Summary: Ubiquitin-conjugating enzyme
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Ubiquitin-conjugating enzyme Edit Wikipedia article
|PDB structures||RCSB PDB PDBe PDBsum|
|Gene Ontology||AmiGO / EGO|
|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.
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.
The following human genes encode ubiquitin-conjugating enzymes:
- UBE2D1, UBE2D2, UBE2D3, UBE2D4 (the latter putative)
- UBE2E1, UBE2E2, UBE2E3
- UBE2F (putative)
- UBE2G1, UBE2G2
- UBE2J1, UBE2J2
- UBE2L3, UBE2L6; (UBE2L1, UBE2L2, UBE2L4 are pseudogenes)
- UBE2Q1, UBE2Q2
- UBE2R1 (CDC34), UBE2R2
- UBE2T (putative)
- UBE2U (putative)
- UBE2V1, UBE2V2
- UBE2W (putative)
- Nandi D, Tahiliani P, Kumar A, Chandu D (2006). "The ubiquitin-proteasome system". Journal of biosciences 31 (1): 137–55. doi:10.1007/BF02705243. PMID 16595883.
- 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 : for cell and molecular biology 34 (6): 753–67. doi:10.1046/j.1365-313X.2003.01768.x. PMID 12795696.
- Eukaryotic Linear Motif resource motif class MOD_SUMO
- Ubiquitin-Conjugating Enzymes at the US National Library of Medicine Medical Subject Headings (MeSH)
|This enzyme-related article is a stub. You can help Wikipedia by expanding it.|
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].
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
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
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
|SCOOP:||UEV RWD BRE UFC1 Prok-E2_A Prok-E2_B|
|Similarity to PfamA using HHSearch:||UEV UFC1 Prok-E2_B|
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.
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
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We make a range of alignments for each Pfam-A family:
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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
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|Author:||Ponting CP, Schultz J, Bork P, Finn RD|
|Number in seed:||65|
|Number in full:||16338|
|Average length of the domain:||132.90 aa|
|Average identity of full alignment:||28 %|
|Average coverage of the sequence by the domain:||46.74 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 17690987 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||24|
|Download:||download the raw HMM for this family|
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The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
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Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
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Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
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The tree shows the occurrence of this domain across different species. More...
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For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
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There are 35 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
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 354 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 seqence.
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