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Information on EC 2.3.2.23 - E2 ubiquitin-conjugating enzyme and Organism(s) Saccharomyces cerevisiae and UniProt Accession P29340
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2.3.2.23 E2 ubiquitin-conjugating enzymeIUBMB Comments
The E2 ubiquitin-conjugating enzyme acquires the activated ubquitin from the E1 ubiquitin-activating enzyme (EC 6.2.1.45) and binds it via a transthioesterification reaction to itself. In the human enzyme the catalytic center is located at Cys-87 where ubiquitin is bound via its C-terminal glycine in a thioester linkage.
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Word Map
- 2.3.2.23
- proteasome
- ligases
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polyubiquitination
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sumoylation
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ubiquitin-like
- finger
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ubiquitin-proteasome
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ubiquitylation
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monoubiquitination
- ubiquitin-protein
-
ubiquitin-activating
-
k63-linked
-
ubiquitin-dependent
-
cullins
- parkin
-
ubiquitin-mediated
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ubiquitin-related
-
fanconi
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anaphase-promoting
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deubiquitinating
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cullin-ring
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isopeptide
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error-free
- isg15
-
lys63-linked
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neddylation
- cdc20
- sumo1
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autoubiquitination
- traf6
-
er-associated
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ring-h2
- ranbp2
- tak1
- thiolester
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ring-finger
- sic1
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e3-ligase
-
multiubiquitination
- tpx2
- rbx1
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translesion
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fancd2
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aurka
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postreplication
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conjugase
-
ubiquitin-binding
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ubiquitin-ligase
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ring-type
- medicine
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nonerythroid
- diagnostics
- drug development
The taxonomic range for the selected organisms is: Saccharomyces cerevisiae
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
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S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
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[E2 ubiquitin-conjugating enzyme]-L-cysteine
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[E1 ubiquitin-activating enzyme]-L-cysteine
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S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine
Synonyms
ube2c, cdc34, ubc13, ube2t, ubch10, e2 enzyme, ube2s, ubch7, e2 ubiquitin-conjugating enzyme, ube2l3, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
PATHWAY SOURCE
PATHWAYS
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SYSTEMATIC NAME
IUBMB Comments
S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine:[E2 ubiquitin-conjugating enzyme] ubiquitinyl transferase
The E2 ubiquitin-conjugating enzyme acquires the activated ubquitin from the E1 ubiquitin-activating enzyme (EC 6.2.1.45) and binds it via a transthioesterification reaction to itself. In the human enzyme the catalytic center is located at Cys-87 where ubiquitin is bound via its C-terminal glycine in a thioester linkage.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine
[E1 ubiquitin-activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine
S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine
[E1 ubiquitin-activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine
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-
-
-
?
S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine
[E1 ubiquitin-activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine
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-
-
?
S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine
[E1 ubiquitin-activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine
the E2 ubiquitin-conjugating enzyme acquires the activated ubquitin from the E1 ubiquitin-activating enzyme
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-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine
[E1 ubiquitin-activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine
S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine
[E1 ubiquitin-activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine
-
-
-
-
?
S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine
[E1 ubiquitin-activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine
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?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
the ubiquitin-like modifier-activating enzyme 1 (Uba1, EC 6.2.1.45) is a multidomain enzyme that serves as the gatekeeper of the ubiquitin (Ub) conjugation cascade by activating Ub in a two-step process involving adenylation and thioester bond formation followed by transfer of Ub to E2s in a process termed E1-E2 thioester transfer or transthiolation. Cdc34 is one of tens of E2s that must function with Uba1 despite significant differences at their predicted UFD-interacting surfaces. Molecular recognition of Cdc34 by Uba1, overview. Analysis with Uba1 from Homo sapiens, Saccharomyces cerevisiae, and Schizosaccharomyces pombe
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
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knockdown of enzyme expression in decreases tombusvirus accumulation and reduces symptom severity
metabolism
the ubiquitin-like modifier-activating enzyme 1 (Uba1, EC 6.2.1.45) is a multidomain enzyme that serves as the gatekeeper of the ubiquitin (Ub) conjugation cascade by activating Ub in a two-step process involving adenylation and thioester bond formation followed by transfer of Ub to E2s in a process termed E1-E2 thioester transfer or transthiolation. Cdc34 is one of tens of E2s that must function with Uba1 despite significant differences at their predicted UFD-interacting surfaces. Molecular recognition of Cdc34 by Uba1, overview
physiological function
additional information
analyis of the molecular basis by which Cdc34 engages its E1, and the structural mechanisms, by which its unique C-terminal extension functions in Cdc34 activity. Conformational changes in Uba1 and Cdc34 and a unique binding mode are required for transthiolation. The Cdc34-Ub structure reveals contacts between the Cdc34 C-terminal extension and Ub that stabilize Cdc34-Ub in a closed conformation and are critical for Ub discharge
physiological function
residues within helix alpha2 of Ubc7 that interact with donor ubiquitin are essential for polyubiquitin conjugation by Ubc7 and its cognate E3 enzymes. Mutagenesis of these residues inhibits the in vitro activity of Ubc7 by preventing the conjugation of donor ubiquitin to the acceptor. Ubiquitin chain formation by mutant Ubc7 is restored selectively by the E3 enzyme Hrd1 RING domain but not by the E3 enzyme Doa10 RING domain. alpha2 Helix mutations selectively impair the in vivo degradation of Doa10 substrates but have no apparent effect on the degradation of Hrd1 substrates
physiological function
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the enzyme is critical for tombvirus replication and is involved in promoting the subversion of Vps23p and Vps4p ESCRT proteins for viral replicase complex assembly
physiological function
ubiquitin (Ub) signaling requires the sequential interactions and activities of three enzymes, E1, E2, and E3. Cdc34 is an E2 that plays a key role in regulating cell cycle progression and requires unique structural elements to function, molecular mechanisms by which Cdc34 function in cells, overview. An ordered Cdc34 CTDprox extension is involved in Ub discharge, CTDprox/Ub contacts are important for Cdc34 action in cells. Cdc34 CTDprox locks Ub(t) in the closed conformation. The Cdc34 CTDprox extension is involved in Ub discharge
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
isoform Pex4 can form a disulfide bond between the cysteine residues at positions 105 and 146. Mutating the disulfide forming cysteine residues to serines does not disturb the secondary structure of the protein but does reduce the in vitro activity of Pex4. Structure of mutant C105S/C146S in complex with the soluble domain of peroxisomal membrane protein Pex22 shows a narrowing of the active site cleft, caused by loss of the disulfide bond. This modification of the active site microenvironment is likely to restrict access of ubiquitin to the active site cysteine, modulating Pex4 activity
additional information
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isoform Pex4 can form a disulfide bond between the cysteine residues at positions 105 and 146. Mutating the disulfide forming cysteine residues to serines does not disturb the secondary structure of the protein but does reduce the in vitro activity of Pex4. Structure of mutant C105S/C146S in complex with the soluble domain of peroxisomal membrane protein Pex22 shows a narrowing of the active site cleft, caused by loss of the disulfide bond. This modification of the active site microenvironment is likely to restrict access of ubiquitin to the active site cysteine, modulating Pex4 activity
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
mutant C105S/C146S in complex with the soluble domain of peroxisomal membrane protein Pex22. Structure shows a narrowing of the active site cleft, caused by loss of the disulfide bond
Cdc34 alone and in complex with E1, and a Cdc34-Ub thioester mimetic representing the product of Uba1-Cdc34 Ub transthiolation, sitting drop method, mixing of 200 nl of 8.7 mg/ml Uba1-Cdc34DELTAdist crosslink and 0.116 mM Ub, 1 mM ATP, and 5 mM MgCl2, with 200 nl of mother liquor containing 0.2 M ammonium sulfate, 25% PEG 3,350, 0.1 M Bis-Tris, pH 6.5, 18°C, for the free Cdc34DELTAdist, hanging drop method is used with 10 mg/ml protein and mother liquor containing 0.06 M zinc acetate, 0.108 M sodium cacodylate, 14.4% PEG 8000, and 20% glycerol, 18°C, a 1.3fold excess of Cdc34 inhibitor CC0651 is used as a crystallization aid, X-ray diffraction structure determination and analysis at 1.65-2.07 A resolution, molecular replacement using structure PDB ID 3CMM as the search model, modeling
crystal structures of the C-terminal ubiquitin fold domain from yeast Uba2 alone and in complex with E2 enzyme Ubc9. Uba2 undergoes remarkable conformational changes during the reaction. The structure of the Uba2 domain-Ubc9 complex reveals interactions unique to Sumo E1 and E2. Comparison with a previous Ubc9-E3 complex structure demonstrates overlap between Uba2 and E3 binding sites on Ubc9, indicating that loading with Sumo and E3-catalyzed transfer to substrates are strictly separate steps
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C105S/C146S
mutation of the residues forming an intramolecular disulfide bond. Mutation does not disturb the secondary structure of the protein but does reduce the in vitro activity of isoform Pex4
K118R
residue Lys118 is required for Ubc7 activity. Mutant is very poor in assembly of polyubiquitin chains. Lys118 is both essential and sufficient for Doa10-mediated degradation of substrates
additional information
generation of a Cdc34 active site Cys to Lys mutant
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged enzyme from Escherichia coli strain BL21 (DE3) Codon Plus by nickel affinity chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene cdc34, recombinant His-tagged enzyme expression in Escherichia coli strain BL21 (DE3) Codon Plus
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Wang, J.; Taherbhoy, A.M.; Hunt, H.W.; Seyedin, S.N.; Miller, D.W., Miller, D.J.; Huang, D.T.; Schulman, B.A.
Crystal structure of UBA2ufd-Ubc9: Insights into E1-E2 interactions in Sumo pathways
PLoS ONE
1
e15805
2010
Saccharomyces cerevisiae (P50623), Saccharomyces cerevisiae
Cohen, I.; Wiener, R.; Reiss, Y.; Ravid, T.
Distinct activation of an E2 ubiquitin-conjugating enzyme by its cognate E3 ligases
Proc. Natl. Acad. Sci. USA
112
E625-E632
2015
Saccharomyces cerevisiae (Q02159), Saccharomyces cerevisiae
Williams, C.; Van Den Berg, M.; Stanley, W.; Wilmanns, M.; Distel, B.
A disulphide bond in the E2 enzyme Pex4p modulates ubiquitin-conjugating activity
Sci. Rep.
3
2212
2013
Saccharomyces cerevisiae (P29340), Saccharomyces cerevisiae
Imura, Y.; Molho, M.; Chuang, C.; Nagy, P.D.
Cellular Ubc2/Rad6 E2 ubiquitin-conjugating enzyme facilitates tombusvirus replication in yeast and plants
Virology
484
265-275
2015
Arabidopsis thaliana, Saccharomyces cerevisiae, Saccharomyces cerevisiae BY4741
Williams, K.M.; Qie, S.; Atkison, J.H.; Salazar-Arango, S.; Alan Diehl, J.; Olsen, S.K.
Structural insights into E1 recognition and the ubiquitin-conjugating activity of the E2 enzyme Cdc34
Nat. Commun.
10
3296
2019
Saccharomyces cerevisiae (P14682), Homo sapiens (P49427), Saccharomyces cerevisiae ATCC 204508 (P14682)
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