-63 ubiquitination specifies the fate of extrinsic and de novo synthesized aS by facilitating their targeting to endosomes. ..
  41. Du H, Wu K, Didoronkute A, Levy M, Todi N, Shchelokova A, et al. MID1 catalyzes the ubiquitination of protein phosphatase 2A and mutations within its Bbox1 domain disrupt polyubiquitination of alpha4 but not of PP2Ac. PLoS ONE. 2014;9:e107428 pubmed publisher
  42. Rott R, Szargel R, Haskin J, Bandopadhyay R, Lees A, Shani V, et al. α-Synuclein fate is determined by USP9X-regulated monoubiquitination. Proc Natl Acad Sci U S A. 2011;108:18666-71 pubmed publisher
    ..Our data indicate that monoubiquitination is a key determinant of α-synuclein fate. ..
  43. Wright F, Lu J, Sliter D, Dupré N, Rouleau G, Wojcikiewicz R. A Point Mutation in the Ubiquitin Ligase RNF170 That Causes Autosomal Dominant Sensory Ataxia Destabilizes the Protein and Impairs Inositol 1,4,5-Trisphosphate Receptor-mediated Ca2+ Signaling. J Biol Chem. 2015;290:13948-57 pubmed publisher
    ..Rather, the defect likely reflects abnormal ubiquitination of other substrates, or adaptation to the chronic reduction in RNF170 levels. ..
  44. Yang Y, Ludwig R, Jensen J, Pierre S, Medaglia M, Davydov I, et al. Small molecule inhibitors of HDM2 ubiquitin ligase activity stabilize and activate p53 in cells. Cancer Cell. 2005;7:547-59 pubmed
    ..In cells, the compounds allow the stabilization of p53 and HDM2 and activation of p53-dependent transcription and apoptosis, although other p53-independent toxicity was also observed. ..
  45. Sun M, Cai J, Anderson R, Sun Y. Type I ? Phosphatidylinositol Phosphate 5-Kinase i5 Controls the Ubiquitination and Degradation of the Tumor Suppressor Mitogen-inducible Gene 6. J Biol Chem. 2016;291:21461-21473 pubmed
    ..Thus, loss of NEDD4-1 can rescue Mig6 expression in PIPKI?i5 knockdown cells. In this way, PIPKI?i5, NEDD4-1, and Mig6 form a novel molecular nexus that controls EGFR activation and downstream signaling. ..
  46. Plafker K, Nguyen L, Barneche M, Mirza S, Crawford D, Plafker S. The ubiquitin-conjugating enzyme UbcM2 can regulate the stability and activity of the antioxidant transcription factor Nrf2. J Biol Chem. 2010;285:23064-74 pubmed publisher
    ..This work implicates UbcM2 in the restoration of redox homeostasis following oxidative stress. ..
  47. Yamauchi K, Wada K, Tanji K, Tanaka M, Kamitani T. Ubiquitination of E3 ubiquitin ligase TRIM5 alpha and its potential role. FEBS J. 2008;275:1540-55 pubmed publisher
    ..ligase both in vitro and in vivo and ubiquitinates itself in cooperation with the E2 ubiquitin-conjugating enzyme UbcH5B. In addition to the self-ubiquitination, we show that TRIM5alpha is ubiquitinated by another E3 ubiquitin ligase, ..
  48. Hatakeyama S, Jensen J, Weissman A. Subcellular localization and ubiquitin-conjugating enzyme (E2) interactions of mammalian HECT family ubiquitin protein ligases. J Biol Chem. 1997;272:15085-92 pubmed
    ..that is 40% identical between mE6-AP and Nedd-4 as a binding site for the C-terminal portion of an E2 enzyme (UbcH5B)...
  49. Chen Z, Barbi J, Bu S, Yang H, Li Z, Gao Y, et al. The ubiquitin ligase Stub1 negatively modulates regulatory T cell suppressive activity by promoting degradation of the transcription factor Foxp3. Immunity. 2013;39:272-85 pubmed publisher
  50. Suzuki S, Suzuki T, Mimuro H, Mizushima T, Sasakawa C. Shigella hijacks the glomulin-cIAPs-inflammasome axis to promote inflammation. EMBO Rep. 2018;19:89-101 pubmed publisher
    ..These findings suggest that GLMN is a negative regulator of cIAP-mediated inflammasome activation, and highlight a unique Shigella stratagem to kill macrophages, promoting severe inflammation. ..
  51. Takeyama K, Aguiar R, Gu L, He C, Freeman G, Kutok J, et al. The BAL-binding protein BBAP and related Deltex family members exhibit ubiquitin-protein isopeptide ligase activity. J Biol Chem. 2003;278:21930-7 pubmed
    ..Consistent with this idea, BBAP and DTX1 associate via their unique N termini, resulting in enhanced self-ubiquitination. ..
  52. Ahn J, Novince Z, Concel J, Byeon C, Makhov A, Byeon I, et al. The Cullin-RING E3 ubiquitin ligase CRL4-DCAF1 complex dimerizes via a short helical region in DCAF1. Biochemistry. 2011;50:1359-67 pubmed publisher
  53. Wada K, Niida M, Tanaka M, Kamitani T. Ro52-mediated monoubiquitination of IKK{beta} down-regulates NF-{kappa}B signalling. J Biochem. 2009;146:821-32 pubmed publisher
    ..a phosphomimetic mutant IKKbeta to conjugate monoubiquitin in cooperation with an E2-ubiquitin-conjugating enzyme UbcH5B. These results suggest that the Tax-induced phosphorylation of IKKbeta causes an interaction with Ro52 for the ..
  54. Ryo A, Suizu F, Yoshida Y, Perrem K, Liou Y, Wulf G, et al. Regulation of NF-kappaB signaling by Pin1-dependent prolyl isomerization and ubiquitin-mediated proteolysis of p65/RelA. Mol Cell. 2003;12:1413-26 pubmed
    ..These findings uncover two important mechanisms of regulating NF-kappaB signaling and offer new insight into the pathogenesis and treatment of some human diseases such as cancers. ..
  55. Winkler G, Albert T, Dominguez C, Legtenberg Y, Boelens R, Timmers H. An altered-specificity ubiquitin-conjugating enzyme/ubiquitin-protein ligase pair. J Mol Biol. 2004;337:157-65 pubmed
    ..Here we show that binding of the CNOT4 RING finger to the ubiquitin-conjugating enzyme (E2) UbcH5B is highly selective...
  56. Streich F, Ronchi V, Connick J, Haas A. Tripartite motif ligases catalyze polyubiquitin chain formation through a cooperative allosteric mechanism. J Biol Chem. 2013;288:8209-21 pubmed publisher
    ..These results represent the first detailed mechanistic study of TRIM ligase activity and provide a functional context for oligomerization observed in the superfamily. ..
  57. Kamadurai H, Qiu Y, Deng A, Harrison J, MacDonald C, Actis M, et al. Mechanism of ubiquitin ligation and lysine prioritization by a HECT E3. elife. 2013;2:e00828 pubmed publisher
    ..DOI:http://dx.doi.org/10.7554/eLife.00828.001. ..
  58. Ferretti L, Himmels S, Trenner A, Walker C, von Aesch C, Eggenschwiler A, et al. Cullin3-KLHL15 ubiquitin ligase mediates CtIP protein turnover to fine-tune DNA-end resection. Nat Commun. 2016;7:12628 pubmed publisher
    ..Collectively, our findings underline the key importance and high complexity of CtIP modulation for genome integrity. ..
  59. Camp N, James R, Dawson D, Yan F, Davison J, Houck S, et al. Wilms tumor gene on X chromosome (WTX) inhibits degradation of NRF2 protein through competitive binding to KEAP1 protein. J Biol Chem. 2012;287:6539-50 pubmed publisher
    ..These results expand our understanding of the molecular mechanisms of WTX and reveal a novel regulatory mechanism governing the antioxidant response. ..
  60. Jang J. FIGC, a novel FGF-induced ubiquitin-protein ligase in gastric cancers. FEBS Lett. 2004;578:21-5 pubmed
    ..Our data indicate that FIGC upregulation in response to bFGF in gastric cancer might be implicated in carcinogenesis through dysregulation of growth modulator. ..
  61. Dornan D, Shimizu H, Mah A, Dudhela T, Eby M, O Rourke K, et al. ATM engages autodegradation of the E3 ubiquitin ligase COP1 after DNA damage. Science. 2006;313:1122-6 pubmed
    ..Furthermore, phosphorylation of COP1 on Ser(387) was required to permit p53 to become stabilized and to exert its tumor suppressor properties in response to DNA damage. ..
  62. Sakane A, Hatakeyama S, Sasaki T. Involvement of Rabring7 in EGF receptor degradation as an E3 ligase. Biochem Biophys Res Commun. 2007;357:1058-64 pubmed
    ..with recombinant E1 and E2 proteins that Rabring7 has E3 ligase activity and that it preferentially reacts with Ubc4 and Ubc5 as its E2 proteins...
  63. Hasanov E, Chen G, Chowdhury P, Weldon J, Ding Z, Jonasch E, et al. Ubiquitination and regulation of AURKA identifies a hypoxia-independent E3 ligase activity of VHL. Oncogene. 2017;36:3450-3463 pubmed publisher
    ..Together, these data identify VHL as an E3 ligase with important cellular functions under both normoxic and hypoxic conditions. ..
  64. Koh M, Darnay B, Powis G. Hypoxia-associated factor, a novel E3-ubiquitin ligase, binds and ubiquitinates hypoxia-inducible factor 1alpha, leading to its oxygen-independent degradation. Mol Cell Biol. 2008;28:7081-95 pubmed publisher
    ..Therefore, HAF is the key mediator of a new HIF-1alpha-specific degradation pathway that degrades HIF-1alpha through a new, oxygen-independent mechanism. ..
  65. Beck J, Maerki S, Posch M, Metzger T, Persaud A, Scheel H, et al. Ubiquitylation-dependent localization of PLK1 in mitosis. Nat Cell Biol. 2013;15:430-9 pubmed publisher
    ..Our data suggest that CUL3-KLHL22-mediated ubiquitylation signals degradation-independent removal of PLK1 from kinetochores and SAC satisfaction, which are required for faithful mitosis. ..
  66. Benirschke R, Thompson J, Nominé Y, Wasielewski E, Juranic N, Macura S, et al. Molecular basis for the association of human E4B U box ubiquitin ligase with E2-conjugating enzymes UbcH5c and Ubc4. Structure. 2010;18:955-65 pubmed publisher
    ..X-ray crystallography and NMR spectroscopy, we determined the structures of E4B U box free and bound to UbcH5c and Ubc4 E2s...
  67. Matta Camacho E, Kozlov G, Ménade M, Gehring K. Structure of the HECT C-lobe of the UBR5 E3 ubiquitin ligase. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012;68:1158-63 pubmed publisher
    ..This protruding loop is likely to contribute to specificity towards the E2 ubiquitin-conjugating enzyme UBCH4, which is an important functional partner of UBR5...
  68. Nomura K, Klejnot M, Kowalczyk D, Hock A, Sibbet G, Vousden K, et al. Structural analysis of MDM2 RING separates degradation from regulation of p53 transcription activity. Nat Struct Mol Biol. 2017;24:578-587 pubmed publisher
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