Summary: Ubiquitin-conjugating enzyme
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Ubiquitin-conjugating enzyme Edit Wikipedia article
Ubiquitin—protein ligase | |||||||||
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Identifiers | |||||||||
EC number | 6.3.2.19 | ||||||||
CAS number | 74812-49-0 | ||||||||
Databases | |||||||||
IntEnz | IntEnz view | ||||||||
BRENDA | BRENDA entry | ||||||||
ExPASy | NiceZyme view | ||||||||
KEGG | KEGG entry | ||||||||
MetaCyc | metabolic pathway | ||||||||
PRIAM | profile | ||||||||
PDB structures | RCSB PDB PDBe PDBsum | ||||||||
Gene Ontology | AmiGO / QuickGO | ||||||||
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Ubiquitin-conjugating enzyme, E2 | |||||||||
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Identifiers | |||||||||
Symbol | UBQ-conjugat_E2 | ||||||||
Pfam | PF00179 | ||||||||
InterPro | IPR000608 | ||||||||
SMART | SM00212 | ||||||||
PROSITE | PDOC00163 | ||||||||
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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.
Relationships
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]
Isozymes
The following human genes encode ubiquitin-conjugating enzymes:
- UBE2A
- UBE2B
- UBE2C
- UBE2D1, UBE2D2, UBE2D3, UBE2D4 (the latter putative)
- UBE2E1, UBE2E2, UBE2E3
- UBE2F (putative)
- UBE2G1, UBE2G2
- UBE2H
- UBE2I
- UBE2J1, UBE2J2
- UBE2K
- UBE2L3, UBE2L6; (UBE2L1, UBE2L2, UBE2L4 are pseudogenes)
- UBE2M
- UBE2N
- UBE2O
- UBE2Q1, UBE2Q2
- UBE2R1 (CDC34), UBE2R2
- UBE2S
- UBE2T (putative)
- UBE2U (putative)
- UBE2V1, UBE2V2
- UBE2W (putative)
- UBE2Z
- ATG3
- BIRC6
- UFC1
See also
References
- ^ Nandi D, Tahiliani P, Kumar A, Chandu D (2006). "The ubiquitin-proteasome system". Journal of biosciences. 31 (1): 137–55. PMID 16595883. doi:10.1007/BF02705243.
- ^ 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. PMID 12795696. doi:10.1046/j.1365-313X.2003.01768.x.
External links
- Eukaryotic Linear Motif resource motif class MOD_SUMO
- Ubiquitin-Conjugating Enzymes at the US National Library of Medicine Medical Subject Headings (MeSH)
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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
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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
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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
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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
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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
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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
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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: | Prok-E2_B RWD UEV UFC1 |
Similarity to PfamA using HHSearch: | UEV UFC1 Prok-E2_B |
External database links
HOMSTRAD: | uce |
PROSITE: | PDOC00163 |
SCOP: | 1aak |
SMART: | UBCc |
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
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
Alignments
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...
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Seed (65) |
Full (30654) |
Representative proteomes | UniProt (44040) |
NCBI (46265) |
Meta (315) |
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RP15 (8243) |
RP35 (16631) |
RP55 (24020) |
RP75 (29325) |
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PP/heatmap | 1 |
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
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Seed (65) |
Full (30654) |
Representative proteomes | UniProt (44040) |
NCBI (46265) |
Meta (315) |
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RP15 (8243) |
RP35 (16631) |
RP55 (24020) |
RP75 (29325) |
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Raw Stockholm | |||||||||
Gzipped |
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logo
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
Trees
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Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
Seed source: | Prosite |
Previous IDs: | none |
Type: | Domain |
Sequence Ontology: | SO:0000417 |
Author: |
Ponting CP |
Number in seed: | 65 |
Number in full: | 30654 |
Average length of the domain: | 132.40 aa |
Average identity of full alignment: | 27 % |
Average coverage of the sequence by the domain: | 43.74 % |
HMM information
HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
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Model details: |
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Model length: | 140 | ||||||||||||
Family (HMM) version: | 26 | ||||||||||||
Download: | download the raw HMM for this family |
Species distribution
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Interactions
There are 35 interactions for this family. More...
Peroxin-22 zf-C3HC4_2 E1_UFD UBA_e1_thiolCys Rad60-SLD SopA_C ubiquitin Cbl_N2 IBN_N Xpo1 Rad60-SLD zf-A20 UBA SopA RanGAP1_C UBA ubiquitin HECT zf-RING_2 zf-C3HC4_3 HECT zf-RING_4 Peptidase_C65 zf-C3HC4 Peptidase_C65 zf-RING_2 UQ_con zf-C3HC4_3 U-box E2_bind zf-C3HC4 ThiF E2_bind IR1-M RanGAP1_CStructures
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 411 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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