FunctionUbiquitin conjugating enzyme (Ubc) or E2 enzyme catalyzes the second step in the ubiquitination of a protein tagged to be degraded by the proteasome. Ubiquitin activating enzyme (E1) and ATP produce a C-terminal acyl adenylated ubiquitin molecule which binds to ubiquitin conjugating enzyme (E2) (Ubc) cysteine[1]. The Ubc then binds to ubiquitin ligase (E3) via a conserved binding region. E3 catalyzes the transfer of ubiquitin from the Ubc-ubiquitin complex to a lysine residue of the target protein. Ubc13 makes a catalytically active heterodimer with MMS2[2].
- UBC2 is required for silencing in yeast[3].
- UBC4 UBC5 mediate selective degradation of short-lived and abnormal proteins[4].
- UBC6 and UBC J2 participate in ER-associated protein degradation[5].
- UBC7 or UBC13 is key in the process of tagging target proteins with Lys63-linked polyubiquitin[6].
For more details on Ubc13 see UBC13 MMS2.
- UBC8 is interferon-inducible[7].
- UBC9 or SUMO conjugating enzyme Ubc9 is required for sumoylation[8].
For more details on Ubc9 see SUMO conjugating enzyme Ubc9.
- UBC16 conjugates ubiquitin to its N-terminus and to that of the small ubiquitin-like modifier SUMO[9].
- UBC D2,D3,Q1 functions in the ubiquitination of the tumor suppressor p53[10].
- UBC G2 functions in identification and degradation of misfolded proteins in the endoplasmic reticulum.
- UBC H acts on histones and cytoskeletal proteins[11].
- UBC K,R1 preferentially catalyses the formation of ubiquitin chain links to proteasome-bound proteins to Lys48[12].
- UBC S preferentially catalyses the formation of ubiquitin chain links of Lys11 to histones [13].
- UBC T acts in the Fanconi anemia pathway which is required for the efficient repair of damaged DNA[14].
- UBC Z is required for FAT10 conjugation (post-translational modification analogous to ubiquitination)[15].
- UBC Hip-2 mediates amyloid-β neurotoxicity[16].
- UBC Uev-1 is a variant of UBC which lacks its enzymatic activity[17].
DiseaseUBC13 is required for metastatic spread and lung colonizationin breast cancer[18].
Structural highlightsThe active site of Ubc contains a cysteine residue. The [19].
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3D Structures of ubiquitin conjugating enzyme3D Structures of ubiquitin conjugating enzyme
Updated on 04-January-2021
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- Ubiquitin conjugating enzyme
- 1jas – hUbc – human
- 2aak – AtUbc – Arabidopsis thaliana
- 2qcq, 1fzy – yUbc – yeast
- 1fxt – yUbc + ubiquitin
- 2e2c – Ubc – Spisula solidissima
- 1q34 – CeUbc – Caenorhabidis elegans
- 2fo3 – Ubc – Plasmodium vivax
- 2h2y – PfUbc – Plasmodium falciparum
- 6mj9, 5vor – Ubc – Naegleria fowleri
- Ubiquitin conjugating enzyme 1
- Ubiquitin conjugating enzyme 2
- 1ayz – yUbc
- 4r62 – yUbc + ubiquitin carboxyl extension protein 80
- 5aie – yUbc + NOT4
- 1z2u – CeUbc
- Ubiquitin conjugating enzyme 3 or Ubc3 or Cdc34
- Ubiquitin conjugating enzyme 4
- 1qcq – yUbc
- 5aie – yUbc + NOT4 RING domain
- 4ii2 – fyUbc (mutant) + E1 + ATP – fission yeast
- Ubiquitin conjugating enzyme 6
- 4jjq – hUbc + ubiquitin carboxyl terminal hydrolase
- Ubiquitin conjugating enzyme 7 or Ubc L3
- 2awf, 2cyx – hUbc
- 6xxu – hUbc - NMR
- 1c4z – hUbc + E3 HECT domain
- 1fbv – hUbc + E3 Cbl + ZAP-70 peptide
- 4jqu – hUbc + U7BR
- 3sqv – hUbc + secreted effector protein
- 3sy2 – hUbc + E3 Sopa
- 5udh – hUbc + ubiquitin + E3 ARIH1
- 4q5e, 4q5h – hUbc (mutant) + ubiquitin + OspG
- 6cp2 – hUbc (mutant) + UBB + SidC
- 6djw, 6djx, 6n13 – hUbc (mutant) + ubiquitin + PARKIN
- 5tte, 5udh – hUbc (mutant) + ubiquitin + ARIH1
- 5hpt – hUbc + ubiquitin + NEDD4-like E3 ubiquitin-protein
- 2ucz – yUbc
- Ubiquitin conjugating enzyme 8
- 1y6l, 1wzw, 1wzv – hUbc
- 2kjh – hUbc + ubiquitin
- 4x57 – AtUbc + membrane-anchord ubiquitin-fold protein
- Ubiquitin conjugating enzyme 9 see SUMO conjugating enzyme Ubc9
- Ubiquitin conjugating enzyme 10 or Ubc C
- 1i7k – hUbc (mutant)
- 4yii – hUbc + anaphase-promoting complex subunit 2
- Ubiquitin conjugating enzyme 12 (NEDD8 conjugating enzyme; Ubc F)
- 2edi – hUbc 2 UQ-CON domain - NMR
- 1y8x – hUbc + E1 NEDD8
- 1tt5 – hUbc + E1 Uba3, APPBP1 subunits
- 1y8x – hUbc + E1 NEDD8
- 2nvu – hUbc + E1 NEDD8 + NEDD8
- 3fn1 – hUbc + E1 NEDD8-activating enzyme
- 3tdu – hUbc + cullin-1 + Dcn1-like protein
- 4p5o – hUbc + cullin-1 + Dcn1-like protein + Rbx1 + NEDD8
- 4gao – hUbc + Dcn1-like protein
- 3tdi – hUbc + defective in cullin neddylation protein
- 3o2u – yUbc
- Ubiquitin conjugating enzyme 13 or Ubc N
- Ubiquitin conjugating enzyme 13 complexes
- 2c2v – hUbc + CHIP + Uev1a
- 3hct, 3hcu – hUbc + TNF receptor associated factor 6
- 4dhi, 4dhz – hUbc + OTUB1 + ubiquitin + ubiquitin aldehyde
- 4orh – hUbc/Mms2 + E3 Rnf8
- 3von – hUbc/Mms2 + OTUB1
- 1zgu – hMms2 + ubiquitin - NMR
- 5eya – hUbc + ubiquitin + TRIM25 ring domain
- 4tkp – hUbc + TRIM5 ring domain
- 2gmi – hUbc/Mms2 (mutant) + ubiquitin
- 4onl, 4onm, 4onn – hUbc + Mms2 (mutant)
- 4nr3, 4nrg, 4nri – hUbc (mutant) + Mms2
- 3von – hUbc + Otub1 + E2 variant
- 6d6i – hUbc + ubiquitin + E2 variant
- 4dhj – hUbc + ubiquitin + OTUB1
- 5vnz, 5vo0 – hUbc + ubiquitin + TraF6
- 6kl4, 7bxg, 6p5b, 6ulh, 6ump, 6ums – hUbc + ubiquitin + MavC
- 6kfp, 6kg6 – hUbc + ubiquitin-RPS27a + MavC
- 5ywr – hUbc + E3 ubiquitin-protein ligase ZANFR1
- 4whv, 6s53 – hUbc + ubiquitin + E3 ubiquitin-protein ligase
- 5ait, 5aiu – hUbc + ubiquitin + E3 ubiquitin-protein ligase RNF4
- 4orh – hUbc/Mms2 + E3 ubiquitin-protein ligase RN8
- 4ip3, 3w31 – hUbc + Orf169b
- 2oxq – Ubc + CHIP U-box - zebrafish
- 5ojw – yUbc + Mms2
- 6jky – yUbc + ubiquitin + MvcA
- 4dhi – CeUbc + OTUB1
- Ubiquitin conjugating enzyme 16 or Ubc W
- Ubiquitin conjugating enzyme A or Rad6
- Ubiquitin conjugating enzyme B
- Ubiquitin conjugating enzyme D1
- 2c4p – hUbc D1
- 2yho – hUbc D1 + E3 Mylip
- 5fer – hUbc D1 + ubiquitin carboxyl extension protein 80 + TRIM25 ring
- 4qpl – hUbc D1 + E3 ubiquitin-protein ligase RNF146
- 3ptf, 6d4p, 5tut – hUbc D1 + ubiquitin
- 4ap4 – hUbc D1 + E3 ubiquitin-protein ligase RNF4 + ubiquitin
- 3oj4 – hUbc D1 + tumor necrosis factor α-induced protein 3 + ubiquitin
- Ubiquitin conjugating enzyme D2
- 2esk, 2clw, 3l1y, 3tgd – hUbc D2
- 2eso, 2esp, 2esq – hUbc D2 (mutant)
- 1w4u – hUbc D2 - NMR
- 4ddg, 4ddi, 5ulf – hUbc D2 + ubiquitin
- 5ulf, 3a33 – hUbc D2 (mutant) + ubiquitin
- 4ldt – hUbc D2 + Otub1 + ubiquitin
- 5d1k, 5d1l, 5d1m – hUbc D2 + E3 ubiquitin-protein ligase RNF25
- 5edv – hUbc D2 + ubiquitin + E3 ubiquitin-protein ligase RNF31
- 4a49 – hUbc D2 + E3 ubiquitin-protein ligase CBL-B
- 4v3k, 4v3l, 4a4b, 4a4c – hUbc D2 + ZAP peptide + E3 ubiquitin-protein ligase CBL-B
- 3zni, 6w9d, 6w7z, 5ulh, 5vzw, 5zbu – hUbc D2 + ubiquitin + E3 ubiquitin-protein ligase
- 6sqo, 6sqs, 6sqr – hUbc D2 + ubiquitin-RPS27a + E3 ubiquitin-protein ligase Mdm2
- 5ulh, 5ulk – hUbc D2 (mutant) + ubiquitin + E3 ubiquitin-protein ligase RNF165
- 5mnj – hUbc D2 (mutant) + UBB + Mdm2 + Mdm4
- 5d0k, 5d0m – hUbc D2 + UBB + RING finger protein 165
- 4ldt – hUbc D2 (mutant) + ubiquitin + otub1 + ubiquitin aldehyde
- 4wz3 – hUbc D2 + E3 ubiquitin-protein ligase LubX
- 5v2w – hUbc D2 (mutant) + ubiquitin + TRIM23
- 1ur6 – hUbc D2 + Cnot4 - NMR
- 4auq, 6hpr – hUbc D2 (mutant) + baculoviral IAP repeat-containing protein + ubiquitin
- 3jvz, 3jw0 – hUbc D2 (mutant) + E3 NEDD4-2 + ubiquitin
- 6ttu – hUbc D2 in Cullin RING E3 ligase- Cryo EM
- 3eb6 – fUbc D2 + baculoviral IAP repeat-containing protein- frog
- Ubiquitin conjugating enzyme D3
- 5egg, 1x23 – hUbc D3
- 5ifr – hUbc D3 + ubiquitin
- 2fuh – hUbc D3 + ubiquitin - NMR
- 3ugb – hUbc D3 (mutant) + ubiquitin
- 3l1z – hUbc D3 + ubiquitin conjugating factor
- 4s3o, 3rpg – hUbc D3 + polycomb group ring finger protein + E3 ubiquitin-protein ligase RING2
- 4bvu – hUbc D3 + OspG + ubiquitin
- 6cp0 – hUbc D3 + SdcA
- 6t7f – hUbc D3 + ubiquitin + E3 ubiquitin-protein ligase MYCBP2
- Ubiquitin conjugating enzyme E1
- 3bzh – hUbc E1
- 6fga – hUbc E1 + E3 TRIM21
- Ubiquitin conjugating enzyme E2
- Ubiquitin conjugating enzyme G1
- 6d68 – hUbc G1 + ubiquitin
- Ubiquitin conjugating enzyme G2
- 2cyx – hUbc
- 2kly – hUbc - NMR
- 3fsh – hUbc + autocrine motility factor receptor
- 2lxp – hUbc + AMFR peptide - NMR
- 3h8k, 4lad – hUbc + AMFR peptide
- Ubiquitin conjugating enzyme H
- Ubiquitin conjugating enzyme J2
- Ubiquitin conjugating enzyme K
6jb6, 6jb7 – hUbc (mutant) + ubiquitin
- Ubiquitin conjugating enzyme Q1
- Ubiquitin conjugating enzyme R1
- 3rz3 – hUbc + inhibitor
- 4mdk – hUbc + ubiquitin + inhibitor
- Ubiquitin conjugating enzyme R2
- 6nyo – hUbc R2 + ubiquitin
- Ubiquitin conjugating enzyme S
- Ubiquitin conjugating enzyme T
- 6r75 – hUbc T (mutant)
- 4ccg – hUbc T + E3 ubiquitin-protein ligase Fancl
- Ubiquitin conjugating enzyme Uev-1
- 2a4d – hUbc catalytic domain
- 2hlw – hUbc catalytic domain - NMR
- 3e95 – PfUbc + ubiquitin carrier protein
- Ubiquitin conjugating enzyme Z
- Ubiquitin conjugating enzyme E2-18KDa
- 6op8 – fyUbc + CUE domain-containing protein 4
- Ubiquitin conjugating enzyme E2-25KDa (Huntington interacting protein 2 HIP-2)
ReferencesReferences
- ↑ Markson G, Kiel C, Hyde R, Brown S, Charalabous P, Bremm A, Semple J, Woodsmith J, Duley S, Salehi-Ashtiani K, Vidal M, Komander D, Serrano L, Lehner P, Sanderson CM. Analysis of the human E2 ubiquitin conjugating enzyme protein interaction network. Genome Res. 2009 Oct;19(10):1905-11. Epub 2009 Jun 23. PMID:19549727 doi:http://dx.doi.org/gr.093963.109
- ↑ Eddins MJ, Carlile CM, Gomez KM, Pickart CM, Wolberger C. Mms2-Ubc13 covalently bound to ubiquitin reveals the structural basis of linkage-specific polyubiquitin chain formation. Nat Struct Mol Biol. 2006 Oct;13(10):915-20. Epub 2006 Sep 17. PMID:16980971 doi:10.1038/nsmb1148
- ↑ Huang H, Kahana A, Gottschling DE, Prakash L, Liebman SW. The ubiquitin-conjugating enzyme Rad6 (Ubc2) is required for silencing in Saccharomyces cerevisiae. Mol Cell Biol. 1997 Nov;17(11):6693-9. PMID:9343433
- ↑ Seufert W, Jentsch S. Ubiquitin-conjugating enzymes UBC4 and UBC5 mediate selective degradation of short-lived and abnormal proteins. EMBO J. 1990 Feb;9(2):543-50. PMID:2154373
- ↑ Lenk U, Yu H, Walter J, Gelman MS, Hartmann E, Kopito RR, Sommer T. A role for mammalian Ubc6 homologues in ER-associated protein degradation. J Cell Sci. 2002 Jul 15;115(Pt 14):3007-14. PMID:12082160
- ↑ Yamamoto M, Okamoto T, Takeda K, Sato S, Sanjo H, Uematsu S, Saitoh T, Yamamoto N, Sakurai H, Ishii KJ, Yamaoka S, Kawai T, Matsuura Y, Takeuchi O, Akira S. Key function for the Ubc13 E2 ubiquitin-conjugating enzyme in immune receptor signaling. Nat Immunol. 2006 Sep;7(9):962-70. doi: 10.1038/ni1367. Epub 2006 Jul 23. PMID:16862162 doi:http://dx.doi.org/10.1038/ni1367
- ↑ Kim KI, Giannakopoulos NV, Virgin HW, Zhang DE. Interferon-inducible ubiquitin E2, Ubc8, is a conjugating enzyme for protein ISGylation. Mol Cell Biol. 2004 Nov;24(21):9592-600. doi: 10.1128/MCB.24.21.9592-9600.2004. PMID:15485925 doi:http://dx.doi.org/10.1128/MCB.24.21.9592-9600.2004
- ↑ Tahmasebi S, Ghorbani M, Savage P, Gocevski G, Yang XJ. The SUMO conjugating enzyme Ubc9 is required for inducing and maintaining stem cell pluripotency. Stem Cells. 2014 Apr;32(4):1012-20. doi: 10.1002/stem.1600. PMID:24706591 doi:http://dx.doi.org/10.1002/stem.1600
- ↑ Tatham MH, Plechanovova A, Jaffray EG, Salmen H, Hay RT. Ube2W conjugates ubiquitin to alpha-amino groups of protein N-termini. Biochem J. 2013 Jul 1;453(1):137-45. doi: 10.1042/BJ20130244. PMID:23560854 doi:http://dx.doi.org/10.1042/BJ20130244
- ↑ Shafiee SM, Rasti M, Seghatoleslam A, Azimi T, Owji AA. UBE2Q1 in a Human Breast Carcinoma Cell Line: Overexpression and Interaction with p53. Asian Pac J Cancer Prev. 2015;16(9):3723-7. PMID:25987028
- ↑ Martin I, Vourc'h P, Mahe M, Thepault RA, Antar C, Vedrine S, Praline J, Camu W, Andres CR, Corcia P. Association study of the ubiquitin conjugating enzyme gene UBE2H in sporadic ALS. Amyotroph Lateral Scler. 2009 Oct-Dec;10(5-6):432-5. doi:, 10.3109/17482960802444972. PMID:19922136 doi:http://dx.doi.org/10.3109/17482960802444972
- ↑ Middleton AJ, Day CL. The molecular basis of lysine 48 ubiquitin chain synthesis by Ube2K. Sci Rep. 2015 Nov 23;5:16793. doi: 10.1038/srep16793. PMID:26592444 doi:http://dx.doi.org/10.1038/srep16793
- ↑ Paul A, Wang B. RNF8- and Ube2S-Dependent Ubiquitin Lysine 11-Linkage Modification in Response to DNA Damage. Mol Cell. 2017 May 18;66(4):458-472.e5. doi: 10.1016/j.molcel.2017.04.013. PMID:28525740 doi:http://dx.doi.org/10.1016/j.molcel.2017.04.013
- ↑ Machida YJ, Machida Y, Chen Y, Gurtan AM, Kupfer GM, D'Andrea AD, Dutta A. UBE2T is the E2 in the Fanconi anemia pathway and undergoes negative autoregulation. Mol Cell. 2006 Aug;23(4):589-96. PMID:16916645 doi:http://dx.doi.org/10.1016/j.molcel.2006.06.024
- ↑ Schelpe J, Monte D, Dewitte F, Sixma TK, Rucktooa P. Structure of UBE2Z provides functional insight into specificity in the FAT10 conjugation machinery. J Biol Chem. 2015 Nov 10. pii: jbc.M115.671545. PMID:26555268 doi:http://dx.doi.org/10.1074/jbc.M115.671545
- ↑ Song S, Kim SY, Hong YM, Jo DG, Lee JY, Shim SM, Chung CW, Seo SJ, Yoo YJ, Koh JY, Lee MC, Yates AJ, Ichijo H, Jung YK. Essential role of E2-25K/Hip-2 in mediating amyloid-beta neurotoxicity. Mol Cell. 2003 Sep;12(3):553-63. PMID:14527403
- ↑ Sancho E, Vila MR, Sanchez-Pulido L, Lozano JJ, Paciucci R, Nadal M, Fox M, Harvey C, Bercovich B, Loukili N, Ciechanover A, Lin SL, Sanz F, Estivill X, Valencia A, Thomson TM. Role of UEV-1, an inactive variant of the E2 ubiquitin-conjugating enzymes, in in vitro differentiation and cell cycle behavior of HT-29-M6 intestinal mucosecretory cells. Mol Cell Biol. 1998 Jan;18(1):576-89. PMID:9418904
- ↑ Wu X, Zhang W, Font-Burgada J, Palmer T, Hamil AS, Biswas SK, Poidinger M, Borcherding N, Xie Q, Ellies LG, Lytle NK, Wu LW, Fox RG, Yang J, Dowdy SF, Reya T, Karin M. Ubiquitin-conjugating enzyme Ubc13 controls breast cancer metastasis through a TAK1-p38 MAP kinase cascade. Proc Natl Acad Sci U S A. 2014 Sep 23;111(38):13870-5. doi:, 10.1073/pnas.1414358111. Epub 2014 Sep 4. PMID:25189770 doi:http://dx.doi.org/10.1073/pnas.1414358111
- ↑ Bosanac I, Phu L, Pan B, Zilberleyb I, Maurer B, Dixit VM, Hymowitz SG, Kirkpatrick DS. Modulation of K11-Linkage Formation by Variable Loop Residues within UbcH5A. J Mol Biol. 2011 May 6;408(3):420-31. Epub 2011 Mar 10. PMID:21396940 doi:10.1016/j.jmb.2011.03.011