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498  structures 1575  species 0  interactions 47832  sequences 763  architectures

Family: UQ_con (PF00179)

Summary: Ubiquitin-conjugating enzyme

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This is the Wikipedia entry entitled "Ubiquitin-conjugating enzyme". More...

Ubiquitin-conjugating enzyme Edit Wikipedia article

Ubiquitin—protein ligase
EC number6.3.2.19
CAS number74812-49-0
IntEnzIntEnz view
ExPASyNiceZyme view
MetaCycmetabolic pathway
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Ubiquitin-conjugating enzyme, E2

Ubiquitin-conjugating enzymes, also known as E2 enzymes and more rarely as ubiquitin-carrier enzymes, perform the second step in the ubiquitination reaction that targets a protein for degradation via the proteasome. The ubiquitination process covalently attaches ubiquitin, a short protein of 76 amino acids, to a lysine residue on the target protein. Once a protein has been tagged with one ubiquitin molecule, additional rounds of ubiquitination form a polyubiquitin chain that is recognized by the proteasome's 19S regulatory particle, triggering the ATP-dependent unfolding of the target protein that allows passage into the proteasome's 20S core particle, where proteases degrade the target into short peptide fragments for recycling by the cell.


A ubiquitin-activating enzyme, or E1, first activates the ubiquitin by covalently attaching the molecule to its active site cysteine residue. The activated ubiquitin is then transferred to an E2 cysteine. Once conjugated to ubiquitin, the E2 molecule binds one of several ubiquitin ligases or E3s via a structurally conserved binding region. The E3 molecule is responsible for binding the target protein substrate and transferring the ubiquitin from the E2 cysteine to a lysine residue on the target protein.[1]

A particular cell usually contains only a few types of E1 molecule, a greater diversity of E2s, and a very large variety of E3s. The E3 molecules responsible for substrate identification and binding are thus the mechanisms of substrate specificity in proteasomal degradation. Each type of E2 can associate with many E3s.[2]


The following human genes encode ubiquitin-conjugating enzymes:

See also


  1. ^ Nandi D, Tahiliani P, Kumar A, Chandu D (2006). "The ubiquitin-proteasome system" (PDF). Journal of Biosciences. 31 (1): 137–55. doi:10.1007/BF02705243. PMID 16595883.
  2. ^ Risseeuw EP, Daskalchuk TE, Banks TW, Liu E, Cotelesage J, Hellmann H, Estelle M, Somers DE, Crosby WL (2003). "Protein interaction analysis of SCF ubiquitin E3 ligase subunits from Arabidopsis". The Plant Journal. 34 (6): 753–67. doi:10.1046/j.1365-313X.2003.01768.x. PMID 12795696.

External links

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Ubiquitin-conjugating enzyme Provide feedback

Proteins destined for proteasome-mediated degradation may be ubiquitinated. Ubiquitination follows conjugation of ubiquitin to a conserved cysteine residue of UBC homologues. TSG101 is one of several UBC homologues that lacks this active site cysteine [4, 5].

Literature references

  1. Cook WJ, Jeffrey LC, Sullivan ML, Vierstra RD; , J Biol Chem 1992;267:15116-15121.: Three-dimensional structure of a ubiquitin-conjugating enzyme (E2). PUBMED:1321826 EPMC:1321826

  2. Cook WJ, Jeffrey LC, Xu Y, Chau V; , Biochemistry 1993;32:13809-13817.: Tertiary structures of class I ubiquitin-conjugating enzymes are highly conserved: crystal structure of yeast Ubc4. PUBMED:8268156 EPMC:8268156

  3. Cook WJ, Martin PD, Edwards BF, Yamazaki RK, Chau V; , Biochemistry 1997;36:1621-1627.: Crystal structure of a class I ubiquitin conjugating enzyme (Ubc7) from Saccharomyces cerevisiae at 2.9 angstroms resolution. PUBMED:9048545 EPMC:9048545

  4. Koonin EV, Abagyan RA; , Nat Genet 1997;16:330-331.: TSG101 may be the prototype of a class of dominant negative ubiquitin regulators. PUBMED:9241264 EPMC:9241264

  5. Ponting CP, Cai YD, Bork P , J Mol Med 1997;75:467-469.: The breast cancer gene product TSG101: a regulator of ubiquitination? PUBMED:9253709 EPMC:9253709

  6. Burroughs AM, Jaffee M, Iyer LM, Aravind L;, J Struct Biol. 2008;162:205-218.: Anatomy of the E2 ligase fold: implications for enzymology and evolution of ubiquitin/Ub-like protein conjugation. PUBMED:18276160 EPMC:18276160

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000608

Ubiquitin-conjugating enzymes (UBC or E2 enzymes) [ PUBMED:2193438 , PUBMED:1647207 , PUBMED:1656558 ] catalyse the covalent attachment of ubiquitin to target proteins. Ubiquitinylation is an ATP-dependent process that involves the action of at least three enzymes: a ubiquitin-activating enzyme (E1, INTERPRO ), a ubiquitin-conjugating enzyme (E2), and a ubiquitin ligase (E3, INTERPRO , INTERPRO ), which work sequentially in a cascade [ PUBMED:14998368 ]. The E1 enzyme mediates an ATP-dependent transfer of a thioester-linked ubiquitin molecule to a cysteine residue on the E2 enzyme. The E2 enzyme ( EC ) then either transfers the ubiquitin moiety directly to a substrate, or to an E3 ligase, which can also ubiquitinylate a substrate.

There are several different E2 enzymes (over 30 in humans), which are broadly grouped into four classes, all of which have a core catalytic domain (containing the active site cysteine), and some of which have short N- and C-terminal amino acid extensions: class I enzymes consist of just the catalytic core domain (UBC), class II possess a UBC and a C-terminal extension, class III possess a UBC and an N-terminal extension, and class IV possess a UBC and both N- and C-terminal extensions. These extensions appear to be important for some subfamily function, including E2 localisation and protein-protein interactions [ PUBMED:15545318 ]. In addition, there are proteins with an E2-like fold that are devoid of catalytic activity (such as protein crossbronx from flies), but which appear to assist in poly-ubiquitin chain formation.

Domain organisation

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Pfam Clan

This family is a member of clan UBC (CL0208), which has the following description:

This superfamily includes a diverse set of proteins that bind to ubiquitin [1].

The clan contains the following 13 members:

FANCL_d1 FANCL_d2 FANCL_d3 Knl1_RWD_C Prok-E2_A Prok-E2_B Prok-E2_C Prok-E2_D Prok-E2_E RWD UEV UFC1 UQ_con


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Curation and family details

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Seed source: Prosite
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Ponting CP , Schultz J, Bork P , Finn RD
Number in seed: 64
Number in full: 47832
Average length of the domain: 131.60 aa
Average identity of full alignment: 28 %
Average coverage of the sequence by the domain: 43.41 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.3 21.3
Trusted cut-off 21.3 21.3
Noise cut-off 21.2 21.2
Model length: 140
Family (HMM) version: 28
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Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the UQ_con domain has been found. There are 498 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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