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PDBsum entry 1c4z

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protein Protein-protein interface(s) links
Ligase PDB id
1c4z
Jmol
Contents
Protein chains
350 a.a. *
144 a.a. *
Waters ×359
* Residue conservation analysis
PDB id:
1c4z
Name: Ligase
Title: Structure of e6ap: insights into ubiquitination pathway
Structure: Ubiquitin-protein ligase e3a. Chain: a, b, c. Fragment: hect catalytic domain. Synonym: e6ap. Engineered: yes. Ubiquitin conjugating enzyme e2. Chain: d. Synonym: ubch7. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PQS)
Resolution:
2.60Å     R-factor:   0.237     R-free:   0.290
Authors: L.Huang,E.Kinnucan,G.Wang,S.Beaudenon,P.M.Howley, J.M.Huibregtse,N.P.Pavletich
Key ref:
L.Huang et al. (1999). Structure of an E6AP-UbcH7 complex: insights into ubiquitination by the E2-E3 enzyme cascade. Science, 286, 1321-1326. PubMed id: 10558980 DOI: 10.1126/science.286.5443.1321
Date:
14-Oct-99     Release date:   17-Nov-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q05086  (UBE3A_HUMAN) -  Ubiquitin-protein ligase E3A
Seq:
Struc:
 
Seq:
Struc:
875 a.a.
350 a.a.
Protein chain
Pfam   ArchSchema ?
P68036  (UB2L3_HUMAN) -  Ubiquitin-conjugating enzyme E2 L3
Seq:
Struc:
154 a.a.
144 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chain D: E.C.6.3.2.19  - Ubiquitin--protein ligase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine
ATP
+ ubiquitin
+ protein lysine
= AMP
+ diphosphate
+ protein N-ubiquityllysine
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     ubiquitin ligase complex   4 terms 
  Biological process     protein K11-linked ubiquitination   10 terms 
  Biochemical function     nucleotide binding     10 terms  

 

 
    reference    
 
 
DOI no: 10.1126/science.286.5443.1321 Science 286:1321-1326 (1999)
PubMed id: 10558980  
 
 
Structure of an E6AP-UbcH7 complex: insights into ubiquitination by the E2-E3 enzyme cascade.
L.Huang, E.Kinnucan, G.Wang, S.Beaudenon, P.M.Howley, J.M.Huibregtse, N.P.Pavletich.
 
  ABSTRACT  
 
The E6AP ubiquitin-protein ligase (E3) mediates the human papillomavirus-induced degradation of the p53 tumor suppressor in cervical cancer and is mutated in Angelman syndrome, a neurological disorder. The crystal structure of the catalytic hect domain of E6AP reveals a bilobal structure with a broad catalytic cleft at the junction of the two lobes. The cleft consists of conserved residues whose mutation interferes with ubiquitin-thioester bond formation and is the site of Angelman syndrome mutations. The crystal structure of the E6AP hect domain bound to the UbcH7 ubiquitin-conjugating enzyme (E2) reveals the determinants of E2-E3 specificity and provides insights into the transfer of ubiquitin from the E2 to the E3.
 
  Selected figure(s)  
 
Figure 2.
Fig. 2. The E6AP catalytic cysteine (Cys820) maps to the interface between the N and C lobes of the hect domain. Residues of the active-site loop and those that make N-C lobe contacts are shown in yellow. N and C lobes are colored red and green, respectively. The hinge region (residues 738 to 740) between the N and C lobes is colored white. White dashed lines indicate hydrogen bonds; red atoms, oxygen; blue, nitrogen; green, sulfur.
Figure 3.
Fig. 3. A broad cleft at the interface of the N and C lobes contains highly conserved residues whose mutation reduces the formation of the thioester or isopeptide bond. (A) The molecular surface of the E6AP hect domain is colored according to the conservation in 18 hect sequences: human E6AP, Nedd4, y032, tr12, rat Urb1, Saccharomyces pombe Pub1, all five hect E3s of Saccharomyces cerevisiae (Rsp5, Tom1, Ufd4, Hul4, and Hul5), four hect proteins from Caenorhabditis elegans (GenBank accession numbers BAA21847, CAA19508, CAA86773, and CAA91061), and two Drosophila melanogaster hect proteins (the hyperplastic disc protein and one with GenBank accession number AAD38975). The two views are related by a rotation of ~80° about the vertical axis. The view on the left has an orientation similar to that of Fig. 1A; that on the right is similar to Fig. 2. The position of the broad cleft is approximately marked by a black line. [Prepared with the program GRASP (43).] (B) Close-up view of the broad cleft. The N and C lobes of the hect domain are colored red and green, respectively. The hinge region (738 to 740) between the N and C lobes is white; the conserved side chains are yellow. The residues mutated in Angelman syndrome are indicated with white spheres. Orientation is similar to that of Fig. 1A.
 
  The above figures are reprinted by permission from the AAAs: Science (1999, 286, 1321-1326) copyright 1999.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids.
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20980253 D.Y.Lin, J.Diao, D.Zhou, and J.Chen (2011).
Biochemical and structural studies of a HECT-like ubiquitin ligase from Escherichia coli O157:H7.
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PDB codes: 3naw 3nb2
21399620 E.Maspero, S.Mari, E.Valentini, A.Musacchio, A.Fish, S.Pasqualato, and S.Polo (2011).
Structure of the HECT:ubiquitin complex and its role in ubiquitin chain elongation.
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PDB codes: 2xbb 2xbf
21399621 H.C.Kim, A.M.Steffen, M.L.Oldham, J.Chen, and J.M.Huibregtse (2011).
Structure and function of a HECT domain ubiquitin-binding site.
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PDB code: 3olm
21332354 J.H.Hurley, and H.Stenmark (2011).
Molecular mechanisms of ubiquitin-dependent membrane traffic.
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19557013 A.G.Eldridge, and T.O'Brien (2010).
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19557014 B.Yang, and S.Kumar (2010).
Nedd4 and Nedd4-2: closely related ubiquitin-protein ligases with distinct physiological functions.
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21158740 D.M.Wenzel, K.E.Stoll, and R.E.Klevit (2010).
E2s: structurally economical and functionally replete.
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Crystal structure of UbcH5b~ubiquitin intermediate: insight into the formation of the self-assembled E2~Ub conjugates.
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PDB code: 3a33
20974935 G.Guntas, C.Purbeck, and B.Kuhlman (2010).
Engineering a protein-protein interface using a computationally designed library.
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Identification of an unconventional E3 binding surface on the UbcH5 ~ Ub conjugate recognized by a pathogenic bacterial E3 ligase.
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19722269 P.Radivojac, V.Vacic, C.Haynes, R.R.Cocklin, A.Mohan, J.W.Heyen, M.G.Goebl, and L.M.Iakoucheva (2010).
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20804422 P.S.Andrews, S.Schneider, E.Yang, M.Michaels, H.Chen, J.Tang, and R.Emkey (2010).
Identification of substrates of SMURF1 ubiquitin ligase activity utilizing protein microarrays.
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20696396 R.C.Benirschke, J.R.Thompson, Y.Nominé, E.Wasielewski, N.Juranić, S.Macura, S.Hatakeyama, K.I.Nakayama, M.V.Botuyan, and G.Mer (2010).
Molecular basis for the association of human E4B U box ubiquitin ligase with E2-conjugating enzymes UbcH5c and Ubc4.
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PDB codes: 2kre 3l1x 3l1y 3l1z
20007713 R.K.Pandya, J.R.Partridge, K.R.Love, T.U.Schwartz, and H.L.Ploegh (2010).
A structural element within the HUWE1 HECT domain modulates self-ubiquitination and substrate ubiquitination activities.
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PDB code: 3h1d
20036613 S.W.Hicks, and J.E.Galán (2010).
Hijacking the host ubiquitin pathway: structural strategies of bacterial E3 ubiquitin ligases.
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19436320 D.Rotin, and S.Kumar (2009).
Physiological functions of the HECT family of ubiquitin ligases.
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19664228 E.A.Whitcomb, and A.Taylor (2009).
Ubiquitin control of S phase: a new role for the ubiquitin conjugating enzyme, UbcH7.
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18946090 E.A.Whitcomb, E.J.Dudek, Q.Liu, and A.Taylor (2009).
Novel control of S phase of the cell cycle by ubiquitin-conjugating enzyme H7.
  Mol Biol Cell, 20, 1-9.  
19101823 G.Liu, F.Forouhar, A.Eletsky, H.S.Atreya, J.M.Aramini, R.Xiao, Y.J.Huang, M.Abashidze, J.Seetharaman, J.Liu, B.Rost, T.Acton, G.T.Montelione, J.F.Hunt, and T.Szyperski (2009).
NMR and X-RAY structures of human E2-like ubiquitin-fold modifier conjugating enzyme 1 (UFC1) reveal structural and functional conservation in the metazoan UFM1-UBA5-UFC1 ubiquination pathway.
  J Struct Funct Genomics, 10, 127-136.
PDB codes: 2k07 3e2g 3evx
20064473 H.B.Kamadurai, J.Souphron, D.C.Scott, D.M.Duda, D.J.Miller, D.Stringer, R.C.Piper, and B.A.Schulman (2009).
Insights into ubiquitin transfer cascades from a structure of a UbcH5B approximately ubiquitin-HECT(NEDD4L) complex.
  Mol Cell, 36, 1095-1102.
PDB codes: 3jvz 3jw0
19364824 H.C.Kim, and J.M.Huibregtse (2009).
Polyubiquitination by HECT E3s and the determinants of chain type specificity.
  Mol Cell Biol, 29, 3307-3318.  
19274063 H.Xu, W.Wang, C.Li, H.Yu, A.Yang, B.Wang, and Y.Jin (2009).
WWP2 promotes degradation of transcription factor OCT4 in human embryonic stem cells.
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19744925 J.R.Lee, A.J.Oestreich, J.A.Payne, M.S.Gunawan, A.P.Norgan, and D.J.Katzmann (2009).
The HECT domain of the ubiquitin ligase Rsp5 contributes to substrate recognition.
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19350571 J.Zhao, Z.Zhang, Z.Vucetic, K.J.Soprano, and D.R.Soprano (2009).
HACE1: A novel repressor of RAR transcriptional activity.
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19256485 K.S.Plafker, J.D.Singer, and S.M.Plafker (2009).
The ubiquitin conjugating enzyme, UbcM2, engages in novel interactions with components of cullin-3 based E3 ligases.
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Regulation of the RSP5 ubiquitin ligase by an intrinsic ubiquitin-binding site.
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19690564 S.J.van Wijk, S.J.de Vries, P.Kemmeren, A.Huang, R.Boelens, A.M.Bonvin, and H.T.Timmers (2009).
A comprehensive framework of E2-RING E3 interactions of the human ubiquitin-proteasome system.
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19337321 S.Jackson, and Y.Xiong (2009).
Targeting protein ubiquitylation: DDB1 takes its RING off.
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20011534 W.Lee, Y.Zhang, K.Mukhyala, R.A.Lazarus, and Z.Zhang (2009).
Bi-directional SIFT predicts a subset of activating mutations.
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19686682 X.Zhao, D.D' Arca, W.K.Lim, M.Brahmachary, M.S.Carro, T.Ludwig, C.C.Cardo, F.Guillemot, K.Aldape, A.Califano, A.Iavarone, and A.Lasorella (2009).
The N-Myc-DLL3 cascade is suppressed by the ubiquitin ligase Huwe1 to inhibit proliferation and promote neurogenesis in the developing brain.
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19575579 Y.Zhang, Z.Zhao, and Y.Xue (2009).
Roles of proteolysis in plant self-incompatibility.
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18477634 A.Nigham, L.Tucker-Kellogg, I.Mihalek, C.Verma, and D.Hsu (2008).
pFlexAna: detecting conformational changes in remotely related proteins.
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18515172 I.E.Wertz, and V.M.Dixit (2008).
Ubiquitin-mediated regulation of TNFR1 signaling.
  Cytokine Growth Factor Rev, 19, 313-324.  
18408014 J.A.Tan, Y.Sun, J.Song, Y.Chen, T.G.Krontiris, and L.K.Durrin (2008).
SUMO conjugation to the matrix attachment region-binding protein, special AT-rich sequence-binding protein-1 (SATB1), targets SATB1 to promyelocytic nuclear bodies where it undergoes caspase cleavage.
  J Biol Chem, 283, 18124-18134.  
18066077 J.Diao, Y.Zhang, J.M.Huibregtse, D.Zhou, and J.Chen (2008).
Crystal structure of SopA, a Salmonella effector protein mimicking a eukaryotic ubiquitin ligase.
  Nat Struct Mol Biol, 15, 65-70.
PDB codes: 2qyu 2qza
18641638 K.Lu, X.Yin, T.Weng, S.Xi, L.Li, G.Xing, X.Cheng, X.Yang, L.Zhang, and F.He (2008).
Targeting WW domains linker of HECT-type ubiquitin ligase Smurf1 for activation by CKIP-1.
  Nat Cell Biol, 10, 994.  
18583345 L.A.Durfee, M.L.Kelley, and J.M.Huibregtse (2008).
The basis for selective E1-E2 interactions in the ISG15 conjugation system.
  J Biol Chem, 283, 23895-23902.  
19007434 S.Beaudenon, and J.M.Huibregtse (2008).
HPV E6, E6AP and cervical cancer.
  BMC Biochem, 9, S4.  
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E6-associated protein (E6-AP) is a dual function coactivator of steroid hormone receptors.
  Nucl Recept Signal, 6, e006.  
18511420 W.S.Brooks, E.S.Helton, S.Banerjee, M.Venable, L.Johnson, T.R.Schoeb, R.A.Kesterson, and D.F.Crawford (2008).
G2E3 is a dual function ubiquitin ligase required for early embryonic development.
  J Biol Chem, 283, 22304-22315.  
18043262 W.Wang, and W.S.El-Deiry (2008).
Restoration of p53 to limit tumor growth.
  Curr Opin Oncol, 20, 90-96.  
18701717 Y.Wu, F.V.Bolduc, K.Bell, T.Tully, Y.Fang, A.Sehgal, and J.A.Fischer (2008).
A Drosophila model for Angelman syndrome.
  Proc Natl Acad Sci U S A, 105, 12399-12404.  
18997779 Y.Zhu, H.Li, L.Hu, J.Wang, Y.Zhou, Z.Pang, L.Liu, and F.Shao (2008).
Structure of a Shigella effector reveals a new class of ubiquitin ligases.
  Nat Struct Mol Biol, 15, 1302-1308.
PDB code: 3cvr
18492068 Z.Tang, C.M.Hecker, A.Scheschonka, and H.Betz (2008).
Protein interactions in the sumoylation cascade: lessons from X-ray structures.
  FEBS J, 275, 3003-3015.  
17420471 A.A.Horwitz, e.l. .B.Affar, G.F.Heine, Y.Shi, and J.D.Parvin (2007).
A mechanism for transcriptional repression dependent on the BRCA1 E3 ubiquitin ligase.
  Proc Natl Acad Sci U S A, 104, 6614-6619.  
17919899 A.D.Capili, and C.D.Lima (2007).
Taking it step by step: mechanistic insights from structural studies of ubiquitin/ubiquitin-like protein modification pathways.
  Curr Opin Struct Biol, 17, 726-735.  
17418786 B.P.Somesh, S.Sigurdsson, H.Saeki, H.Erdjument-Bromage, P.Tempst, and J.Q.Svejstrup (2007).
Communication between distant sites in RNA polymerase II through ubiquitylation factors and the polymerase CTD.
  Cell, 129, 57-68.  
17477837 B.T.Dye, and B.A.Schulman (2007).
Structural mechanisms underlying posttranslational modification by ubiquitin-like proteins.
  Annu Rev Biophys Biomol Struct, 36, 131-150.  
17873885 D.E.Christensen, P.S.Brzovic, and R.E.Klevit (2007).
E2-BRCA1 RING interactions dictate synthesis of mono- or specific polyubiquitin chain linkages.
  Nat Struct Mol Biol, 14, 941-948.  
17603074 D.W.Sammond, Z.M.Eletr, C.Purbeck, R.J.Kimple, D.P.Siderovski, and B.Kuhlman (2007).
Structure-based protocol for identifying mutations that enhance protein-protein binding affinities.
  J Mol Biol, 371, 1392-1404.
PDB code: 2om2
17672887 G.Mayr, F.S.Domingues, and P.Lackner (2007).
Comparative analysis of protein structure alignments.
  BMC Struct Biol, 7, 50.  
18047743 M.Scheffner, and O.Staub (2007).
HECT E3s and human disease.
  BMC Biochem, 8, S6.  
17170710 M.V.Poyurovsky, C.Priest, A.Kentsis, K.L.Borden, Z.Q.Pan, N.Pavletich, and C.Prives (2007).
The Mdm2 RING domain C-terminus is required for supramolecular assembly and ubiquitin ligase activity.
  EMBO J, 26, 90.  
17149774 N.Arden, B.S.Majors, S.H.Ahn, G.Oyler, and M.J.Betenbaugh (2007).
Inhibiting the apoptosis pathway using MDM2 in mammalian cell cultures.
  Biotechnol Bioeng, 97, 601-614.  
17236139 P.S.Tarpey, F.L.Raymond, S.O'Meara, S.Edkins, J.Teague, A.Butler, E.Dicks, C.Stevens, C.Tofts, T.Avis, S.Barthorpe, G.Buck, J.Cole, K.Gray, K.Halliday, R.Harrison, K.Hills, A.Jenkinson, D.Jones, A.Menzies, T.Mironenko, J.Perry, K.Raine, D.Richardson, R.Shepherd, A.Small, J.Varian, S.West, S.Widaa, U.Mallya, J.Moon, Y.Luo, S.Holder, S.F.Smithson, J.A.Hurst, J.Clayton-Smith, B.Kerr, J.Boyle, M.Shaw, L.Vandeleur, J.Rodriguez, R.Slaugh, D.F.Easton, R.Wooster, M.Bobrow, A.K.Srivastava, R.E.Stevenson, C.E.Schwartz, G.Turner, J.Gecz, P.A.Futreal, M.R.Stratton, and M.Partington (2007).
Mutations in CUL4B, which encodes a ubiquitin E3 ligase subunit, cause an X-linked mental retardation syndrome associated with aggressive outbursts, seizures, relative macrocephaly, central obesity, hypogonadism, pes cavus, and tremor.
  Am J Hum Genet, 80, 345-352.  
17894347 S.Chaudhury, A.Sircar, A.Sivasubramanian, M.Berrondo, and J.J.Gray (2007).
Incorporating biochemical information and backbone flexibility in RosettaDock for CAPRI rounds 6-12.
  Proteins, 69, 793-800.  
17803232 S.Qin, and H.X.Zhou (2007).
A holistic approach to protein docking.
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17160626 X.Gu, F.Zhao, M.Zheng, X.Fei, X.Chen, S.Huang, Y.Xie, and Y.Mao (2007).
Cloning and characterization of a gene encoding the human putative ubiquitin conjugating enzyme E2Z (UBE2Z).
  Mol Biol Rep, 34, 183-188.  
17433711 Y.C.Liu (2007).
The E3 ubiquitin ligase Itch in T cell activation, differentiation, and tolerance.
  Semin Immunol, 19, 197-205.  
  20103862 Y.Chen (2007).
The enzymes in ubiquitin-like post-translational modifications.
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17240353 Y.Kee, and J.M.Huibregtse (2007).
Regulation of catalytic activities of HECT ubiquitin ligases.
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17131388 Y.Yang, W.Liu, W.Zou, H.Wang, H.Zong, J.Jiang, Y.Wang, and J.Gu (2007).
Ubiquitin-dependent proteolysis of trihydrophobin 1 (TH1) by the human papilloma virus E6-associated protein (E6-AP).
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17433363 Z.M.Eletr, and B.Kuhlman (2007).
Sequence determinants of E2-E6AP binding affinity and specificity.
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16337426 A.B.Fotia, D.I.Cook, and S.Kumar (2006).
The ubiquitin-protein ligases Nedd4 and Nedd4-2 show similar ubiquitin-conjugating enzyme specificities.
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16816840 G.Nalepa, M.Rolfe, and J.W.Harper (2006).
Drug discovery in the ubiquitin-proteasome system.
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16413479 M.Hochstrasser (2006).
Lingering mysteries of ubiquitin-chain assembly.
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  16582478 R.Arai, S.Yoshikawa, K.Murayama, Y.Imai, R.Takahashi, M.Shirouzu, and S.Yokoyama (2006).
Structure of human ubiquitin-conjugating enzyme E2 G2 (UBE2G2/UBC7).
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 330-334.
PDB code: 2cyx
16462746 S.Lee, Y.C.Tsai, R.Mattera, W.J.Smith, M.S.Kostelansky, A.M.Weissman, J.S.Bonifacino, and J.H.Hurley (2006).
Structural basis for ubiquitin recognition and autoubiquitination by Rabex-5.
  Nat Struct Mol Biol, 13, 264-271.
PDB codes: 2fid 2fif
16061177 A.A.Ogunjimi, D.J.Briant, N.Pece-Barbara, C.Le Roy, G.M.Di Guglielmo, P.Kavsak, R.K.Rasmussen, B.T.Seet, F.Sicheri, and J.L.Wrana (2005).
Regulation of Smurf2 ubiquitin ligase activity by anchoring the E2 to the HECT domain.
  Mol Cell, 19, 297-308.
PDB code: 1zvd
15723079 A.Pichler, P.Knipscheer, E.Oberhofer, W.J.van Dijk, R.Körner, J.V.Olsen, S.Jentsch, F.Melchior, and T.K.Sixma (2005).
SUMO modification of the ubiquitin-conjugating enzyme E2-25K.
  Nat Struct Mol Biol, 12, 264-269.
PDB codes: 2bep 2bf8
15684077 A.Vichi, D.M.Payne, G.Pacheco-Rodriguez, J.Moss, and M.Vaughan (2005).
E3 ubiquitin ligase activity of the trifunctional ARD1 (ADP-ribosylation factor domain protein 1).
  Proc Natl Acad Sci U S A, 102, 1945-1950.  
15989956 D.Chen, N.Kon, M.Li, W.Zhang, J.Qin, and W.Gu (2005).
ARF-BP1/Mule is a critical mediator of the ARF tumor suppressor.
  Cell, 121, 1071-1083.  
15931224 D.Reverter, and C.D.Lima (2005).
Insights into E3 ligase activity revealed by a SUMO-RanGAP1-Ubc9-Nup358 complex.
  Nature, 435, 687-692.
PDB code: 1z5s
15694336 D.T.Huang, A.Paydar, M.Zhuang, M.B.Waddell, J.M.Holton, and B.A.Schulman (2005).
Structural basis for recruitment of Ubc12 by an E2 binding domain in NEDD8's E1.
  Mol Cell, 17, 341-350.
PDB code: 1y8x
16365295 E.Ozkan, H.Yu, and J.Deisenhofer (2005).
Mechanistic insight into the allosteric activation of a ubiquitin-conjugating enzyme by RING-type ubiquitin ligases.
  Proc Natl Acad Sci U S A, 102, 18890-18895.
PDB codes: 2esk 2eso 2esp 2esq
15623582 J.Martin-Serrano, S.W.Eastman, W.Chung, and P.D.Bieniasz (2005).
HECT ubiquitin ligases link viral and cellular PPXY motifs to the vacuolar protein-sorting pathway.
  J Cell Biol, 168, 89.  
15608651 M.H.Tatham, S.Kim, E.Jaffray, J.Song, Y.Chen, and R.T.Hay (2005).
Unique binding interactions among Ubc9, SUMO and RanBP2 reveal a mechanism for SUMO paralog selection.
  Nat Struct Mol Biol, 12, 67-74.  
16341092 M.Wang, and C.M.Pickart (2005).
Different HECT domain ubiquitin ligases employ distinct mechanisms of polyubiquitin chain synthesis.
  EMBO J, 24, 4324-4333.  
16219697 S.Matsuzawa, M.Cuddy, T.Fukushima, and J.C.Reed (2005).
Method for targeting protein destruction by using a ubiquitin-independent, proteasome-mediated degradation pathway.
  Proc Natl Acad Sci U S A, 102, 14982-14987.  
16142244 Z.M.Eletr, D.T.Huang, D.M.Duda, B.A.Schulman, and B.Kuhlman (2005).
E2 conjugating enzymes must disengage from their E1 enzymes before E3-dependent ubiquitin and ubiquitin-like transfer.
  Nat Struct Mol Biol, 12, 933-934.  
14747994 B.M.Kus, C.E.Caldon, R.Andorn-Broza, and A.M.Edwards (2004).
Functional interaction of 13 yeast SCF complexes with a set of yeast E2 enzymes in vitro.
  Proteins, 54, 455-467.  
14993279 C.Debonneville, and O.Staub (2004).
Participation of the ubiquitin-conjugating enzyme UBE2E3 in Nedd4-2-dependent regulation of the epithelial Na+ channel.
  Mol Cell Biol, 24, 2397-2409.  
15062086 C.Dominguez, A.M.Bonvin, G.S.Winkler, F.M.van Schaik, H.T.Timmers, and R.Boelens (2004).
Structural model of the UbcH5B/CNOT4 complex revealed by combining NMR, mutagenesis, and docking approaches.
  Structure, 12, 633-644.
PDB code: 1ur6
14657247 D.J.Katzmann, S.Sarkar, T.Chu, A.Audhya, and S.D.Emr (2004).
Multivesicular body sorting: ubiquitin ligase Rsp5 is required for the modification and sorting of carboxypeptidase S.
  Mol Biol Cell, 15, 468-480.  
15361859 D.T.Huang, D.W.Miller, R.Mathew, R.Cassell, J.M.Holton, M.F.Roussel, and B.A.Schulman (2004).
A unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8.
  Nat Struct Mol Biol, 11, 927-935.
PDB code: 1tt5
15169876 J.Shackelford, and J.S.Pagano (2004).
Tumor viruses and cell signaling pathways: deubiquitination versus ubiquitination.
  Mol Cell Biol, 24, 5089-5093.  
15113913 K.J.Oh, A.Kalinina, J.Wang, K.Nakayama, K.I.Nakayama, and S.Bagchi (2004).
The papillomavirus E7 oncoprotein is ubiquitinated by UbcH7 and Cullin 1- and Skp2-containing E3 ligase.
  J Virol, 78, 5338-5346.  
15341722 P.J.Winn, T.L.Religa, J.N.Battey, A.Banerjee, and R.C.Wade (2004).
Determinants of functionality in the ubiquitin conjugating enzyme family.
  Structure, 12, 1563-1574.  
15367689 S.Verma, A.Ismail, X.Gao, G.Fu, X.Li, B.W.O'Malley, and Z.Nawaz (2004).
The ubiquitin-conjugating enzyme UBCH7 acts as a coactivator for steroid hormone receptors.
  Mol Cell Biol, 24, 8716-8726.  
15340381 T.Cardozo, and M.Pagano (2004).
The SCF ubiquitin ligase: insights into a molecular machine.
  Nat Rev Mol Cell Biol, 5, 739-751.  
15032575 Y.C.Liu (2004).
Ubiquitin ligases and the immune response.
  Annu Rev Immunol, 22, 81.  
12969426 B.P.Downes, R.M.Stupar, D.J.Gingerich, and R.D.Vierstra (2003).
The HECT ubiquitin-protein ligase (UPL) family in Arabidopsis: UPL3 has a specific role in trichome development.
  Plant J, 35, 729-742.  
12944097 B.R.Wong, F.Parlati, K.Qu, S.Demo, T.Pray, J.Huang, D.G.Payan, and M.K.Bennett (2003).
Drug discovery in the ubiquitin regulatory pathway.
  Drug Discov Today, 8, 746-754.  
14560004 F.Abe, and H.Iida (2003).
Pressure-induced differential regulation of the two tryptophan permeases Tat1 and Tat2 by ubiquitin ligase Rsp5 and its binding proteins, Bul1 and Bul2.
  Mol Cell Biol, 23, 7566-7584.  
12566516 J.Clayton-Smith, and L.Laan (2003).
Angelman syndrome: a review of the clinical and genetic aspects.
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12932734 L.Banks, D.Pim, and M.Thomas (2003).
Viruses and the 26S proteasome: hacking into destruction.
  Trends Biochem Sci, 28, 452-459.  
12535537 M.A.Verdecia, C.A.Joazeiro, N.J.Wells, J.L.Ferrer, M.E.Bowman, T.Hunter, and J.P.Noel (2003).
Conformational flexibility underlies ubiquitin ligation mediated by the WWP1 HECT domain E3 ligase.
  Mol Cell, 11, 249-259.
PDB code: 1nd7
12627222 M.D.Ohi, C.W.Vander Kooi, J.A.Rosenberg, W.J.Chazin, and K.L.Gould (2003).
Structural insights into the U-box, a domain associated with multi-ubiquitination.
  Nat Struct Biol, 10, 250-255.
PDB code: 1n87
12517333 N.Zheng (2003).
A closer look of the HECTic ubiquitin ligases.
  Structure, 11, 5-6.  
14517261 P.Y.Wu, M.Hanlon, M.Eddins, C.Tsui, R.S.Rogers, J.P.Jensen, M.J.Matunis, A.M.Weissman, A.M.Weisman, A.M.Weissman, C.Wolberger, C.P.Wolberger, and C.M.Pickart (2003).
A conserved catalytic residue in the ubiquitin-conjugating enzyme family.
  EMBO J, 22, 5241-5250.  
14608372 S.Neumann, E.Petfalski, B.Brügger, H.Grosshans, F.Wieland, D.Tollervey, and E.Hurt (2003).
Formation and nuclear export of tRNA, rRNA and mRNA is regulated by the ubiquitin ligase Rsp5p.
  EMBO Rep, 4, 1156-1162.  
12553912 S.Orlicky, X.Tang, A.Willems, M.Tyers, and F.Sicheri (2003).
Structural basis for phosphodependent substrate selection and orientation by the SCFCdc4 ubiquitin ligase.
  Cell, 112, 243-256.
PDB code: 1nex
12438698 A.Kentsis, R.E.Gordon, and K.L.Borden (2002).
Control of biochemical reactions through supramolecular RING domain self-assembly.
  Proc Natl Acad Sci U S A, 99, 15404-15409.  
12006492 O.Pornillos, S.L.Alam, R.L.Rich, D.G.Myszka, D.R.Davis, and W.I.Sundquist (2002).
Structure and functional interactions of the Tsg101 UEV domain.
  EMBO J, 21, 2397-2406.
PDB codes: 1kpp 1kpq
11823428 T.K.Albert, H.Hanzawa, Y.I.Legtenberg, M.J.de Ruwe, F.A.van den Heuvel, M.A.Collart, R.Boelens, and H.T.Timmers (2002).
Identification of a ubiquitin-protein ligase subunit within the CCR4-NOT transcription repressor complex.
  EMBO J, 21, 355-364.  
12531181 T.R.Pray, F.Parlati, J.Huang, B.R.Wong, D.G.Payan, M.K.Bennett, S.D.Issakani, S.Molineaux, and S.D.Demo (2002).
Cell cycle regulatory E3 ubiquitin ligases as anticancer targets.
  Drug Resist Updat, 5, 249-258.  
11440714 A.P.VanDemark, R.M.Hofmann, C.Tsui, C.M.Pickart, and C.Wolberger (2001).
Molecular insights into polyubiquitin chain assembly: crystal structure of the Mms2/Ubc13 heterodimer.
  Cell, 105, 711-720.
PDB codes: 1jat 1jbb
11336713 C.Gieffers, P.Dube, J.R.Harris, H.Stark, and J.M.Peters (2001).
Three-dimensional structure of the anaphase-promoting complex.
  Mol Cell, 7, 907-913.  
11395416 C.M.Pickart (2001).
Mechanisms underlying ubiquitination.
  Annu Rev Biochem, 70, 503-533.  
11533242 C.Ptak, C.Gwozd, J.T.Huzil, T.J.Gwozd, G.Garen, and M.J.Ellison (2001).
Creation of a pluripotent ubiquitin-conjugating enzyme.
  Mol Cell Biol, 21, 6537-6548.  
11182597 D.C.Swinney (2001).
Targeting protein ubiquitination for drug discovery. What is in the drug discovery toolbox?
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11722579 G.Martinez-Noel, U.Müller, and K.Harbers (2001).
Identification of molecular determinants required for interaction of ubiquitin-conjugating enzymes and RING finger proteins.
  Eur J Biochem, 268, 5912-5919.  
11313482 G.Wang, J.M.McCaffery, B.Wendland, S.Dupré, R.Haguenauer-Tsapis, and J.M.Huibregtse (2001).
Localization of the Rsp5p ubiquitin-protein ligase at multiple sites within the endocytic pathway.
  Mol Cell Biol, 21, 3564-3575.  
11410931 J.Myung, K.B.Kim, and C.M.Crews (2001).
The ubiquitin-proteasome pathway and proteasome inhibitors.
  Med Res Rev, 21, 245-273.  
11701647 R.D.Nicholls, and J.L.Knepper (2001).
Genome organization, function, and imprinting in Prader-Willi and Angelman syndromes.
  Annu Rev Genomics Hum Genet, 2, 153-175.  
10966114 N.Zheng, P.Wang, P.D.Jeffrey, and N.P.Pavletich (2000).
Structure of a c-Cbl-UbcH7 complex: RING domain function in ubiquitin-protein ligases.
  Cell, 102, 533-539.
PDB code: 1fbv
10998601 P.K.Jackson, A.G.Eldridge, E.Freed, L.Furstenthal, J.Y.Hsu, B.K.Kaiser, and J.D.Reimann (2000).
The lore of the RINGs: substrate recognition and catalysis by ubiquitin ligases.
  Trends Cell Biol, 10, 429-439.  
11027293 S.Nakagawa, and J.M.Huibregtse (2000).
Human scribble (Vartul) is targeted for ubiquitin-mediated degradation by the high-risk papillomavirus E6 proteins and the E6AP ubiquitin-protein ligase.
  Mol Cell Biol, 20, 8244-8253.  
10864652 W.H.Kao, S.L.Beaudenon, A.L.Talis, J.M.Huibregtse, and P.M.Howley (2000).
Human papillomavirus type 16 E6 induces self-ubiquitination of the E6AP ubiquitin-protein ligase.
  J Virol, 74, 6408-6417.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.