UBCcUbiquitin-conjugating enzyme E2, catalytic domain homologues
|SMART accession number:||SM00212|
|Description:||Proteins destined for proteasome-mediated degradation may be ubiquitinated. Ubiquitination follows conjugation of ubiquitin to a conserved cysteine residue of UBC homologues. This pathway functions in regulating many fundamental processes required for cell viability.TSG101 is one of several UBC homologues that lacks this active site cysteine.|
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- Evolution (species in which this domain is found)
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This tree shows only several representative species. The complete taxonomic breakdown of all proteins with UBCc domain is also avaliable.
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Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes
- Cellular role (predicted cellular role)
Binding / catalysis: protein-binding, ubiquitin-conjugating
- Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Cook WJ, Martin PD, Edwards BF, Yamazaki RK, Chau V
- Crystal structure of a class I ubiquitin conjugating enzyme (Ubc7) from Saccharomyces cerevisiae at 2.9 angstroms resolution.
- Biochemistry. 1997; 36: 1621-7
- Display abstract
Ubiquitin-conjugating enzymes are a family of related proteins that participate in the ubiquitination of proteins. Previous studies on the crystal structures of Saccharomyces cerevisiae Ubc4 and Arabidopsis thaliana Ubc1 indicated that the smallest enzymes (class I), which consist entirely of the conserved core domain, share a common tertiary fold. Here we report the three-dimensional structure of the S. cerevisiae class I enzyme encoded by the UBC7 gene. The crystal structure has been solved using molecular replacement techniques and refined by simulated annealing to an R-factor of 0.183 at 2.93 A resolution. Bond lengths and angles in the molecule have root-mean-square deviations from ideal values of 0.016 A and 2.3 degrees, respectively. Ubc7 is an alpha/beta protein with four alpha-helices and a four-stranded antiparallel beta-sheet. With the exception of two regions where extra residues are present, the tertiary folding of Ubc7 is similar to those of the other two enzymes. The ubiquitin-accepting cysteine is located in a cleft between two loops. One of these loops is nonconserved, as this region of the Ubc7 molecule differs from the other two enzymes by having 13 extra residues. There is also a second single amino acid insertion that alters the orientation of the turn between the first two beta-strands. Analysis of the 13 ubiquitin-conjugating enzyme sequences in S. cerevisiae indicates that there may be two other regions where extra residues could be inserted into the common tertiary fold. Both of these other regions exhibit significant deviations in the superposition of the three structures and, like the two insertion regions in Ubc7, may represent hypervariable regions within a common tertiary fold. As ubiquitin-conjugating enzymes interact with different substrates or other accessory proteins in the ubiquitination pathway, these variable surface regions may confer distinct specificity to individual enzymes.
- Hatakeyama S, Jensen JP, Weissman AM
- Subcellular localization and ubiquitin-conjugating enzyme (E2) interactions of mammalian HECT family ubiquitin protein ligases.
- J Biol Chem. 1997; 272: 15085-92
- Display abstract
In most instances, the transfer of ubiquitin to target proteins is catalyzed by the action of ubiquitin protein ligases (E3s). Full-length cDNAs encoding murine E6-associated protein (mE6-AP) as well as Nedd-4, a protein that is homologous to E6-AP in its C terminus, were cloned. Nedd-4 and mouse E6-AP are both enzymatically active E3s and function with members of the UbcH5 family of E2s. Mouse E6-AP, like its human counterpart, ubiquitinates p53 in the presence of human papilloma virus E6 protein, while Nedd-4 does not. Consistent with its role in p53 ubiquitination, mE6-AP was found both in the nucleus and cytosol, while Nedd-4 was found only in the cytosol. Binding studies implicate a 150-amino acid region that is 40% identical between mE6-AP and Nedd-4 as a binding site for the C-terminal portion of an E2 enzyme (UbcH5B). Nedd-4 was determined to have a second nonoverlapping E2 binding site that recognizes the first 67 amino acids of UbcH5B but not the more C-terminal portion of this E2. These findings provide the first demonstration of physical interactions between mammalian E2s and E3s and establish that these interactions occur independently of ubiquitin and an intact E3 catalytic domain. Furthermore, the presence of two E2 binding sites within Nedd-4 suggests models for ubiquitination involving multiple E2 enzymes associated with E3s.
- Koonin EV, Abagyan RA
- TSG101 may be the prototype of a class of dominant negative ubiquitin regulators.
- Nat Genet. 1997; 16: 330-1
- Kumar S, Kao WH, Howley PM
- Physical interaction between specific E2 and Hect E3 enzymes determines functional cooperativity.
- J Biol Chem. 1997; 272: 13548-54
- Display abstract
The cellular protein E6AP functions as an E3 ubiquitin protein ligase in the E6-dependent ubiquitination of p53. E6AP is a member of a family of functionally related E3 proteins that share a conserved carboxyl-terminal region called the Hect domain. Although several different E2 ubiquitin-conjugating enzymes have been shown to function with E6AP in the E6-dependent ubiquitination of p53 in vitro, the E2s that cooperate with E6AP in the ubiquitination of its normal substrates are presently unknown. Moreover, the basis of functional cooperativity between specific E2 and Hect E3 proteins has not yet been determined. Here we report the cloning of a new human E2, designated UbcH8, that was identified in a two-hybrid screen through specific interaction with E6AP. We demonstrate that UbcH7, an E2 closely related to UbcH8, can also bind to E6AP. The region of E6AP involved in complex formation with UbcH8 and UbcH7 was mapped to its Hect domain. Furthermore, we show that UbcH5 and UbcH6, two highly homologous E2s that were deficient for interaction with E6AP, could associate efficiently with another Hect-E3 protein, RSP5. Finally, only the E6AP-interacting E2s could function in conjunction with E6AP in the ubiquitination of an E6 independent substrate of E6AP, whereas the noninteracting E2s could not. Taken together, these studies demonstrate for the first time complex formation between specific human E2s and the Hect domain family of E3 proteins and suggest that selective physical interaction between E2 and E3 enzymes forms the basis of specificity for functionally distinct E2:E3 combinations.
- Ponting CP, Aravind L
- PAS: a multifunctional domain family comes to light.
- Curr Biol. 1997; 7: 6747-6747
- Ponting CP, Cai YD, Bork P
- The breast cancer gene product TSG101: a regulator of ubiquitination?
- J Mol Med. 1997; 75: 467-9
- Display abstract
Sequence analysis is a powerful tool to obtain structural and functional information about genes and their products. Here we show that TSG101, a gene subjected to somatic mutations in breast cancer, contains an amino terminal domain that is a homologue of ubiquitin conjugating enzymes (UBCs) and not, as previously proposed, DNA-binding domains. As the UBC active site residue is replaced in the TSG101 sequence in a similar manner to several other members of the UBC family, we propose a role for TSG101 in regulating the ubiquitination of short-lived gene products.
- Cook WJ, Jeffrey LC, Xu Y, Chau V
- Tertiary structures of class I ubiquitin-conjugating enzymes are highly conserved: crystal structure of yeast Ubc4.
- Biochemistry. 1993; 32: 13809-17
- Display abstract
The three-dimensional structure of a yeast ubiquitin-conjugating enzyme, encoded by the Saccharomyces cerevisiae UBC4 gene, has been determined at 2.7 A. The structure was solved using molecular replacement techniques and refined by simulated annealing to an R-factor of 0.198. Bond lengths and angles in the molecule have root mean square deviations from ideal values of 0.018 A and 4.0 degrees, respectively. Ubc4 is an alpha/beta protein with four alpha-helices and a four-stranded antiparallel beta-sheet. The ubiquitin-accepting cysteine is located in a cleft between two loops. Comparison with the recently determined structure of a different plant enzyme suggests that class I ubiquitin-conjugating enzymes are highly conserved in their three-dimensional folding. Except for two extra residues at the N- and the C-terminus of the plant enzyme, the C alpha atoms of the two enzymes can be superimposed with a root mean square deviation of only 1.52 A. Greater variations are found between the surfaces of the two molecules, as most of the identical residues between the two enzymes are either buried or clustered on the surface that lies adjacent to the ubiquitin-accepting cysteine. We suggest that this conserved surface functions in protein-protein binding during ubiquitin thiol ester formation.
- Cook WJ, Jeffrey LC, Sullivan ML, Vierstra RD
- Three-dimensional structure of a ubiquitin-conjugating enzyme (E2).
- J Biol Chem. 1992; 267: 15116-21
- Display abstract
The x-ray crystal structure of a recombinant ubiquitin-conjugating enzyme (E2) encoded by the UBC1 gene of the plant Arabidopsis thaliana has been determined with the use of multiple isomorphous replacement techniques and refined at 2.4-A resolution by simulated annealing and restrained least-squares. This E2 is an alpha/beta protein, with four alpha-helices and a four-stranded antiparallel beta-sheet. The NH2 and COOH termini, which may be important for interaction with other enzymes and substrates in the ubiquitin-conjugation pathway, are on the opposite side of the molecule from the cysteine residue that binds to the COOH terminus of ubiquitin. This structure should now allow for the rational analysis of E2 function by in vitro mutagenesis and facilitate the effective design of E2s with unique specificities or catalytic functions.
- Metabolism (metabolic pathways involving proteins which contain this domain)
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% proteins involved KEGG pathway ID Description 75.69 map04120 Ubiquitin mediated proteolysis 20.41 map05020 Parkinson's disease 3.67 map05040 Huntington's disease 0.23 map00380 Tryptophan metabolism
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with UBCc domain which could be assigned to a KEGG orthologous group, and not all proteins containing UBCc domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
- Structure (3D structures containing this domain)
3D Structures of UBCc domains in PDB
PDB code Main view Title 1a3s Human ubc9 1ayz Crystal structure of the saccharomyces cerevisiae ubiquitin- conjugating enzyme rad6 (ubc2) at 2.6a resolution 1c4z Structure of e6ap: insights into ubiquitination pathway 1fbv Structure of a cbl-ubch7 complex: ring domain function in ubiquitin-protein ligases 1fxt Structure of a conjugating enzyme-ubiquitin thiolester complex 1fzy Crystal structure of saccharomyces cerevisiae ubiquitin conjugating enzyme 1 1i7k Crystal structure of human mitotic-specific ubiquitin- conjugating enzyme, ubch10 1j74 Crystal structure of mms2 1j7d Crystal structure of hmms2-hubc13 1jas Hsubc2b 1jat Mms2/ubc13 ubiquitin conjugating enzyme complex 1jbb Ubiquitin conjugating enzyme, ubc13 1kpp Structure of the tsg101 uev domain 1kpq Structure of the tsg101 uev domain 1kps Structural basis for e2-mediated sumo conjugation revealed by a complex between ubiquitin conjugating enzyme ubc9 and rangap1 1m4p Structure of the tsg101 uev domain in complex with a hiv-1 ptap "late domain" peptide, dyana ensemble 1m4q Structure of the tsg101 uev domain in complex with a hiv-1 ptap "late domain" peptide, cns ensemble 1pzv Crystal structures of two ubc (e2) enzymes of the ubiquitin- conjugating system in caenorhabditis elegans 1q34 Crystal structures of two ubc (e2) enzymes of the ubiquitin- conjugating system in caenorhabditis elegans 1qcq Ubiquitin conjugating enzyme 1s1q Tsg101(uev) domain in complex with ubiquitin 1tte The structure of a class ii ubiquitin-conjugating enzyme, ubc1. 1u9a Human ubiquitin-conjugating enzyme ubc9 1u9b Murine/human ubiquitin-conjugating enzyme ubc9 1ur6 Nmr based structural model of the ubch5b-cnot4 complex 1uzx A complex of the vps23 uev with ubiquitin 1w4u Nmr solution structure of the ubiquitin conjugating enzyme ubch5b 1wzv Crystal structure of ubch8 1wzw Crystal structure of ubch8 1x23 Crystal structure of ubch5c 1y6l Human ubiquitin conjugating enzyme e2e2 1y8x Structural basis for recruitment of ubc12 by an e2-binding domain in nedd8's e1 1yf9 Structural analysis of leishmania major ubiquitin conjugating enzyme e2 1yh2 Ubiquitin-conjugating enzyme hspc150 1yla Ubiquitin-conjugating enzyme e2-25 kda (huntington interacting protein 2) 1yrv Novel ubiquitin-conjugating enzyme 1z2u The 1.1a crystallographic structure of ubiquitin- conjugating enzyme (ubc-2) from caenorhabditis elegans: functional and evolutionary significance 1z3d Protein crystal growth improvement leading to the 2.5a crystallographic structure of ubiquitin-conjugating enzyme (ubc-1) from caenorhabditis elegans 1z5s Crystal structure of a complex between ubc9, sumo-1, rangap1 and nup358/ranbp2 1zdn Ubiquitin-conjugating enzyme e2s 1zgu Solution structure of the human mms2-ubiquitin complex 1zuo Structure of human ubiquitin-conjugating enzyme (ubci) involved in embryo attachment and implantation 2a4d Structure of the human ubiquitin-conjugating enzyme e2 variant 1 (uev-1) 2a7l Structure of the human hypothetical ubiquitin-conjugating enzyme, loc55284 2aak Ubiquitin conjugating enzyme from arabidopsis thaliana 2awf Structure of human ubiquitin-conjugating enzyme e2 g1 2ayv Crystal structure of a putative ubiquitin-conjugating enzyme e2 from toxoplasma gondii 2bep Crystal structure of ubiquitin conjugating enzyme e2-25k 2bf8 Crystal structure of sumo modified ubiquitin conjugating enzyme e2-25k 2c2v Crystal structure of the chip-ubc13-uev1a complex 2c4o Crystal structure of human ubiquitin-conjugating enzyme ubch5b 2c4p Crystal structure of human ubiquitin-conjugating enzyme ubch5a 2clw Crystal structure of human ubiquitin-conjugating enzyme ubch5b 2cyx Structure of human ubiquitin-conjugating enzyme e2 g2 (ube2g2/ubc7) 2e2c E2-c, an ubiquitin conjugating enzyme required for the destruction of mitotic cyclins 2edi Solution structure of the uq_con domain from human nedd8- conjugating enzyme nce2 2eke Structure of a sumo-binding-motif mimic bound to smt3p- ubc9p: conservation of a noncovalent ubiquitin-like protein-e2 complex as a platform for selective interactions within a sumo pathway 2esk Human ubiquitin-conjugating enzyme (e2) ubch5b, wild-type 2eso Human ubiquitin-conjugating enzyme (e2) ubch5b mutant ile37ala 2esp Human ubiquitin-conjugating enzyme (e2) ubch5b mutant ile88ala 2esq Human ubiquitin-conjugating enzyme (e2) ubch5b mutant ser94gly 2f0r Crystallographic structure of human tsg101 uev domain 2f4w Human ubiquitin-conjugating enzyme e2 j2 2f4z Toxoplasma gondii ubiquitin conjugating enzyme tgtwinscan_2721- e2 domain 2fo3 Plasmodium vivax ubiquitin conjugating enzyme e2 2fuh Solution structure of the ubch5c/ub non-covalent complex 2gjd Distinct functional domains of ubc9 dictate cell survival and resistance to genotoxic stress 2gmi Mms2/ubc13~ubiquitin 2grn Crystal structure of human rangap1-ubc9 2gro Crystal structure of human rangap1-ubc9-n85q 2grp Crystal structure of human rangap1-ubc9-y87a 2grq Crystal structure of human rangap1-ubc9-d127a 2grr Crystal structure of human rangap1-ubc9-d127s 2h2y Crystal structure of ubiquitin conjugating enzyme e2 from plasmodium falciparum 2hlw Solution structure of the human ubiquitin-conjugating enzyme variant uev1a 2nvu Structure of appbp1-uba3~nedd8-nedd8-mgatp-ubc12(c111a), a trapped ubiquitin-like protein activation complex 2o25 Ubiquitin-conjugating enzyme e2-25 kda complexed with sumo- 1-conjugating enzyme ubc9 2ob4 Human ubiquitin-conjugating enzyme cdc34 2onu Plasmodium falciparum ubiquitin conjugating enzyme pf10_0330, putative homologue of human ube2h 2oxq Structure of the ubch5 :chip u-box complex 2pe6 Non-covalent complex between human sumo-1 and human ubc9 2pwq Crystal structure of a putative ubiquitin conjugating enzyme from plasmodium yoelii 2px9 The intrinsic affinity between e2 and the cys domain of e1 in ubiquitin-like modifications 2q0v Crystal structure of ubiquitin conjugating enzyme e2, putative, from plasmodium falciparum 2qgx Ubiquitin-conjugating enzyme e2q 2r0j Crystal structure of the putative ubiquitin conjugating enzyme, pfe1350c, from plasmodium falciparum 2ucz Ubiquitin conjugating enzyme (ubc7) from saccharomyces cerevisiae 2uyz Non-covalent complex between ubc9 and sumo1 2vrr Structure of sumo modified ubc9 2z5d Human ubiquitin-conjugating enzyme e2 h 3a33 Ubiquitin related protein 3bzh Crystal structure of human ubiquitin-conjugating enzyme e2 e1 3ceg Crystal structure of the ubc domain of baculoviral iap repeat-containing protein 6 3e46 Crystal structure of ubiquitin-conjugating enzyme e2-25kda (huntington interacting protein 2) m172a mutant 3e95 Crystal structure of the plasmodium falciparum ubiquitin conjugating enzyme complex, pfubc13-pfuev1a 3eb6 Structure of the ciap2 ring domain bound to ubch5b 3f92 Crystal structure of ubiquitin-conjugating enzyme e2-25kda (huntington interacting protein 2) m172a mutant crystallized at ph 8.5 3fn1 E2-ring expansion of the nedd8 cascade confers specificity to cullin modification. 3fsh Crystal structure of the ubiquitin conjugating enzyme ube2g2 bound to the g2br domain of ubiquitin ligase gp78 3h8k Crystal structure of ube2g2 complxed with the g2br domain of gp78 at 1.8-a resolution 3hct Crystal structure of traf6 in complex with ubc13 in the p1 space group 3hcu Crystal structure of traf6 in complex with ubc13 in the c2 space group
- Links (links to other resources describing this domain)
BLOCKS UBIQUITIN_CONJUGAT PFAM UQ_con