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 participates 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 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 D3 functions in the ubiquitination of the tumor suppressor p53.
Medical importanceUBC13 is required for metastatic spread and lung colonizationin breast cancer[10].
Structural highlightsThe active site of Ubc contains a cysteine residue. The [11].
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3D Structures of ubiquitin conjugating enzyme3D Structures of ubiquitin conjugating enzyme
Updated on 03-October-2018
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- Ubiquitin conjugating enzyme
- 2aak – AtUbc – Arabidopsis thaliana
- 2e2c – Ubc – Spisula solidissima
- 1q34 – CeUbc – Caenorhabidis elegans
- 1jas – hUbc – human
- 2fo3 – Ubc – Plasmodium vivax
- 2h2y – PfUbc – Plasmodium falciparum
- 1fxt – yUbc + ubiquitin
- Ubiquitin conjugating enzyme 1
- Ubiquitin conjugating enzyme 2
- 1ayz – yUbc
- 1z2u – CeUbc
- 4r62 – yUbc + ubiquitin carboxyl extension protein 80
- 5aie – yUbc + NOT4
- Ubiquitin conjugating enzyme 4
- 1qcq – yUbc
- 4ii2 – fyUbc (mutant) + E1 + ATP – fission yeast
- 5aie – yUbc + NOT4 RING domain
- Ubiquitin conjugating enzyme 6
- 4jjq – hUbc + ubiquitin carboxyl terminal hydrolase
- Ubiquitin conjugating enzyme 7 or Ubc L3
- 2ucz – yUbc
- 2awf, 2cyx – hUbc
- 1c4z – hUbc + E3 HECT domain
- 1fbv – hUbc + E3 Cbl + ZAP-70 peptide
- 4jqu – hUbc + U7BR
- 3sqv – hUbc + secreted effector protein
- 3sy2 – hUbc + E3 Sopa
- 4q5e, 4q5h – hUbc (mutant) + ubiquitin + OspG
- 6cp2 – hUbc (mutant) + UBB + SidC
- 6djw, 6djx – hUbc (mutant) + ubiquitin + PARKIN
- 5tte, 5udh – hUbc (mutant) + ubiquitin + ARIH1
- 5hpt – hUbc + ubiquitin + NEDD4-like E3 ubiquitin-protein
- 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)
- 3o2u – yUbc
- 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
- 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 – CeUbc + OTUB1
- 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
- 4dhj – hUbc + ubiquitin + OTUB1
- 4whv – hUbc + ubiquitin + E3 ubiquitin-protein ligase RNF8
- 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
- Ubiquitin conjugating enzyme 16 or Ubc W
- 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 – 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 – 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 – hUbc D2 + ubiquitin + E3 ubiquitin-protein ligase RNF38
- 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 – hUbc D2 (mutant) + baculoviral IAP repeat-containing protein + ubiquitin
- 3jvz, 3jw0 – hUbc D2 (mutant) + E3 NEDD4-2 + ubiquitin
- 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
- Ubiquitin conjugating enzyme E1
- 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
- Ubiquitin conjugating enzyme Q
- Ubiquitin conjugating enzyme R1
- 3rz3 – hUbc + inhibitor
- 4mdk – hUbc + ubiquitin + inhibitor
- Ubiquitin conjugating enzyme S
- Ubiquitin conjugating enzyme T
- 4ccg – hUbc + 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 E2-25KDa (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
- ↑ 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