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270  structures 571  species 9  interactions 9194  sequences 127  architectures

Family: UQ_con (PF00179)

Summary: Ubiquitin-conjugating enzyme

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

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

Ubiquitin-conjugating enzyme Edit Wikipedia article

Ubiquitin—protein ligase
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 / EGO
Ubiquitin-conjugating enzyme, E2
Identifiers
Symbol UBQ-conjugat_E2
Pfam PF00179
InterPro IPR000608
SMART SM00212
PROSITE PDOC00163

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[edit]

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[edit]

The following human genes encode ubiquitin-conjugating enzymes:

See also[edit]

References[edit]

  1. ^ 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. 
  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 : for cell and molecular biology 34 (6): 753–67. doi:10.1046/j.1365-313X.2003.01768.x. PMID 12795696. 

External links[edit]


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.

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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

The post-translational attachment of ubiquitin (INTERPRO) to proteins (ubiquitinylation) alters the function, location or trafficking of a protein, or targets it to the 26S proteasome for degradation [PUBMED:15556404, PUBMED:15196553, PUBMED:15454246]. 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, but which appear to assist in poly-ubiquitin chain formation.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

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

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 9 members:

Prok-E2_A Prok-E2_B Prok-E2_C Prok-E2_D Prok-E2_E RWD UEV UFC1 UQ_con

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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

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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.

  Seed
(71)
Full
(9194)
Representative proteomes NCBI
(8415)
Meta
(316)
RP15
(1995)
RP35
(3131)
RP55
(4649)
RP75
(5880)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(71)
Full
(9194)
Representative proteomes NCBI
(8415)
Meta
(316)
RP15
(1995)
RP35
(3131)
RP55
(4649)
RP75
(5880)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

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.

  Seed
(71)
Full
(9194)
Representative proteomes NCBI
(8415)
Meta
(316)
RP15
(1995)
RP35
(3131)
RP55
(4649)
RP75
(5880)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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

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.

Note: You can also download the data file for the tree.

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 View help on the curation process

Seed source: Prosite
Previous IDs: none
Type: Domain
Author: Ponting CP, Schultz J, Bork P, Finn RD
Number in seed: 71
Number in full: 9194
Average length of the domain: 134.10 aa
Average identity of full alignment: 27 %
Average coverage of the sequence by the domain: 49.81 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -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 21.1 21.2
Model length: 140
Family (HMM) version: 21
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 9 interactions for this family. More...

ThiF Cbl_N2 ubiquitin U-box UQ_con HECT E2_bind zf-C3HC4 UBA

Structures

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 270 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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