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Information on EC 6.2.1.45 - E1 ubiquitin-activating enzyme
for references in articles please use BRENDA:EC6.2.1.45
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EC Tree 6 Ligases
6.2 Forming carbon-sulfur bonds
6.2.1 Acid-thiol ligases
6.2.1.45 E1 ubiquitin-activating enzyme
IUBMB Comments
Catalyses the ATP-dependent activation of ubiquitin through the formation of a thioester bond between the C-terminal glycine of ubiquitin and the sulfhydryl side group of a cysteine residue in the E1 protein. The two-step reaction consists of the ATP-dependent formation of an E1-ubiquitin adenylate intermediate in which the C-terminal glycine of ubiquitin is bound to AMP via an acyl-phosphate linkage, then followed by the conversion to an E1-ubiquitin thioester bond via the cysteine residue on E1 in the second step.
The enzyme appears in viruses and cellular organisms
- 6.2.1.45
- proteasome
-
ubiquitin-proteasome
-
polyubiquitination
- ligases
- ubiquitin-protein
- finger
-
ubiquitin-dependent
-
sumoylation
- isg15
- cdc34
- rad6
-
isgylation
-
ubiquitin-mediated
-
deubiquitinating
-
anaphase-promoting
-
genorm
-
ubiquitin-related
- ubch7
-
normfinder
-
multiubiquitination
- sumo-1
-
nonpermissive
-
proteasome-dependent
-
cullins
- lactacystin
-
bestkeeper
-
ub-conjugating
- thiolester
- nedd8
-
postreplication
-
interferon-stimulated
- peroxins
-
ubiquitin-ligase
-
ring-h2
-
lys63-linked
-
mono-ubiquitination
-
error-free
- sic1
- drug development
- ube2l3
-
translesion
- synthesis
-
cullin-ring
- medicine
Reaction Schemes
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[E1 ubiquitin-activating enzyme]-L-cysteine
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S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
Synonyms
ubiquitin-conjugating enzyme, ube1l, ubiquitin-activating enzyme, ubiquitin-activating enzyme e1, ubiquitin-activating enzyme (e1), ubiquitin activating enzyme, sumo e1, e1 ubiquitin-activating enzyme, ubiquitin e1, ubiquitin activating enzyme e1, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
E1
E1 ubiquitin-activating enzyme
Uba1
Uba1/E1
UBA2
UBE1
UBE1L2
ubiquitin activating enzyme
Ubiquitin-activating enzyme
ubiquitin-activating enzyme E1
ubiquitin-conjugating enzyme
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine = AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine = AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
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ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine = AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
ATP-dependant formation of C-S thioester bond between the C-terminal glycine of ubiquitin and a sulfhydryl side group of a cysteine residue on the E1 protein
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine = AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
in the ATP-dependent activation reaction, ubiquitin is covalently attached to a cysteine residue of the E1 component through a thiol ester bond
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ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine = AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
E1 consumes ATP and converts ubiquitin to a transfer-competent, enzyme-bound thioester. The reaction begins with ubiquitin-adenylate formation and the release of diphosohate. The active site cysteine of the E1 then displaces the AMP leading to a ubiquitin-E1 thioester complex
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine = AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
modeling of a cis-binding mechanism of UFM1 to UBA5, trans-binding mechanism of UFM1 transfer to the E2, UFC1, and UFM1-UBA5 adenylation domain interactions, overview. Although the active site Cys in the UBA5 apo structure is located at the N terminus of helix H, this Cys is no longer part of a helical structure in the complex with UFM1. Conformational changes in UBA5 are required to bring the active site Cys into the vicinity of UFM1-AMP mixed anhydride bond, leading to formation of the thioester bond
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PATHWAY SOURCE
PATHWAYS
MetaCyc
protein ubiquitination
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SYSTEMATIC NAME
IUBMB Comments
ubiquitin:[E1 ubiquitin-activating enzyme] ligase (AMP-forming)
Catalyses the ATP-dependent activation of ubiquitin through the formation of a thioester bond between the C-terminal glycine of ubiquitin and the sulfhydryl side group of a cysteine residue in the E1 protein. The two-step reaction consists of the ATP-dependent formation of an E1-ubiquitin adenylate intermediate in which the C-terminal glycine of ubiquitin is bound to AMP via an acyl-phosphate linkage, then followed by the conversion to an E1-ubiquitin thioester bond via the cysteine residue on E1 in the second step.
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + Oregon Green-labeled ubiquitin + [ubiquitin-activating protein E1]-L-cysteine
AMP + diphosphate + [ubiquitin-activating protein E1]-S-(Oregon Green-labeled ubiquitinyl)-L-cysteine
-
Substrates: enzyme efficiently accepts ubiquitin substrate fluorescently labeled by Oregon Green
Products: -
Products: -
?
ATP + SUMO2 + [ubiquitin-activating protein UBA5]-L-cysteine
AMP + diphosphate + [ubiquitin-activating protein UBA5]-S-SUMO2-L-cysteine
Substrates: SUMO2, small ubiquitin-like modifier2, an ubiquitin-like protein
Products: enzyme greatly activates SUMO2 in the nucleus or transfers activated SUMO2 to the nucleus after it conjugated SUMO2 in the cytoplasm
Products: enzyme greatly activates SUMO2 in the nucleus or transfers activated SUMO2 to the nucleus after it conjugated SUMO2 in the cytoplasm
?
ATP + ubiquitin + SUMO2
?
Substrates: UBE1DC1 greatly activates SUMO2 in the nucleus or transfers activated-SUMO2 to nucleus after conjugation of SUMO2 in the cytoplasm
Products: -
Products: -
?
ATP + ubiquitin + ubiquitin carrier protein E2
AMP + diphosphate + ubiquitin-(ubiquitin carrier protein E2)
-
Substrates: -
Products: -
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?
ATP + ubiquitin + ubiquitin-fold modifier 1
?
Substrates: -
Products: -
Products: -
?
ATP + ubiquitin + [6His-ubiquitin-activating enzyme E1]W-8His-Strep-HA
AMP + diphosphate + [6His-ubiquitin-activating enzyme E1]W-8His-Strep-HA-ubiquitinyl-L-cysteine
Substrates: Strep, i.e.WSHPQFEK, HA, i.e. YPYDVPDYAS, under non-reducing conditions, the intermediate complex of the thioester formation is not observed without ATP
Products: -
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?
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
ATP + ubiquitin + [ubiquitin-activating enzyme Uba5]-L-cysteine
AMP + diphosphate + [ubiquitin-activating enzyme Uba5]-S-ubiquitinyl-L-cysteine
Substrates: the catalytic cysteine residue of isoform Uba5 is part of the adenylation domain in a alpha-helical motif
Products: -
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?
ATP + ubiquitin + [ubiquitin-activating protein E1]-L-cysteine
AMP + diphosphate + [ubiquitin-activating protein E1]-S-ubiquitinyl-L-cysteine
ATP + ubiquitin + [ubiquitin-activating protein Uba1a]-L-cysteine
AMP + diphosphate + [ubiquitin-activating protein Uba1a]-S-ubiquitinyl-L-cysteine
-
Substrates: -
Products: -
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?
ATP + ubiquitin + [ubiquitin-activating protein UBA1]-L-cysteine
AMP + diphosphate + [ubiquitin-activating protein UBA1]-S-ubiquitinyl-L-cysteine
Substrates: enzyme forms higher molecular mass intermediates with ubiquitin
Products: the enzyme-ubiquitin intermediates dissociate in presence of 2-mercaptoethanol, indicating thiolester linkage
Products: the enzyme-ubiquitin intermediates dissociate in presence of 2-mercaptoethanol, indicating thiolester linkage
?
ATP + ubiquitin + [ubiquitin-activating protein UBA2]-L-cysteine
AMP + diphosphate + [ubiquitin-activating protein UBA2]-S-ubiquitinyl-L-cysteine
Substrates: enzyme forms higher molecular mass intermediates with ubiquitin
Products: the enzyme-ubiquitin intermediates dissociate in presence of 2-mercaptoethanol, indicating thiolester linkage
Products: the enzyme-ubiquitin intermediates dissociate in presence of 2-mercaptoethanol, indicating thiolester linkage
?
ATP + ubiquitin + [ubiquitin-activating protein Uba6]-L-cysteine
AMP + diphosphate + [ubiquitin-activating protein Uba6]-S-ubiquitinyl-L-cysteine
Substrates: isoform Uba6 forms a covalent link with ubiquitin in vitro and in vivo, which is sensitive to reducing conditions. Recombinant E1 enzyme Uba6 can activate ubiquitin and transfer it onto the ubiquitin-conjugating enzyme UbcH5B. Ubiquitin activated by Uba6 can be used for ubiquitylation of p53 and supports the autoubiquitylation of the E3 ubiquitin ligases HectH9 and E6-AP
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?
ATP + ubiquitin + [ubiquitin-activating protein UBE1]-L-cysteine
AMP + diphosphate + [ubiquitin-activating protein UBE1]-S-ubiquitinyl-L-cysteine
Substrates: -
Products: -
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?
ATP + ubiquitin fold modifier1 + [ubiquitin-activating enzyme Uba5]-L-cysteine
AMP + diphosphate + [ubiquitin-activating enzyme Uba5]-S-(ubiquitin fold modifier1)-L-cysteine
Substrates: the catalytic cysteine residue of isoform Uba5 is part of the adenylation domain in a alpha-helical motif
Products: -
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?
ATP + ubiquitin mutant G76A + [ubiquitin-activating protein E1]-L-cysteine
AMP + diphosphate + [ubiquitin-activating protein E1]-S-(ubiquitin mutant G76A)yl-L-cysteine
-
Substrates: -
Products: mutant ubiquitin G76A, bearing a Gly to Ala substitution at the COOH terminus is a substrate for El enzyme. Ubiquitin G76A supports PPI-ATP exchange with 500fold decrease in kcat/Km compared to wild-type ubiquitin, does not produce detectable AMP-Ub with native El, produces stoichiometric AMP-Ub with thiol-blocked El, gives a stoichiometric burst of ATP consumption with either native or thiol-blocked El, support El-ubiquitin thiol ester formation with native El, and supports several downstream reactions of the proteolytic pathway with a 20% decrease to the rate of wild type ubiquitin
Products: mutant ubiquitin G76A, bearing a Gly to Ala substitution at the COOH terminus is a substrate for El enzyme. Ubiquitin G76A supports PPI-ATP exchange with 500fold decrease in kcat/Km compared to wild-type ubiquitin, does not produce detectable AMP-Ub with native El, produces stoichiometric AMP-Ub with thiol-blocked El, gives a stoichiometric burst of ATP consumption with either native or thiol-blocked El, support El-ubiquitin thiol ester formation with native El, and supports several downstream reactions of the proteolytic pathway with a 20% decrease to the rate of wild type ubiquitin
?
ATP + Ufm1 + [ubiquitin-activating protein UBA5]-L-cysteine
AMP + diphosphate + [ubiquitin-activating protein UBA5]-S-Ufm1-L-cysteine
Substrates: Ufm1, ubiquitin-fold modifier 1, an ubiquitin-like protein
Products: -
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?
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
Substrates: -
Products: -
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?
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
-
Substrates: -
Products: -
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?
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
-
Substrates: -
Products: -
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?
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
Substrates: -
Products: -
Products: -
?
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
Giardia duodenalis ATCC 50803
Substrates: -
Products: -
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?
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
-
Substrates: E1-activating enzyme activates ubiquitin via an adenylated intermediate and catalyzes its transfer to an E2 enzyme
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?
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
-
Substrates: -
Products: -
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?
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
Substrates: -
Products: -
Products: -
?
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
-
Substrates: E1 activates ubiquitin or an ubiquitin-like protein and transfers it to the E2-conjugating enzyme
Products: -
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?
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
Substrates: -
Products: -
Products: -
?
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
Substrates: -
Products: -
Products: -
?
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
Substrates: -
Products: -
Products: -
?
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
Substrates: -
Products: -
Products: -
?
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
Substrates: -
Products: -
Products: -
?
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
Substrates: -
Products: -
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?
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
-
Substrates: -
Products: -
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?
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
A0A6P7D3I5
Substrates: -
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ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
Substrates: -
Products: -
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?
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
Substrates: -
Products: -
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?
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
-
Substrates: -
Products: -
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?
ATP + ubiquitin + [ubiquitin-activating protein E1]-L-cysteine
AMP + diphosphate + [ubiquitin-activating protein E1]-S-ubiquitinyl-L-cysteine
-
Substrates: -
Products: -
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?
ATP + ubiquitin + [ubiquitin-activating protein E1]-L-cysteine
AMP + diphosphate + [ubiquitin-activating protein E1]-S-ubiquitinyl-L-cysteine
-
Substrates: a carboxylgroup is first activated as an adenylate followed by its direct transfer to an autonomous molecular moiety in a single enzymatic step
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ATP + ubiquitin + [ubiquitin-activating protein E1]-L-cysteine
AMP + diphosphate + [ubiquitin-activating protein E1]-S-ubiquitinyl-L-cysteine
-
Substrates: -
Products: -
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?
ATP + ubiquitin + [ubiquitin-activating protein E1]-L-cysteine
AMP + diphosphate + [ubiquitin-activating protein E1]-S-ubiquitinyl-L-cysteine
-
Substrates: -
Products: -
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?
additional information
?
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Substrates: a lysine 48-linked polyubiquitin chain, assembled upon an internal lysine residue of a substrate protein, becomes the principle signal for recognition and target degradation by the 26S proteasome. E1 is not only essential for the initial ATP-dependent activation of ubiquitin in the ubiquitin degradtion pathway, but also capable of the catalytic extension of the polyubiquitin chain on a mono-ubiquitinated substrate
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?
additional information
?
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-
Substrates: UBE1L2 transfers activated ubiquitin onto UbcH5b and supports E3-mediated polyubiquitylation
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?
additional information
?
-
Substrates: UBE1L2 transfers activated ubiquitin onto UbcH5b and supports E3-mediated polyubiquitylation
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additional information
?
-
-
Substrates: impaired nucleotide excision repair upon macrophage differentiation is corrected by E1 ubiquitin-activating enzyme
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additional information
?
-
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Substrates: the thioester formation assay is performed using recombinant proteins expressed in Escherichia coli. The activation of ubiquitin by purified UBE1 is identified in vitro by SDS-PAGE
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additional information
?
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Substrates: the thioester formation assay is performed using recombinant proteins expressed in Escherichia coli. The activation of ubiquitin by purified UBE1 is identified in vitro by SDS-PAGE
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additional information
?
-
Substrates: residue Cys194 lies within a region of identity to active-site Cys88 of the ubiquitin carrier protein E2, suggesting a potential role for this region in enzymatic function. Residue Cys454 lies within a region of identity to the thiol ester consensus sequence of several proteins involved in thioester formation
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additional information
?
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Substrates: residue Cys194 lies within a region of identity to active-site Cys88 of the ubiquitin carrier protein E2, suggesting a potential role for this region in enzymatic function. Residue Cys454 lies within a region of identity to the thiol ester consensus sequence of several proteins involved in thioester formation
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additional information
?
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Substrates: kinetics for Uba1a-catalyzed transthiolation of Ubc2b are used as a reporter assay for determining the Km and kcat values for the three cosubstrates of the ubiquitin-activating enzyme. The E2 transthiolation assays are more sensitive to the potential presence of trace catalytically active fragments than the single turnover end point assays used for quantitating ternary complex stoichiometry
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additional information
?
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Substrates: purified isoform UBE1 can activate and conjugate ubiquitin to ubiquitin-conjugating enzyme E2s. Transfer is restricted to distinct E2 isoforms UB2R2, UBE2W and UBE2NL
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additional information
?
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Substrates: purified isoform UBE1 can activate and conjugate ubiquitin to ubiquitin-conjugating enzyme E2s. Transfer is restricted to distinct E2 isoforms UB2R2, UBE2W and UBE2NL
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additional information
?
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Substrates: E1 ubiquitin-activating enzyme UBA6 is the only E1 enzyme that can activate both ubiquitin and ubiquitin-like protein HLA-F adjacent transcript 10 (FAT10). FAT10 consists of two ubiquitin-like domains with 29% and 36% identity to ubiquitin, respectively, that are separated by a short linker region
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additional information
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Substrates: orthogonal ubiquitin transfer (OUT) technology to profile their ubiquitination targets in mammalian cells of isozymes Uba1 and Uba6
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additional information
?
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Substrates: orthogonal ubiquitin transfer (OUT) technology to profile their ubiquitination targets in mammalian cells of isozymes Uba1 and Uba6
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additional information
?
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Substrates: the non-canonical E1, UBA5, binds to the ubiquitin-like protein UFM1 using a trans-binding mechanism in which UFM1 interacts with distinct sites in both subunits of the UBA5 dimer. Mechanism of UFM1 activation by UBA5 and trans-binding mechanism of UFM1 transfer to the E2, UFC1. UFM1 contains a C-terminal Val-Gly dipeptide instead of the canonical Gly-Gly dipeptide present in ubiquitin and other ubiquitin-like proteins
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additional information
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Substrates: CDC42 is a substrate of UBA6-initiated ubiquitination
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additional information
?
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Substrates: CDC42 is a substrate of UBA6-initiated ubiquitination
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additional information
?
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Substrates: E1 consumes ATP and converts ubiquitin to a transfer-competent, enzyme-bound thioester. The reaction begins with ubiquitin-adenylate formation and the release of diphosohate. The active site cysteine of the E1 then displaces the AMP leading to a ubiquitin-E1 thioester complex
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Products: -
?
additional information
?
-
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Substrates: E1 consumes ATP and converts ubiquitin to a transfer-competent, enzyme-bound thioester. The reaction begins with ubiquitin-adenylate formation and the release of diphosohate. The active site cysteine of the E1 then displaces the AMP leading to a ubiquitin-E1 thioester complex
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additional information
?
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Substrates: E1 activity is assesssed by the capacity of the enzyme to form a thiol ester conjugate with ubiquitin in an ATP-dependent process and to transfer this activated ubiquitin molecule to an conjugating enzyme
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additional information
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Substrates: chimeric mutant Aos1-Uba2 SUMO-E1 enzyme shows SUMO-E1 activity. The E1 enzyme catalyzes the formation of a thioester-linked complex between SUMO and the E2 enzyme. This process is initiated by activation of the carboxyl terminus of SUMO by adenylation, followed by a thioesterification reaction in which SUMO is conjugated to a cysteine residue at the active site of Uba2 in the E1 enzyme. SUMO is then transferred to the active site cysteine of the E2 enzyme, Ubc9, via a trans-thioesterification reaction. A SUMO-charged E2 enzyme and substrate are finally bound with or without the assistance of a distinct class of SUMO E3-ligases, resulting in the activated SUMO bound to the substrate through an isopeptide linkage
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
Substrates: -
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ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
-
Substrates: -
Products: -
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ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
-
Substrates: -
Products: -
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?
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
Substrates: -
Products: -
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?
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
Giardia duodenalis ATCC 50803
Substrates: -
Products: -
Products: -
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ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
-
Substrates: E1-activating enzyme activates ubiquitin via an adenylated intermediate and catalyzes its transfer to an E2 enzyme
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ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
-
Substrates: -
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ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
Substrates: -
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ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
Substrates: -
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ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
Substrates: -
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ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
Substrates: -
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ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
Substrates: -
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ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
Substrates: -
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ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
Substrates: -
Products: -
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ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
-
Substrates: -
Products: -
Products: -
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ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
A0A6P7D3I5
Substrates: -
Products: -
Products: -
?
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
Substrates: -
Products: -
Products: -
?
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
Substrates: -
Products: -
Products: -
?
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
-
Substrates: -
Products: -
Products: -
?
additional information
?
-
-
Substrates: a lysine 48-linked polyubiquitin chain, assembled upon an internal lysine residue of a substrate protein, becomes the principle signal for recognition and target degradation by the 26S proteasome. E1 is not only essential for the initial ATP-dependent activation of ubiquitin in the ubiquitin degradtion pathway, but also capable of the catalytic extension of the polyubiquitin chain on a mono-ubiquitinated substrate
Products: -
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additional information
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-
-
Substrates: UBE1L2 transfers activated ubiquitin onto UbcH5b and supports E3-mediated polyubiquitylation
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additional information
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-
Substrates: UBE1L2 transfers activated ubiquitin onto UbcH5b and supports E3-mediated polyubiquitylation
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additional information
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-
-
Substrates: impaired nucleotide excision repair upon macrophage differentiation is corrected by E1 ubiquitin-activating enzyme
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additional information
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-
Substrates: E1 ubiquitin-activating enzyme UBA6 is the only E1 enzyme that can activate both ubiquitin and ubiquitin-like protein HLA-F adjacent transcript 10 (FAT10). FAT10 consists of two ubiquitin-like domains with 29% and 36% identity to ubiquitin, respectively, that are separated by a short linker region
Products: -
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additional information
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Substrates: orthogonal ubiquitin transfer (OUT) technology to profile their ubiquitination targets in mammalian cells of isozymes Uba1 and Uba6
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additional information
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Substrates: orthogonal ubiquitin transfer (OUT) technology to profile their ubiquitination targets in mammalian cells of isozymes Uba1 and Uba6
Products: -
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additional information
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Substrates: E1 consumes ATP and converts ubiquitin to a transfer-competent, enzyme-bound thioester. The reaction begins with ubiquitin-adenylate formation and the release of diphosohate. The active site cysteine of the E1 then displaces the AMP leading to a ubiquitin-E1 thioester complex
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additional information
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Substrates: E1 consumes ATP and converts ubiquitin to a transfer-competent, enzyme-bound thioester. The reaction begins with ubiquitin-adenylate formation and the release of diphosohate. The active site cysteine of the E1 then displaces the AMP leading to a ubiquitin-E1 thioester complex
Products: -
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Zinc
isoform UBA5 maintains a zinc-binding site that is coordinated by four cysteines with tetrahedral geometry
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(3E)-4-[(5R,8S)-5-methyl-6,9,13-trioxo-8-(propan-2-yl)-10-oxa-3,17-dithia-7,14,19,20-tetraazatricyclo[14.2.1.1~2,5~]icosa-1(18),2(20),16(19)-trien-11-yl]but-3-en-1-yl octanoate
(5R,8S)-11-ethenyl-5-methyl-8-(propan-2-yl)-10-oxa-3,17-dithia-7,14,19,20-tetraazatricyclo[14.2.1.1~2,5~]icosa-1(18),2(20),16(19)-triene-6,9,13-trione
(5R,8S)-5-methyl-11-[(1E)-6-oxotridec-1-en-1-yl]-8-(propan-2-yl)-10-oxa-3,17-dithia-7,14,19,20-tetraazatricyclo[14.2.1.1~2,5~]icosa-1(18),2(20),16(19)-triene-6,9,13-trione
(5R,8S)-5-methyl-8-(propan-2-yl)-11-[(1E)-4-sulfanylbut-1-en-1-yl]-10-oxa-3,17-dithia-7,14,19,20-tetraazatricyclo[14.2.1.1~2,5~]icosa-1(18),2(20),16(19)-triene-6,9,13-trione
5'-[[(L-cysteinylglycylglycyl)sulfamoyl]amino]-5'-deoxyadenosine
-
inhibits Uba1-S-Ub thioester formation in a dose-dependent manner. The inhibitor is highly selective for its cognate E1 enzyme and does not inhibit the corresponding non-cognate E1s
AtMUB3
the MUB3 protein of Arabidopsis thaliana strongly reduces the E2-ubiquitin formation by E1. Inhibitory effects of wild-type and mutant MUB3 proteins, overview; the MUB3 protein of Arabidopsis thaliana strongly reduces the E2-ubiquitin formation by E1. Inhibitory effects of wild-type and mutant MUB3 proteins, overview
-
ginsenoside Re
-
inhibits ubiquitin-activating enzyme, from Panax ginseng roots, a traditional herbal medicine or food
ginsenoside Rg1
-
inhibit ubiquitin-activating enzyme, from Panax ginseng roots, a traditional herbal medicine or food, causes 89.2% inhibition at 0.05 mM
largazole
-
largazole and its ester and ketone analogues selectively inhibit human UBA1 enzyme and inhibit ubiquitin conjugation to cyclin-dependent kinase inhibitor p27Kip1 and TRF1 in vitro, mechanism of E1 inhibition, overview. Largazole and its derivatives specifically inhibit the adenylation step of the E1 reaction while having no effect on thioester bond formation between ubiquitin and E1. Upon incubation with E1, largazole or largazole ester reduce the amount of ubiquitin molecules that are transferred from E1 to E2 in a dose-dependent fashion. E1 inhibition appears to be specific to human E1. Largazole analogues do not significantly inhibit SUMO E1
LMO2
interaction between LMO2 and UBA6 blocks the recruitment of USE1 by UBA6 in a dose-dependent manner.. The LMO2 protein interacts with the E1 ubiquitin-activating enzyme UBA6 at the C-terminal ubiquitin fold domain (UFD), which mediates the recognition and recruitment of the E2-conjugating enzyme USE1. The LMO2-UBA6 interaction leads to the decline of the overall cellular FAT10ylation level as well as the FAT10ylation and degradation of a known FAT10 substrate p62. Interaction analysis of LMO2 with isolated UBA6 domains, LMO2 interacts with UBA6 at the ubiquitin-fold domain, overview. LMO2 co-localizes with UBA6 and USE1 primarily in the cytoplasm of epithelium-derived cells
-
S-[(3E)-5-hydroxy-7-({[(4R)-4-{[(3S)-2-methoxy-4-methylpent-1-en-3-yl]carbamoyl}-4-methyl[4,5-dihydro[2,4'-bi-1,3-thiazole]]-2'-yl]methyl}amino)-7-oxohept-3-en-1-yl] octanethioate
(3E)-4-[(5R,8S)-5-methyl-6,9,13-trioxo-8-(propan-2-yl)-10-oxa-3,17-dithia-7,14,19,20-tetraazatricyclo[14.2.1.1~2,5~]icosa-1(18),2(20),16(19)-trien-11-yl]but-3-en-1-yl octanoate
-
-
(3E)-4-[(5R,8S)-5-methyl-6,9,13-trioxo-8-(propan-2-yl)-10-oxa-3,17-dithia-7,14,19,20-tetraazatricyclo[14.2.1.1~2,5~]icosa-1(18),2(20),16(19)-trien-11-yl]but-3-en-1-yl octanoate
-
-
(5R,8S)-11-ethenyl-5-methyl-8-(propan-2-yl)-10-oxa-3,17-dithia-7,14,19,20-tetraazatricyclo[14.2.1.1~2,5~]icosa-1(18),2(20),16(19)-triene-6,9,13-trione
-
-
(5R,8S)-11-ethenyl-5-methyl-8-(propan-2-yl)-10-oxa-3,17-dithia-7,14,19,20-tetraazatricyclo[14.2.1.1~2,5~]icosa-1(18),2(20),16(19)-triene-6,9,13-trione
-
-
(5R,8S)-5-methyl-11-[(1E)-6-oxotridec-1-en-1-yl]-8-(propan-2-yl)-10-oxa-3,17-dithia-7,14,19,20-tetraazatricyclo[14.2.1.1~2,5~]icosa-1(18),2(20),16(19)-triene-6,9,13-trione
-
-
(5R,8S)-5-methyl-11-[(1E)-6-oxotridec-1-en-1-yl]-8-(propan-2-yl)-10-oxa-3,17-dithia-7,14,19,20-tetraazatricyclo[14.2.1.1~2,5~]icosa-1(18),2(20),16(19)-triene-6,9,13-trione
-
-
(5R,8S)-5-methyl-8-(propan-2-yl)-11-[(1E)-4-sulfanylbut-1-en-1-yl]-10-oxa-3,17-dithia-7,14,19,20-tetraazatricyclo[14.2.1.1~2,5~]icosa-1(18),2(20),16(19)-triene-6,9,13-trione
-
-
(5R,8S)-5-methyl-8-(propan-2-yl)-11-[(1E)-4-sulfanylbut-1-en-1-yl]-10-oxa-3,17-dithia-7,14,19,20-tetraazatricyclo[14.2.1.1~2,5~]icosa-1(18),2(20),16(19)-triene-6,9,13-trione
-
-
1-(3-chloro-4-fluorophenyl)-4-[(5-nitro-2-furyl)methylene]-3,5-pyrazolidinedione
-
i.e. PYZD-4409, small molecule inhibitor. PYZD-4409 induces cell death in malignant cells and preferentially inhibits the clonogenic growth of primary acute myeloid leukemia cells compared with normal hematopoietic cells
1-(3-chloro-4-fluorophenyl)-4-[(5-nitro-2-furyl)methylene]-3,5-pyrazolidinedione
-
i.e. PYZD-4409. In a mouse model of leukemia, intraperitoneal administration of PYZD-4409 decreases tumor weight and volume compared with control without untoward toxicity
4[4-(5-nitro-furan-2-ylmethylene)-3,5-dioxo-pyrazolidin-1-yl]-benzoic acid ethyl ester
-
i.e. Pyr-41. Inhibitor blocks loading of immobilized His6-tagged E1 with ubiquitin. PYR-41 does not affect the transfer of ubiquitin to E2 from E1 that is preloaded with ubiquitin, it directly inhibits E1, but not E2 enzymes. In addition to blocking ubiquitylation, PYR-41 increases total sumoylation in cells. PYR-41 attenuates cytokine-mediated nuclear factor-kappaB activation. This correlates with inhibition of nonproteasomal Lys63 ubiquitylation of TRAF6, which is essential to IkappaB kinase activation
4[4-(5-nitro-furan-2-ylmethylene)-3,5-dioxo-pyrazolidin-1-yl]-benzoic acid ethyl ester
i.e. PYR-41
4[4-(5-nitro-furan-2-ylmethylene)-3,5-dioxo-pyrazolidin-1-yl]-benzoic acid ethyl ester
-
i.e. PYR-41, potential of the inhibitor as therapeutic in cancer
S-[(3E)-5-hydroxy-7-({[(4R)-4-{[(3S)-2-methoxy-4-methylpent-1-en-3-yl]carbamoyl}-4-methyl[4,5-dihydro[2,4'-bi-1,3-thiazole]]-2'-yl]methyl}amino)-7-oxohept-3-en-1-yl] octanethioate
-
-
S-[(3E)-5-hydroxy-7-({[(4R)-4-{[(3S)-2-methoxy-4-methylpent-1-en-3-yl]carbamoyl}-4-methyl[4,5-dihydro[2,4'-bi-1,3-thiazole]]-2'-yl]methyl}amino)-7-oxohept-3-en-1-yl] octanethioate
-
-
additional information
Arabidopsis thaliana MUBs1-6 interact specifically with the Arabidopsis thaliana group VI E2 family proteins, MUBs specifically inhibit activation of these critical Ub E2s; Arabidopsis thaliana MUBs1-6 interact specifically with the Arabidopsis thaliana group VI E2 family proteins, MUBs specifically inhibit activation of these critical Ub E2s
-
additional information
Arabidopsis thaliana MUBs1-6 interact specifically with the Arabidopsis thaliana group VI E2 family proteins, MUBs specifically inhibit activation of these critical Ub E2s; Arabidopsis thaliana MUBs1-6 interact specifically with the Arabidopsis thaliana group VI E2 family proteins, MUBs specifically inhibit activation of these critical Ub E2s
-
additional information
individual E1 enzyme domains like SCCH show the potential to interfere with cellular processes by acting as competitive inhibitors in protein-protein interactions involving complete proteins
-
additional information
-
individual E1 enzyme domains like SCCH show the potential to interfere with cellular processes by acting as competitive inhibitors in protein-protein interactions involving complete proteins
-
additional information
-
largazole and its ester and ketone analogues selectively inhibit ubiquitin conjugation to p27Kip1 and TRF1 in vitro, but the inhibition appears to be specific to human E1. Largazole analogues do not significantly inhibit Uba1p
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ginsenoside Rb1
-
increases ubiquitination on E1 enzyme, from Panax ginseng roots, a traditional herbal medicine or food
ginsenoside Rb2
-
increases ubiquitination on E1 enzyme, from Panax ginseng roots, a traditional herbal medicine or food
ginsenoside Rc
-
increases ubiquitination on E1 enzyme, from Panax ginseng roots, a traditional herbal medicine or food
ginsenoside Rd
-
increases ubiquitination on E1 enzyme, from Panax ginseng roots, a traditional herbal medicine or food
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0011
ubiquitin
-
mutant D576E, pH 7.5, temperature not specified in the publication
0.0023
ubiquitin
-
mutant K528A, pH 7.5, temperature not specified in the publication
0.004
ubiquitin
-
mutant D576N, pH 7.5, temperature not specified in the publication
0.008
ubiquitin
-
wild-type, pH 7.5, temperature not specified in the publication
0.029
ubiquitin
-
mutant D576A, pH 7.5, temperature not specified in the publication
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.005
ATP
-
above, intrinsic kcat for ubiquitin adenylate formation corrected for saturating ATP and 125I-ubiquitin, mutant enzyme D576E
0.011
ATP
-
above, intrinsic kcat for ubiquitin adenylate formation corrected for saturating ATP and 125I-ubiquitin, mutant enzyme D576N
0.011
ATP
-
intrinsic kcat for transthiolation of ubiquitin carrier protein E2 corrected for saturating ATP, 125I-ubiquitin, and ubiquitin carrier protein E2, mutant enzyme K528A
0.015
ATP
-
above, intrinsic kcat for ubiquitin adenylate formation corrected for saturating ATP and 125I-ubiquitin, mutant enzyme K528A
0.022
ATP
-
intrinsic kcat for transthiolation of ubiquitin carrier protein E2 corrected for saturating ATP, 125I-ubiquitin, and ubiquitin carrier protein E2, mutant enzyme D576N
0.024
ATP
-
above, intrinsic kcat for ubiquitin adenylate formation corrected for saturating ATP and 125I-ubiquitin, mutant enzyme D576A
0.1
ATP
-
intrinsic kcat for transthiolation of ubiquitin carrier protein E2 corrected for saturating ATP, 125I-ubiquitin, and ubiquitin carrier protein E2, mutant enzyme D576E
0.12
ATP
-
intrinsic kcat for transthiolation of ubiquitin carrier protein E2 corrected for saturating ATP, 125I-ubiquitin, and ubiquitin carrier protein E2, mutant enzyme D576A
3.4
ATP
-
intrinsic kcat for transthiolation of ubiquitin carrier protein E2 corrected for saturating ATP, 125I-ubiquitin, and ubiquitin carrier protein E2, wild-type enzyme
6
ATP
-
above, intrinsic kcat for ubiquitin adenylate formation corrected for saturating ATP and 125I-ubiquitin, wild-type enzyme
0.005
ubiquitin
-
above, intrinsic kcat for ubiquitin adenylate formation corrected for saturating ATP and 125I-ubiquitin, mutant enzyme D576E
0.011
ubiquitin
-
above, intrinsic kcat for ubiquitin adenylate formation corrected for saturating ATP and 125I-ubiquitin, mutant enzyme D576N
0.011
ubiquitin
-
intrinsic kcat for transthiolation of ubiquitin carrier protein E2 corrected for saturating ATP, 125I-ubiquitin, and ubiquitin carrier protein E2, mutant enzyme K528A
0.015
ubiquitin
-
above, intrinsic kcat for ubiquitin adenylate formation corrected for saturating ATP and 125I-ubiquitin, mutant enzyme K528A
0.022
ubiquitin
-
intrinsic kcat for transthiolation of ubiquitin carrier protein E2 corrected for saturating ATP, 125I-ubiquitin, and ubiquitin carrier protein E2, mutant enzyme D576N
0.024
ubiquitin
-
above, intrinsic kcat for ubiquitin adenylate formation corrected for saturating ATP and 125I-ubiquitin, mutant enzyme D576A
0.1
ubiquitin
-
intrinsic kcat for transthiolation of ubiquitin carrier protein E2 corrected for saturating ATP, 125I-ubiquitin, and ubiquitin carrier protein E2, mutant enzyme D576E
0.12
ubiquitin
-
intrinsic kcat for transthiolation of ubiquitin carrier protein E2 corrected for saturating ATP, 125I-ubiquitin, and ubiquitin carrier protein E2, mutant enzyme D576A
3.4
ubiquitin
-
intrinsic kcat for transthiolation of ubiquitin carrier protein E2 corrected for saturating ATP, 125I-ubiquitin, and ubiquitin carrier protein E2, wild-type enzyme
6
ubiquitin
-
above, intrinsic kcat for ubiquitin adenylate formation corrected for saturating ATP and 125I-ubiquitin, wild-type enzyme
0.005
ubiquitin carrier protein E2
-
above, intrinsic kcat for ubiquitin adenylate formation corrected for saturating ATP and 125I-ubiquitin, mutant enzyme D576E
0.011
ubiquitin carrier protein E2
-
above, intrinsic kcat for ubiquitin adenylate formation corrected for saturating ATP and 125I-ubiquitin, mutant enzyme D576N
0.011
ubiquitin carrier protein E2
-
intrinsic kcat for transthiolation of ubiquitin carrier protein E2 corrected for saturating ATP, 125I-ubiquitin, and ubiquitin carrier protein E2, mutant enzyme K528A
0.015
ubiquitin carrier protein E2
-
above, intrinsic kcat for ubiquitin adenylate formation corrected for saturating ATP and 125I-ubiquitin, mutant enzyme K528A
0.022
ubiquitin carrier protein E2
-
intrinsic kcat for transthiolation of ubiquitin carrier protein E2 corrected for saturating ATP, 125I-ubiquitin, and ubiquitin carrier protein E2, mutant enzyme D576N
0.024
ubiquitin carrier protein E2
-
above, intrinsic kcat for ubiquitin adenylate formation corrected for saturating ATP and 125I-ubiquitin, mutant enzyme D576A
0.1
ubiquitin carrier protein E2
-
intrinsic kcat for transthiolation of ubiquitin carrier protein E2 corrected for saturating ATP, 125I-ubiquitin, and ubiquitin carrier protein E2, mutant enzyme D576E
0.12
ubiquitin carrier protein E2
-
intrinsic kcat for transthiolation of ubiquitin carrier protein E2 corrected for saturating ATP, 125I-ubiquitin, and ubiquitin carrier protein E2, mutant enzyme D576A
3.4
ubiquitin carrier protein E2
-
intrinsic kcat for transthiolation of ubiquitin carrier protein E2 corrected for saturating ATP, 125I-ubiquitin, and ubiquitin carrier protein E2, wild-type enzyme
6
ubiquitin carrier protein E2
-
above, intrinsic kcat for ubiquitin adenylate formation corrected for saturating ATP and 125I-ubiquitin, wild-type enzyme
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
4[4-(5-nitro-furan-2-ylmethylene)-3,5-dioxo-pyrazolidin-1-yl]-benzoic acid ethyl ester
Homo sapiens
-
inhibitor blocks loading of immobilized His6-tagged E1 with ubiquitin with an IC50 below 10 microM
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
37
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
cv. Wuzishatangju (seedless) and cv. Shatangju (seedy), single copy gene CrUBE1
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
mouse embryo fibroblast cell, thermosensitive for ubiquitin-activating enzyme E1
brenda
-
expression level of the CrUBE1 gene in anthers of cv. Shatangju is approximately 10fold higher than in anthers of cv. Wuzishatangju
brenda
A0A6P7D3I5
ovine thymuses are sampled on day 16 of the estrous cycle and on days 13, 16 and 25 of gestation, and UBE1L is detected by real-time quantitative PCR, Western blot and immunohistochemistry. The expression of UBE1L is declined during early pregnancy
brenda
additional information
the enzyme localizes at spots within the cytoplasm. This pattern changes during encystation into a diffuse localization throughout the cytoplasm of encysting cells. E1 localizes in mature cysts at cytoplasmic spots and in the cyst wall
brenda
Giardia duodenalis ATCC 50803
-
the enzyme localizes at spots within the cytoplasm. This pattern changes during encystation into a diffuse localization throughout the cytoplasm of encysting cells. E1 localizes in mature cysts at cytoplasmic spots and in the cyst wall
-
brenda
E1 localizes in the trophozoites in a precise pattern bound to small granules or vesicles
brenda
Giardia duodenalis ATCC 50803
-
E1 localizes in the trophozoites in a precise pattern bound to small granules or vesicles
-
brenda
additional information
-
semi-quantitative and quantitative expressio analysis of the enzyme in different tissues of the two cultivars, o verview, the highest expression level of CrUBE1 is detected in pistils at 7 days after self pollination of cv.Wuzishatangju, which is approximately 5fold higher than at the starting point
brenda
additional information
the enzyme expression (both at mRNA and protein levels) is regulated during encystation
brenda
additional information
Giardia duodenalis ATCC 50803
-
the enzyme expression (both at mRNA and protein levels) is regulated during encystation
-
brenda
additional information
-
primary leukemia and multiple myolema patient samples
brenda
additional information
isoform UBA1 mRNA is detected in all tissues analyzed
brenda
additional information
-
isoform UBA1 mRNA is detected in all tissues analyzed
brenda
additional information
the enzyme (UBA1) exhibits ubiquitous expression throughout all human tissues
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
the enzyme localizes at spots within the cytoplasm, this pattern changes during encystation into a diffuse localization throughout the cytoplasm of encysting cells. E1 localizes in mature cysts at cytoplasmic spots and in the cyst wall
brenda
Giardia duodenalis ATCC 50803
-
the enzyme localizes at spots within the cytoplasm, this pattern changes during encystation into a diffuse localization throughout the cytoplasm of encysting cells. E1 localizes in mature cysts at cytoplasmic spots and in the cyst wall
-
brenda
UBE1DC1 is especially distributed in the cytoplasm of AD-293 cells
brenda
UBE1DC1 is mainly distributed in the nucleus of AD-293 cells when cotransfected with its substrate SUMO2
brenda
predominant localization upon cotransfection with small ubiquitin-like modifier SUMO2
brenda
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
evolution
-
5 amino acids and 8 bases are different in cDNA and DNA sequences of CrUBE1 between Wuzishatangju and Shatangju, respectively
evolution
MUB inhibition of E1 is conserved between plants and humans
evolution
yeast Ub-activating enzyme E1 is a modular protein, evolved from small prokaryotic proteins, which had specific functions, and in E1 enzyme they form domains that work together as part of a big enzyme
evolution
-
yeast Ub-activating enzyme E1 is a modular protein, evolved from small prokaryotic proteins, which had specific functions, and in E1 enzyme they form domains that work together as part of a big enzyme
-
malfunction
-
identification of loss-of-function mutations in the Drosophila ubiquitin activating enzyme, the most upstream enzyme in the ubiquitin pathway. Loss of only one functional copy of E1 caused a significant reduction in adult lifespan. Rare homozygous hypomorphic E1 mutants reach adulthood, but mutants exhibit further reduced lifespan and show inappropriate Ras activation in the brain. Removing just one functional copy of Ras restores the lifespan of heterozygous E1 mutants to that of wild-type flies and increase the survival of homozygous E1 mutants. E1 homozygous mutants also show severe motor impairment involved in early mortality. Phenotypes, detailed overview
malfunction
the LMO2 protein interacts with the E1 ubiquitin-activating enzyme UBA6 at the C-terminal ubiquitin fold domain (UFD), which mediates the recognition and recruitment of the E2-conjugating enzyme USE1. Functionally, the LMO2-UBA6 interaction disturbes the interaction between UBA6 and USE1 and leads to the decline of the overall cellular FAT10ylation level as well as the FAT10ylation and degradation of a known FAT10 substrate p62
malfunction
local delivery of potent chemical UBA1 inhibitor PYR-41 and UBA1 shRNA lentivirus both result in a substantial decrease in intimal hyperplasia at 2 weeks and 4 weeks after balloon injury. UBA1 inhibition also reduces Ki-67 positive cell percentage and inflammatory response in the carotid artery wall. In vitro UBA1 inhibition is able to ameliorate TNF-alpha-induced nuclear factor-kappa B (NF-kappaB) activation by reducing IkappaB degradation in vascular smooth muscle cells (VSMCs). UBA1 inhibition also leads to the accumulation of short-lived proteins such as p53, p21 and c-jun, which may account for the UBA1 inhibition-induced cell cycle delay. Thus, VSMCs proliferation is blocked. UBA1 inhibition effectively suppresses neointimal thickening through its anti-proliferative and anti-inflammatory effects
malfunction
mammary epithelial MCF-10A cells expressing shRNA against UBA6 fail in establishing cell cycle arrest in response to detachment from extracellular matrix, confluency with fully engaged cell-cell contact or growth factor deprivation. Moreover, UBA6-deficient MCF-10A cells undergo spontaneous epithelial-mesenchymal transition (EMT) under growth factor deprivation and exhibit accelerated kinetics of TGF-beta-induced EMT. UBA6 knockdown perturbs acinar morphogenesis and leads to formation of gigantic cell aggregates in mammary epithelial 3-D culture. UBA6 depletion suppresses contact innhibition of the cell cycle. UBA6 downregulation promotes cancer progression such as EMT and invasion in a population of human breast cancers
malfunction
a defect in the UBA1 gene results in detrimental effects on cell cycle progression, and deletion of the UBA1 gene is lethal to the organism
malfunction
impaired UBA1 activity in a range of neurodegenerative conditions, including Parkinson's disease, Alzheimer's disease, Huntington's disease and spinal muscular atrophy
malfunction
-
a defect in the UBA1 gene results in detrimental effects on cell cycle progression, and deletion of the UBA1 gene is lethal to the organism
-
metabolism
-
the ubiquitin E1 activating enzyme ubiquitin-activating enzyme 1 (UBE1) is a putative substrate of FAT10. The ubiquitin-like modifier HLA-F adjacent transcript 10 (FAT10) directly targets its substrates for proteasomal degradation by becoming covalently attached via its C-terminal diglycine motif to internal lysine residues of its substrate proteins. UBE1 and FAT10 formed a stable isopeptide linkage. The conjugation machinery consists of the bispecific E1 activating enzyme ubiquitin-like modifier activating enzyme 6 (UBA6), the likewise bispecific E2 conjugating enzyme UBA6-specific E2 enzyme 1 (USE1), and possibly E3 ligases, overview. UBE1 and FAT10 form a stable non-reducible conjugate, FAT10ylation of UBE1 depends on the diglycine motif of FAT10
metabolism
-
ubiquitin-activating enzyme E1 catalyzes the first step in the ubiquitination reaction, which targets a protein for degradation via a proteasome pathway. The enzyme plays an important role in metabolic processes
metabolism
the ubiquitin-activating enzyme E1 (UBA1, E1) is the apex of the ubiquitin proteasome pathway
metabolism
A0A6P7D3I5
early pregnancy influences expression of STAT1, Mx1, IP-10 and UBE1L in maternal thymus, which may participate in regulation of maternal immune tolerance during early pregnancy in sheep
metabolism
ubiquitin-activating enzyme (E1) is the first enzyme of the ubiquitination pathway and is required to activate ubiquitin
metabolism
ubiquitin-activating enzyme E1, UBA1, functions at the apex of the enzymatic ubiquitylation cascade, catalysing ubiquitin activation. UBA1 is thus of fundamental importance to the modulation of ubiquitin homeostasis and to all downstream ubiquitylation-dependent cellular processes, including proteolysis through the ubiquitin-proteasome system and selective autophagy
metabolism
-
ubiquitin-activating enzyme (E1) is the first enzyme of the ubiquitination pathway and is required to activate ubiquitin
-
physiological function
-
knockdown of E1 decreases the abundance of ubiquitinated proteins in leukemia and myeloma cells and induces cell death. Inhibitor 1-(3-chloro-4-fluorophenyl)-4-[(5-nitro-2-furyl)methylene]-3,5-pyrazolidinedione, i.e. PYZD-4409, induces cell death in malignant cells and preferentially inhibits the clonogenic growth of primary acute myeloid leukemia cells compared with normal hematopoietic cells. Mechanistically, genetic or chemical inhibition of E1 increases expression of E1 stress markers. ER membrane protein BI-1 overexpression blocks cell death after E1 inhibition
physiological function
plays an important role in the first step of the proteasome pathway to activate ubiquitin. The UBE1 is a two-step intramolecular and ATP-dependent reaction to generate a high-energy E1-thiol-ester-ubiquitin intermediate. The activated ubiquitin are then transferred to ubiquitin-conjugating enzyme E2
physiological function
-
a lysine 48-linked polyubiquitin chain, assembled upon an internal lysine residue of a substrate protein, becomes the principle signal for recognition and target degradation by the 26S proteasome. E1 is not only essential for the initial ATP-dependent activation of ubiquitin in the ubiquitin degradtion pathway, but also capable of the catalytic extension of the polyubiquitin chain on a mono-ubiquitinated substrate
physiological function
-
in mouse embryo fibroblast cell A31N-ts20, which is thermosensitive for ubiquitin-activating enzyme E1, the enzymatic activity of the enzyme is heat-inactivatable in vitro; and a major mechanism responsible for E1 inactivation in vivo consists of accelerated destruction. In vivo, ubiquitination of the various protein substrates in A31N-ts20 cells requires different amounts of E1 enzyme
physiological function
isoform Uba6 forms a covalent link with ubiquitin in vitro and in vivo, which is sensitive to reducing conditions. In an in vitro polyubiquitylation assay, recombinant Uba6 can activate ubiquitin and transfer it onto the ubiquitin-conjugating enzyme UbcH5B. Ubiquitin activated by Uba6 can be used for ubiquitylation of p53 by MDM2 and supports the autoubiquitylation of the E3 ubiquitin ligases HectH9 and E6-AP
physiological function
-
comparative proteomic analysis of wild-type and SAP domain-mutant Foot-and-mouth disease virus-infected porcine cells identifies the ubiquitin-activating enzyme UBE1 required for virus replication. Overexpression of the enzyme UBE1 enhances the replication of the virus, and knockdown of UBE1 decreases virus replication. te virus manipulates UBE1 for increased viral replication, and the SAP domain is involved in this process, overview
physiological function
-
ubiquitin-activating enzyme 1 does not act as a second E1 activating enzyme for ubiquitin-like modifier HLA-F adjacent transcript but FAT10ylation of UBE1 leads to its proteasomal degradation
physiological function
enzyme E1 is an essential gene for parasite viability and is implicated in encystation.Enzyme overexpression greatly increases the encystation rate, indicating a relationship between E1 and Giardia differentiation
physiological function
ubiquitin-activating enzyme (E1) is a key regulator in protein ubiquitination, which lies on the upstream of the ubiquitin-related pathways and determines the activation of the downstream enzyme cascade
physiological function
-
UBE1s catalyze the first steps in the ubiquitin conjugation cascade and are potentially involved in compatible pollination and ubiquitinmediated S-RNase degradation
physiological function
UBA6 is the specific E1 that activates FAT10 and USE1 (also known as UBE2Z), an E2-conjugating enzyme that interacts exclusively with UBA6, accepts both ubiquitin and FAT10 from UBA6. UBA6 is one of the eight known E1 ubiquitin-activating enzymes and is the only E1 enzyme that can activate both ubiquitin and ubiquitin-like protein HLA-F adjacent transcript 10 (FAT10). In eukaryotic cells, the post-translational modification of proteins by ubiquitin or ubiquitin-like proteins (UBLs) is the most common trigger for protein degradation and is involved in the regulation of a wide range of biological processes. FAT10 (HLA-F-adjacent transcript 10), which belongs to the UBL family, is activated specifically through the UBA6-USE1 cascade and targets substrates covalently for 26S proteasomal degradation. The E1 ubiquitin-activating enzyme interacts with LMO2, a well-recognized transcriptional regulator in hematopoietic and endothelial systems, that is involved in the regulatory hierarchy of UBA6-USE1-FAT10ylation pathway by targeting the E1 enzyme UBA6
physiological function
ubiquitin-activating enzyme (E1) activates ubiquitin (Ub) conjugating enzyme (E2)
physiological function
the ubiquitin-activating enzyme E1 (UBA1) plays a critical role in protein degradation and in pathological processes. UBA1 participates the development of vascular restenosis
physiological function
ubiquitination is the process of covalent conjugation of ubiquitin (UB) to cellular proteins mediated by E1 (UB activating enzyme)-E2 (UB conjugating enzyme)-E3 (UB ligase) enzyme cascade. Ubiquitination plays critical roles in various diseases including cancer. E1 catalyzes the formation of the thioester bond between the C-terminus of UB and the active site cysteine of E1 in presence of ATP, initiating UB transfer to E2 and subsequently to target proteins that are recruited by E3. The non-canonical ubiquitin activating enzyme UBA6 suppresses epithelial-mesenchymal transition of mammary epithelial cells. Ubiquitination pathways initiated specifically by UBA6 set a suppressive barrier against critical steps of mammary carcinogenesis such as loss of polarity, anoikis resistance and epithelial-mesenchymal transition (EMT). The Rho-GTPase CDC42 is one of the specific targets of UBA6-initiated ubiquitination and plays a key role in the function of UBA6 in controlling epithelial homeostasis, since a CDC42 inhibitor, ML141, rescues UBA6-deficient cells from the EMT phenotype. UBA6 is low or undetectable in a substantial population of invasive breast cancer tissues, suggesting the cancer-associated roles for the non-canonical E1
physiological function
protein ubiquitination is mediated sequentially by ubiquitin activating enzyme E1, ubiquitin conjugating enzyme E2 and ubiquitin ligase E3. Ezrin and CUGBP1 undergo Uba6-dependent polyubiquitination. Uba1 is not required, in contrast to Uba6, for polyubiquitination and proteasomal degradation of ezrin and CUGBP1. Distinctive substrate pools exist for Uba1 and Uba6 that reflect non-redundant biological roles for Uba6
physiological function
protein ubiquitination is mediated sequentially by ubiquitin activating enzyme E1, ubiquitin conjugating enzyme E2 and ubiquitin ligase E3. Polyubiquitination and proteasomal degradation of ezrin and CUGBP1 require Uba6, but not Uba1. Ezrin and CUGBP1 undergo Uba6-dependent polyubiquitination. Uba6 is involved in the control of ezrin localization and epithelial morphogenesis. Distinctive substrate pools exist for Uba1 and Uba6 that reflect non-redundant biological roles for Uba6
physiological function
A0A6P7D3I5
early pregnancy reduces expression of UBE1L in maternal thymus, which may participate in regulation of maternal immune tolerance during early pregnancy in sheep
physiological function
ubiquitin-activating enzyme (E1) is the first enzyme of the ubiquitination pathway and is required to activate ubiquitin. E1 along with other enzymes plays a role in the regulation of cell cycle proteins like histone H2A and p53, which are essential for cell cycling
physiological function
the enzyme regulates the ubiquitin conjugation cascade
physiological function
the enzyme (Uba6) initiates signal transduction by activating ubiquitin and the ubiquitin-like protein FAT10 in a two-step process involving sequential catalysis of adenylation and thioester bond formation
physiological function
ubiquitin-activating enzyme (E1) is the first enzyme of the ubiquitination pathway and is required to activate ubiquitin. The SCCH domain and to some extent the ubiquitin fold domain (UFD) apparently interfere with cellular functions such as survival under various stresses
physiological function
UBA1 is essential for autophagy in certain cell types
physiological function
-
ubiquitin-activating enzyme (E1) is the first enzyme of the ubiquitination pathway and is required to activate ubiquitin. E1 along with other enzymes plays a role in the regulation of cell cycle proteins like histone H2A and p53, which are essential for cell cycling
-
physiological function
-
ubiquitin-activating enzyme (E1) is the first enzyme of the ubiquitination pathway and is required to activate ubiquitin. The SCCH domain and to some extent the ubiquitin fold domain (UFD) apparently interfere with cellular functions such as survival under various stresses
-
physiological function
Giardia duodenalis ATCC 50803
-
enzyme E1 is an essential gene for parasite viability and is implicated in encystation.Enzyme overexpression greatly increases the encystation rate, indicating a relationship between E1 and Giardia differentiation
-
additional information
-
conjugation of the ubiquitin activating enzyme UBE1 with the ubiquitin-like modifier FAT10 targets it for proteasomal degradation. UBE1 uses Cys632 in the active site
additional information
-
the enzyme has six ATP binding sites, one catalytic residue, and one E2 binding domain
additional information
UBA5 is the smallest and structurally simplest E1. The active site Cys of UBA5 (Cys 250) is located within the adenylation domain, but this domain is not sufficient for the formation of a thioester bond between the UFM1 C terminus and the UBA5 catalytic Cys. Modeling of a cis-binding mechanism of UFM1 to UBA5. Trans-binding mechanism of UFM1 transfer to the E2, UFC1. Homodimerization of UBA5 is essential for activating UFM1
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
119600
x * 12000 and x * 124000, SDS-PAGE, x * 119600, calculated
12000
x * 12000 and x * 124000, SDS-PAGE, x * 119600, calculated
124000
x * 12000 and x * 124000, SDS-PAGE, x * 119600, calculated
130000
-
recombinant His6-tagged chimeric mutant Aos1-Uba2 SUMO-E1 enzyme mAU, gel filtration
47000
1 * 68000 + 1 * 47000, the enzyme is proteolytically processed mainly into two fragments of 68 kDa (N-terminal) and 47 kDa (C-terminal)
68000
1 * 68000 + 1 * 47000, the enzyme is proteolytically processed mainly into two fragments of 68 kDa (N-terminal) and 47 kDa (C-terminal)
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
homodimer
dimerization of UBA5 is required for UFM1 activation. The active site Cys of UBA5 (Cys 250) is located within the adenylation domain
monomer
additional information
?
x * 12000 and x * 124000, SDS-PAGE, x * 119600, calculated
dimer
1 * 68000 + 1 * 47000, the enzyme is proteolytically processed mainly into two fragments of 68 kDa (N-terminal) and 47 kDa (C-terminal)
dimer
Giardia duodenalis ATCC 50803
-
1 * 68000 + 1 * 47000, the enzyme is proteolytically processed mainly into two fragments of 68 kDa (N-terminal) and 47 kDa (C-terminal)
-
dimer
analytical ultracentrifugation analysis, forms primarily dimers with 1.85:1 dimers to monomers ratio
monomer
analytical ultracentrifugation analysis, forms primarily dimers with 1.85:1 dimers to monomers ratio
additional information
the enzyme N-terminal domains contain inactive adenylation domain (IAD) and the first catalytic cysteine half-domain (FCCH). The IAD domain covers from Met1 to Glu204 and Val295 to Ile439 and that the FCCH domain covers from Glu205 to Gln294. The structure of ubiquitin E1 consists of four different domain blocks, overview. The enzyme forms a pseudo-dimer
additional information
-
the enzyme N-terminal domains contain inactive adenylation domain (IAD) and the first catalytic cysteine half-domain (FCCH). The IAD domain covers from Met1 to Glu204 and Val295 to Ile439 and that the FCCH domain covers from Glu205 to Gln294. The structure of ubiquitin E1 consists of four different domain blocks, overview. The enzyme forms a pseudo-dimer
additional information
the structure of E1 is organised into six domains namely, inactive adenylation domain (IAD), first catalytic cysteine half-domain (FCCH), four-helix bundles (4HB), active adenylation domain (AAD), second catalytic cysteine half-domain (SCCH) and Ub fold domain (UFD). E1 displays complex architecture due to the discontinuous and interspersed organisation of its six domains. The domains carrying the catalytic cysteine exist as two parts namely, FCCH and SCCH, which are found inserted into each of the adenylation domains. SCCH domain consisting of catalytic cysteine forms a thioester bond with ubiquitin. On the other hand FCCH, which associates with IAD is non-functional. 4HB domain present immediately after the FCCH, represents the second insertion in the IAD. UFD present in the C-terminus of E1 has a role in the recruitment of specific E2s to the ubiquitination pathway. Secondary structure analysis of enzyme domains, overview
additional information
-
the structure of E1 is organised into six domains namely, inactive adenylation domain (IAD), first catalytic cysteine half-domain (FCCH), four-helix bundles (4HB), active adenylation domain (AAD), second catalytic cysteine half-domain (SCCH) and Ub fold domain (UFD). E1 displays complex architecture due to the discontinuous and interspersed organisation of its six domains. The domains carrying the catalytic cysteine exist as two parts namely, FCCH and SCCH, which are found inserted into each of the adenylation domains. SCCH domain consisting of catalytic cysteine forms a thioester bond with ubiquitin. On the other hand FCCH, which associates with IAD is non-functional. 4HB domain present immediately after the FCCH, represents the second insertion in the IAD. UFD present in the C-terminus of E1 has a role in the recruitment of specific E2s to the ubiquitination pathway. Secondary structure analysis of enzyme domains, overview
additional information
-
the structure of E1 is organised into six domains namely, inactive adenylation domain (IAD), first catalytic cysteine half-domain (FCCH), four-helix bundles (4HB), active adenylation domain (AAD), second catalytic cysteine half-domain (SCCH) and Ub fold domain (UFD). E1 displays complex architecture due to the discontinuous and interspersed organisation of its six domains. The domains carrying the catalytic cysteine exist as two parts namely, FCCH and SCCH, which are found inserted into each of the adenylation domains. SCCH domain consisting of catalytic cysteine forms a thioester bond with ubiquitin. On the other hand FCCH, which associates with IAD is non-functional. 4HB domain present immediately after the FCCH, represents the second insertion in the IAD. UFD present in the C-terminus of E1 has a role in the recruitment of specific E2s to the ubiquitination pathway. Secondary structure analysis of enzyme domains, overview
-
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
additional information
-
conjugation of the ubiquitin activating enzyme UBE1 with the ubiquitin-like modifier FAT10 targets it for proteasomal degradation
proteolytic modification
the enzyme is proteolytically processed mainly into two fragments of 68 kDa (N-terminal) and 47 kDa (C-terminal)
proteolytic modification
Giardia duodenalis ATCC 50803
-
the enzyme is proteolytically processed mainly into two fragments of 68 kDa (N-terminal) and 47 kDa (C-terminal)
-
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structure of a human Uba6/ubiquitin complex, crystals are flash-frozen in liquid nitrogen
enzyme exists in two splice variants. To obtain high resolution crystals of UBA5, the N-terminal region of the long isoform, residues 156, are deleted and residues 330404 of the C-terminal domain are also removed. The removal of the CTD thus does not abrogate formation of the UBA5-UFM1 thioester intermediate. Crystals to 2.0 A resolution, and molecular replacement based on PDB structure 1ZFN. Structure shows similarities to both E1 and E1-like enzymes and is composed of an ATP-binding domain that consists of an eight-stranded beta-sheet surrounded by seven alpha-helices. UBA5 maintains a zinc-binding site that is coordinated by four cysteines with tetrahedral geometry
molecular modelling based on the crystal structure of Saccharomyces cerevisiae E1 and Mus musculus E1 and molecular dynamics simulation in water of the human E1-Ub complex
purified recombinant N-terminal enzyme domains comprising residues 1-439, hanging drop vapor diffusion method, mixing of 0.0015 ml of 15 mg/ml protein in 10mM Tris-HCl, pH 8.0, 150mM NaCl, and 2 mM DTT, with 0.0015 ml of reservoir solution containing 0.1 M Na3-citrate, pH 5.6, and 3.2 M NH4Ac, microseeding, 3 days, 21°C, X-ray diffraction structure determination and analysis at 2.75 A resolution
purified UBA5-UFM1 complex, containing both the adenylation domain and the UIS of UBA5, X-ray diffraction structure determination and analysis at 1.85-2.10 A
to 2.0 A resolution using molecular replacement based on PDB entry 1ZFN. UBA5 structure shows similarities to both E1 and E1-like enzymes and is composed of an ATP-binding domain that consists of an eight-stranded beta-sheet surrounded by seven alpha-helices. UBA5 maintains a zinc-binding site that is coordinated by four cysteines with tetrahedral geometry
NMR structural studies of the first catalytic cysteine half domain FCCH, interaction studies of FCCH and the other catalytic E1 domain SCCH, second catalytic cysteine half-domain. The E1 has several domains, an adenylation domain, composed of an active and inactive adenylation subdomains, and a catalytic cysteine domain, and smaller accessory domains: a four helix bundle and a ubiquitin fold domain. NMR cannot detect interactions between the FCCH and ubiquitin, or betweenween FCCH and SCCH if they are on separate poypeptide chains
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
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D290K/C250A
in this heterodimer, the UBA5 subunit that can form the thioester bond with UFM1 is missing the UFC1 binding site. In the UBA5 (D290K)-UBA5 (K271D/C250A DELTADUIS) heterodimer, binding to the UIS and charging can only take place on the same monomer, thereby supporting a cis-binding mechanism
D576A
D576E
D576N
K528A
A189T
-
improved stability and activity compared to mutant A189T/W714C, but when incubated at 39°C, cells expressing the mutant show increased apoptotic rate ompared to wild-type. Mutant is able to monoubiquitinate histone H2A and to support growth of TS20 cells at 39°C. Compared to mutant A189T/W714C, mutation A189T significantly improves the ubiquitination-dependent disposal of HIF-1alpha
A189T/W714C
-
mutant protein is less stable than its wildtype counterpart, and restrictive temperature of 39°C accelerates its degradation
additional information
D576A
-
Km-value for ATP is 37.8fold higher than wild-type value, KM-value for ubiquitin is 36fold higher than wild-type value. kcat for ubiquitin adenylate formation is 250fold lower than wild-type value. kcat for ubiquitin carrier protein E2 transthiolation is 28.3fold lower than wild-type value
D576A
-
mutation within the MgATP2- binding site, results in dramatically impaired binding affinities for MgATP2-, a shift from ordered to random addition in co-substrate binding, and a significantly reduced rate of ternary complex formation that shifts the rate-limiting step to ubiquitin adenylate formation. Mutations does not affect the affinity of Ubc2b binding, however, differences in kcat values determined from ternary complex formation versus HsUbc2b transthiolation suggest that binding of the E2 enhances the rate of bound ubiquitin adenylate formation
D576E
-
Km-value for ATP is 4fold higher than wild-type value, KM-value for ubiquitin is 1.4fold higher than wild-type value. kcat for ubiquitin adenylate formation is 1200fold lower than wild-type value. kcat for ubiquitin carrier protein E2 transthiolation is 34fold lower than wild-type value
D576E
-
mutation within the MgATP2- binding site, results in dramatically impaired binding affinities for MgATP2-, a shift from ordered to random addition in co-substrate binding, and a significantly reduced rate of ternary complex formation that shifts the rate-limiting step to ubiquitin adenylate formation. Mutations does not affect the affinity of Ubc2b binding, however, differences in kcat values determined from ternary complex formation versus HsUbc2b transthiolation suggest that binding of the E2 enhances the rate of bound ubiquitin adenylate formation
D576N
-
Km-value for ATP is 5.2fold higher than wild-type value, KM-value for ubiquitin is 5fold higher than wild-type value. kcat for ubiquitin adenylate formation is 545fold lower than wild-type value. kcat for ubiquitin carrier protein E2 transthiolation is 155fold lower than wild-type value
D576N
-
mutation within the MgATP2- binding site, results in dramatically impaired binding affinities for MgATP2-, a shift from ordered to random addition in co-substrate binding, and a significantly reduced rate of ternary complex formation that shifts the rate-limiting step to ubiquitin adenylate formation. Mutations does not affect the affinity of Ubc2b binding, however, differences in kcat values determined from ternary complex formation versus HsUbc2b transthiolation suggest that binding of the E2 enhances the rate of bound ubiquitin adenylate formation
K528A
-
Km-value for ATP is 1.6fold higher than wild-type value, KM-value for ubiquitin is 2.9fold higher than wild-type value. kcat for ubiquitin adenylate formation is 400fold lower than wild-type value. kcat for ubiquitin carrier protein E2 transthiolation is 309fold lower than wild-type value
K528A
-
mutation within the MgATP2- binding site, results in dramatically impaired binding affinities for MgATP2-, a shift from ordered to random addition in co-substrate binding, and a significantly reduced rate of ternary complex formation that shifts the rate-limiting step to ubiquitin adenylate formation. Mutations does not affect the affinity of Ubc2b binding, however, differences in kcat values determined from ternary complex formation versus HsUbc2b transthiolation suggest that binding of the E2 enhances the rate of bound ubiquitin adenylate formation
additional information
-
a mutational reduction in Uba1 function (Uba1B2 mutation) reduces the efficacy of cell death, a complete loss of Uba1 function (Uba1A1 mutation) results in poor survival of mutant tissue and overgrowth of adjacent wild type tissue
additional information
-
mutagenesis of key residues of E1 reveals that its conserved catalytic cysteine residue is essential for the formation of these poyubiquitin chains. Inactivation of the ubiquitin-conjugating enzyme E2 has no effect on the ability of E1 to catalyze ubiquitin chain formation, suggesting E1 is not only responsible for the activaton of ubiquitin but also for the direct extension of the lysine 48-linked polyubiquitin chain by the direct transfer of the ubiquitin-thiolester from the active site of E1 to the terminal Lys48 of the growing chain
additional information
RNA antisense silencing of Giardia E1. Overexpression of E1 greatly increases the encystation rate
additional information
Giardia duodenalis ATCC 50803
-
RNA antisense silencing of Giardia E1. Overexpression of E1 greatly increases the encystation rate
-
additional information
removal of residues 330-404 of the C-terminal domain does not abrogate formation of the UBA5-ubiquitin fold modifier1 thioester intermediate, the UBA5 C-terminal domain is not required for adenylation or thioester transfer of ubiquitin fold modifier1 to the UBA5 catalytic cysteine
additional information
-
removal of residues 330-404 of the C-terminal domain does not abrogate formation of the UBA5-ubiquitin fold modifier1 thioester intermediate, the UBA5 C-terminal domain is not required for adenylation or thioester transfer of ubiquitin fold modifier1 to the UBA5 catalytic cysteine
additional information
MCF-10A cells stably expressing anti-UBA6 shRNA form similar structures as the wild-type cells, but also develop a number (about 5%) of tumor-like gigantic aggregates, approximately 30% of acini formed in the shUBA6 culture do not exhibit hollow lumen. UBA6 knockout cell phenotype, overview
additional information
-
MCF-10A cells stably expressing anti-UBA6 shRNA form similar structures as the wild-type cells, but also develop a number (about 5%) of tumor-like gigantic aggregates, approximately 30% of acini formed in the shUBA6 culture do not exhibit hollow lumen. UBA6 knockout cell phenotype, overview
additional information
enzyme silencing in HEK293 cells by lentiviral expression of shRNA. Generation of orthogonal pairs of xUB-xUBA6 and xUB-xUBA1, analysis of orthogonal interaction of xUB-xE1 in mammalian cells and identification of xUB-conjugated proteins. 697 potential Uba6 targets and 527 potential Uba1 targets with 258 overlaps are identified
additional information
enzyme silencing in HEK293 cells by lentiviral expression of shRNA. Generation of orthogonal pairs of xUB-xUBA6 and xUB-xUBA1, analysis of orthogonal interaction of xUB-xE1 in mammalian cells and identification of xUB-conjugated proteins. 697 potential Uba6 targets and 527 potential Uba1 targets with 258 overlaps are identified
additional information
-
construction of a mouse Aos1-Uba2 chimeric SUMO(small ubiquitin-related modifier)-E1 enzyme, mAU. The SUMO-E1 enzyme consists of two subunits, a heterodimer of activation of Smt3p 1 (Aos1) and ubiquitin activating enzyme 2 (Uba2), which resembles the N- and C-terminal halves of ubiquitin E1 (Uba1), the functional domains appear to be arranged in a fashion similar to Uba1. mAU has SUMO-E1 activity, indicating that mAU can be expressed in baculovirus-insect cells and represents a suitable source of SUMO-E1, enzymatic mechanism and structure of SUMO-E1, overview
additional information
-
isolation of a mutant in ubiquitin-activiting enzyme Uba1. The mutation alters sensitivity to various environmental stresses and reduces wild-type Uba1 protein function. Protein modification by ubiquitin is strongly impaired in the mutant, inhibiting degradation of ubiquitin-proteasome pathway substrates as well as ubiquitin-dependent but proteasome-independent degradation of membrane receptors
additional information
reduced survival rates of Saccharomyces cerevisiae strain MHY501 expressing the domains of ubiquitin-activating enzyme E1 under heat stress with or without inducer CuSO4, overview. Under antibiotic and heat stresses expression of the domains SCCH and UFD prove to be detrimental to cell survival
additional information
-
reduced survival rates of Saccharomyces cerevisiae strain MHY501 expressing the domains of ubiquitin-activating enzyme E1 under heat stress with or without inducer CuSO4, overview. Under antibiotic and heat stresses expression of the domains SCCH and UFD prove to be detrimental to cell survival
additional information
-
reduced survival rates of Saccharomyces cerevisiae strain MHY501 expressing the domains of ubiquitin-activating enzyme E1 under heat stress with or without inducer CuSO4, overview. Under antibiotic and heat stresses expression of the domains SCCH and UFD prove to be detrimental to cell survival
-
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-70°C, the storage of the recombinant mouse E1 does not result in a detectable denaturation of the enzyme
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
His6-tagged E1 expressed and purified in Saccharomyces cerevisiae MHY-501 cells
-
Ni-NTA column chromatography
recombinant enzyme, purification on Ni-NTA superflow sepharose and strep-tactin sepharose which is based on UB-UBE1 high-energy thioester bonded intermediate complex
recombinant FLAG-tagged wild-type and mutant enzmyes from Escherichia coli strain BL21 by affinity chromatography
recombinant GST-tagged enzyme from Hi5 insect cells by glutathione affinity chromatography, tag cleavage by thrombin, and gel filtration
-
recombinant His-tagged chimeric mutant Aos1-Uba2 SUMO-E1 enzyme mAU from insect cells by nickel affinity chromatography
-
recombinant His-tagged enzyme domains FCCH, 4HB, SCCH and UFD from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, incase of domain UFD purification containing 6 M urea, followed by dialysis, and ultrafiltration
recombinant His-tagged N-terminal enzyme domains from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, anion exchange chromatography, tag cleavage by 3C protease, another step of nickel affinity chromatography, followed by gel filtration
recombinant His-tagged wild-type and mutant enzmyes from Escherichia coli strain BL21 by nickel affinity chromatography
recombinant mRFP-enzyme from Escherichia coli strain DH5alpha by combined anion exchange/affinity chromatography and gel filtration
-
recombinant N-terminally His6-tagged enzyme UBA5 from Escherichia coli by nickel affinity chromatography
recombinant protein is purified by Ni-NTA His-Bind Superflow Sepharose and Strep-Tactin Sepahrose
recombinant protein, HIS-Select nickel affinity chromatography, further steps, ion exchange chromatography, followed by gel filtration
-
recombinant tagged full-length wild-type enzyme and truncated mutant versions from Escherichia coli by affinity chromatography
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
full length of human UBE1 is expressed in Escherichia coli via pET28b vector
gene CrUBE1, genotyping, DNA and amino acid sequence determination and analysis, sequence comparisons, semi-quantitative RT-PCR and quantitative real-time PCR enzyme expression anayses, recombinant expression in Pichia pastoris strain GS115
-
gene Uba1, recombinant expression of His-tagged wild-type and mutant enzmyes from in Escherichia coli strain BL21, recombinant coexpression FLAG-tagged pairs of an engineered ubiquitin and engineered Uba1 or Uba6, that are generated for exclusive interactions, in HEK-293 cells from lentiviral vectors, 697 potential Uba6 targets and 527 potential Uba1 targets with 258 overlaps are identified
gene UBA1, recombinant expression of isolated and His-tagged enzyme domains FCCH, 4HB, SCCH and UFD in Escherichia coli strain BL21(DE3)
gene Uba6, recombinant expression of His-tagged wild-type and mutant enzmyes from in Escherichia coli strain BL21, recombinant coexpression FLAG-tagged pairs of an engineered ubiquitin and engineered Uba1 or Uba6, that are generated for exclusive interactions, in HEK-293 cells from lentiviral vectors, 697 potential Uba6 targets and 527 potential Uba1 targets with 258 overlaps are identified
HEK293 cells are transiently co-transfected with expression plasmids for HA-UBE1, the HA-tagged active site cysteine mutant UBE1 C632A, a His3-FLAG-tagged FAT10, a His3-FLAG-tagged FAT10 mutant lacking a diglycine motif at the C-terminus, or a His3-FLAG-tagged lysine-less FAT10 mutant
-
His6-tagged E1 expressed and purified in Saccharomyces cerevisiae MHY-501 cells
-
overexpression of N-terminally or C-terminally HA-tagged enzyme in Giardia intestinalis trophozoites
recombinant baculovirus-mediated expression of the GST-tagged enzyme in Hi5 insect cells using the pFastBacHTA vector
-
recombinant expression of His6-tagged chimeric mutant Aos1-Uba2 SUMO-E1 enzyme mAU in Spodoptera frugiperda Sf9 insect cells via baculovirus transformation, mAU has SUMO-E1 activity. Recombinant expression of GST-tagged mAU in Escherichia coli
-
recombinant expression of mRFP-enzyme in Escherichia coli strain DH5alpha, linking of ubiquitin to the C-terminus of RFP through a peptide bond
-
recombinant expression of N-terminally His6-tagged enzyme UBA5 in Escherichia coli
recombinant expression of N-terminally His6-tagged N-terminal domains of the enzyme, residues 1-439, in Escherichia coli strain BL21(DE3) from vector pETDuet-1
recombinant transient overexpression of GST-tagged or Myc-tagged full-length wild-type enzyme and truncated mutant versions in HEK-293T cells, recombinant expression of UBA6 from pGEX-4T-1/pGEX4T-1-UBA6/pGEX4T-1-UFD plasmids in Escherichia coli
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the enzyme expression (both at mRNA and protein levels) is regulated during encystation
the enzyme expression (both at mRNA and protein levels) is regulated during encystation
the enzyme expression (both at mRNA and protein levels) is regulated during encystation
Giardia duodenalis ATCC 50803
-
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
the ubiquitin-activating enzyme E1 is a therapeutic target for the treatment of restenosis
medicine
synthesis
medicine
-
knockdown of E1 decreases the abundance of ubiquitinated proteins in leukemia and myeloma cells and induces cell death. Inhibitor 1-(3-chloro-4-fluorophenyl)-4-[(5-nitro-2-furyl)methylene]-3,5-pyrazolidinedione, i.e. PYZD-4409, induces cell death in malignant cells and preferentially inhibits the clonogenic growth of primary acute myeloid leukemia cells compared with normal hematopoietic cells. Mechanistically, genetic or chemical inhibition of E1 increases expression of E1 stress markers. ER membrane protein BI-1 overexpression blocks cell death after E1 inhibition
medicine
-
in a mouse model of leukemia, intraperitoneal administration of inhibitor 1-(3-chloro-4-fluorophenyl)-4-[(5-nitro-2-furyl)methylene]-3,5-pyrazolidinedione, i.e. PYZD-4409, decreases tumor weight and volume compared with control without untoward toxicity
medicine
-
functional foods, e.g. ginsenoside Rg1 in Panax ginseng root, targeting the ubiquitin-activating enzyme (E1) of the ubiquitin-proteasome pathway as anti-tumour agents are considered to be important for cancer chemoprevention
medicine
the ubiquitin-activating enzyme E1 is a therapeutic target for the treatment of restenosis
synthesis
expression of the full length of human UBE1 in Escherichia coli and purification by Ni-NTA superflow sepharose and strep-tactin sepharose which is based on UB-UBE1 high-energy thioester bonded intermediate complex. Purified UBE1 can activate and conjugate UB to ubiquitin-conjugating enzyme E2s
synthesis
-
510 mg of histidine-tagged mouse ubiquitin-activating enzyme E1 can be easily obtained from a 1 l Escherichia coli culture. A low temperature during the protein induction step is critical to obtain an active enzyme
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
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Arabidopsis thaliana (P92974), Arabidopsis thaliana (P93028), Arabidopsis thaliana
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Homo sapiens (P22314), Homo sapiens
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Mus musculus, Homo sapiens
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Homo sapiens
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Homo sapiens, Homo sapiens (A0AVT1), Mus musculus
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Proc. Natl. Acad. Sci. USA
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Homo sapiens
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Pfleger, C.M.; Harvey, K.F.; Yan, H.; Hariharan, I.K.
Mutation of the gene encoding the ubiquitin activating enzyme Uba1 causes tissue overgrowth in Drosophila
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1
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Drosophila melanogaster
brenda
Zheng, M.; Gu, X.; Zheng, D.; Yang, Z.; Li, F.; Zhao, J.; Xie, Y.; Ji, C.; Mao, Y.
UBE1DC1, an ubiquitin-activating enzyme, activates two different ubiquitin-like proteins
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104
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2008
Homo sapiens (Q9GZZ9)
brenda
Xu, G.W.; Ali, M.; Wood, T.E.; Wong, D.; Maclean, N.; Wang, X.; Gronda, M.; Skrtic, M.; Li, X.; Hurren, R.; Mao, X.; Venkatesan, M.; Beheshti Zavareh, R.; Ketela, T.; Reed, J.C.; Rose, D.; Moffat, J.; Batey, R.A.; Dhe-Paganon, S.; Schimmer, A.D.
The ubiquitin-activating enzyme E1 as a therapeutic target for the treatment of leukemia and multiple myeloma
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115
2251-2259
2010
Homo sapiens, Mus musculus
brenda
Bacik, J.P.; Walker, J.R.; Ali, M.; Schimmer, A.D.; Dhe-Paganon, S.
Crystal structure of the human ubiquitin-activating enzyme 5 (UBA5) bound to ATP: mechanistic insights into a minimalistic E1 enzyme
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285
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2010
Homo sapiens (Q9GZZ9), Homo sapiens
brenda
Brahemi, G.; Burger, A.M.; Westwell, A.D.; Brancale, A.
Homology modelling of human E1 ubiquitin activating enzyme
Lett. Drug Des. Discov.
7
57-62
2010
Homo sapiens (P22314), Homo sapiens
brenda
Zheng, M.; Liu, J.; Yang, Z.; Gu, X.; Li, F.; Lou, T.; Ji, C.; Mao, Y.
Expression, purification and characterization of human ubiquitin-activating enzyme, UBE1
Mol. Biol. Rep.
37
1413-1419
2010
Homo sapiens, Homo sapiens (Q712V1)
brenda
Huzil, J.T.; Pannu, R.; Ptak, C.; Garen, G.; Ellison, M.J.
Direct catalysis of lysine 48-linked polyubiquitin chains by the ubiquitin-activating enzyme
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282
37454-37460
2007
Escherichia coli
brenda
Jaremko, M.; Jaremko, L.; Nowakowski, M.; Wojciechowski, M.; Szczepanowski, R.H.; Panecka, R.; Zhukov, I.; Bochtler, M.; Ejchart, A.
NMR structural studies of the first catalytic half-domain of ubiquitin activating enzyme
J. Struct. Biol.
185
69-78
2014
Mus musculus (Q02053), Mus musculus
brenda
Carvalho, A.F.; Pinto, M.P.; Grou, C.P.; Vitorino, R.; Domingues, P.; Yamao, F.; Sa-Miranda, C.; Azevedo, J.E.
High-yield expression in Escherichia coli and purification ofmouse ubiquitin-activating enzyme E1
Mol. Biotechnol.
51
254-261
2012
Mus musculus
brenda
Salvat, C.; Acquaviva, C.; Scheffner, M.; Robbins, I.; Piechaczyk, M.; Jariel-Encontre, I.
Molecular characterization of the thermosensitive E1 ubiquitin-activating enzyme cell mutant A31N-ts20. Requirements upon different levels of E1 for the ubiquitination/degradation of the various protein substrates in vivo
Eur. J. Biochem.
267
3712-3722
2000
Mus musculus
brenda
Swanson, R.; Hochstrasser, M.
A viable ubiquitin-activating enzyme mutant for evaluating ubiquitin system function in Saccharomyces cerevisiae
FEBS Lett.
477
193-198
2000
Saccharomyces cerevisiae
brenda
Lu, X.; Olsen, S.K.; Capili, A.D.; Cisar, J.S.; Lima, C.D.; Tan, D.S.
Designed semisynthetic protein inhibitors of Ub/Ubl E1 activating enzymes
J. Am. Chem. Soc.
17
1748-1749
2010
Schizosaccharomyces pombe
brenda
Pickart, C.M.; Kasperek, E.M.; Beal, R.; Kim, A.
Substrate properties of site-specific mutant ubiquitin protein (G76A) reveal unexpected mechanistic features of ubiquitin-activating enzyme (E1)
J. Biol. Chem.
269
7115-7123
1994
Bos taurus
brenda
Lao, T.; Chen, S.; Sang, N.
Two mutations impair the stability and function of ubiquitin-activating enzyme (E1)
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227
1561-1568
2012
Mus musculus
brenda
Wee, K.E.; Lai, Z.; Auger, K.R.; Ma, J.; Horiuchi, K.Y.; Dowling, R.L.; Dougherty, C.S.; Corman, J.I.; Wynn, R.; Copeland, R.A.
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19
489-498
2000
Homo sapiens
brenda
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Crystal structure of UBA2ufd-Ubc9: Insights into E1-E2 interactions in Sumo pathways
PLoS ONE
1
e15805
2010
Saccharomyces cerevisiae (P52488), Saccharomyces cerevisiae
brenda
Nino, C.A.; Prucca, C.G.; Chaparro, J.; Lujan, H.D.; Wasserman, M.
The ubiquitin-activating enzyme (E1) of the early-branching eukaryote Giardia intestinalis shows unusual proteolytic modifications and play important roles during encystation
Acta Trop.
123
39-46
2012
Giardia duodenalis (A8BBP6), Giardia duodenalis ATCC 50803 (A8BBP6)
brenda
Nakayama, T.; Yuasa, E.; Kanemaru, A.; Saito, M.; Saitoh, H.
Construction of a mouse Aos1-Uba2 chimeric SUMO-E1 enzyme, mAU, and its expression in baculovirus-insect cells
Bioengineered
5
133-137
2014
Mus musculus
brenda
Xie, S.T.
Expression, purification, and crystal structure of N-terminal domains of human ubiquitin-activating enzyme (E1)
Biosci. Biotechnol. Biochem.
78
1542-1549
2014
Homo sapiens (P22314), Homo sapiens
brenda
Miao, H.X.; Qin, Y.H.; Ye, Z.X.; Hu, G.B.
Molecular characterization and expression analysis of ubiquitin-activating enzyme E1 gene in Citrus reticulata
Gene
513
249-259
2013
Citrus reticulata
brenda
Chang, T.; Huang, Y.; Ou, Y.
The role of ginsenosides in inhibiting ubiquitin activating enzyme (E1) activity
J. Funct. Foods
7
462-470
2014
Homo sapiens
-
brenda
Zhu, Z.; Yang, F.; Zhang, K.; Cao, W.; Jin, Y.; Wang, G.; Mao, R.; Li, D.; Guo, J.; Liu, X.; Zheng, H.
Comparative proteomic analysis of wild-type and SAP domain-mutant Foot-and-mouth disease virus (FMDV)-infected porcine cells identifies the ubiquitin-activating enzyme UBE1 required for virus replication
J. Proteome Res.
14
4194-4206
2015
Sus scrofa
brenda
Bialas, J.; Groettrup, M.; Aichem, A.
Conjugation of the ubiquitin activating enzyme UBE1 with the ubiquitin-like modifier FAT10 targets it for proteasomal degradation
PLoS ONE
10
e0120329
2015
Homo sapiens
brenda
Ungermannova, D.; Parker, S.J.; Nasveschuk, C.G.; Wang, W.; Quade, B.; Zhang, G.; Kuchta, R.D.; Phillips, A.J.; Liu, X.
Largazole and its derivatives selectively inhibit ubiquitin activating enzyme (E1)
PLoS ONE
7
e29208
2012
Homo sapiens, Schizosaccharomyces pombe
brenda
Liu, H.Y.; Pfleger, C.M.
Mutation in E1, the ubiquitin activating enzyme, reduces Drosophila lifespan and results in motor impairment
PLoS ONE
8
e32835
2013
Drosophila melanogaster
brenda
Qin, Z.; Cui, B.; Jin, J.; Song, M.; Zhou, B.; Guo, H.; Qian, D.; He, Y.; Huang, L.
The ubiquitin-activating enzyme E1 as a novel therapeutic target for the treatment of restenosis
Atherosclerosis
247
142-153
2016
Homo sapiens (P22314)
brenda
Wu, C.; Liu, Y.; Gu, X.; Zhu, T.; Yang, S.; Sun, W.
LMO2 blocks the UBA6-USE1 interaction and downstream FAT10ylation by targeting the ubiquitin fold domain of UBA6
Biochem. Biophys. Res. Commun.
478
1442-1448
2016
Homo sapiens (A0AVT1)
brenda
Oweis, W.; Padala, P.; Hassouna, F.; Cohen-Kfir, E.; Gibbs, D.R.; Todd, E.A.; Berndsen, C.E.; Wiener, R.
Trans-binding mechanism of ubiquitin-like protein activation revealed by a UBA5-UFM1 complex
Cell Rep.
16
3113-3120
2016
Homo sapiens (Q9GZZ9)
brenda
Lu, X.; Malley, K.R.; Brenner, C.C.; Koroleva, O.; Korolev, S.; Downes, B.P.
A MUB E2 structure reveals E1 selectivity between cognate ubiquitin E2s in eukaryotes
Nat. Commun.
7
12580
2016
Arabidopsis thaliana (P92974), Arabidopsis thaliana (P93028)
brenda
Liu, X.; Zhao, B.; Sun, L.; Bhuripanyo, K.; Wang, Y.; Bi, Y.; Davuluri, R.; Duong, D.; Nanavati, D.; Yin, J.; Kiyokawa, H.
Orthogonal ubiquitin transfer identifies ubiquitination substrates under differential control by the two ubiquitin activating enzymes
Nat. Commun.
8
14286
2017
Homo sapiens (P22314), Homo sapiens (A0AVT1)
brenda
Liu, X.; Sun, L.; Gursel, D.B.; Cheng, C.; Huang, S.; Rademaker, A.W.; Khan, S.A.; Yin, J.; Kiyokawa, H.
The non-canonical ubiquitin activating enzyme UBA6 suppresses epithelial-mesenchymal transition of mammary epithelial cells
Oncotarget
8
87480-87493
2017
Homo sapiens (A0AVT1), Homo sapiens
brenda
Zhang, L.; Zhao, Z.; Wang, Y.; Li, N.; Cao, N.; Yang, L.
Changes in expression of interferon-stimulated genes and ubiquitin activating enzyme E1-like in ovine thymus during early pregnancy
Anim. Reprod.
17
e20190134
2020
Ovis aries (A0A6P7D3I5), Ovis aries
brenda
Prabha, C.
Structural and functional characterisation of the domains of ubiquitin-activating enzyme (E1) of Saccharomyces cerevisiae
Cell Biochem. Biophys.
78
309-319
2020
Saccharomyces cerevisiae (P22515), Saccharomyces cerevisiae, Saccharomyces cerevisiae ATCC 204508 (P22515)
brenda
Borgo, C.; DAmore, C.; Capurro, V.; Tomati, V.; Sondo, E.; Cresta, F.; Castellani, C.; Pedemonte, N.; Salvi, M.
Targeting the E1 ubiquitin-activating enzyme (UBA1) improves elexacaftor/tezacaftor/ivacaftor efficacy towards F508del and rare misfolded CFTR mutants
Cell. Mol. Life Sci.
79
192
2022
Homo sapiens (P22314)
brenda
Lambert-Smith, I.; Saunders, D.; Yerbury, J.
The pivotal role of ubiquitin-activating enzyme E1 (UBA1) in neuronal health and neurodegeneration
Int. J. Biochem. Cell Biol.
123
105746
2020
Homo sapiens (P22314)
brenda
Yuan, L.; Gao, F.; Lv, Z.; Nayak, D.; Nayak, A.; Santos Bury, P.D.; Cano, K.E.; Jia, L.; Oleinik, N.; Atilgan, F.C.; Ogretmen, B.; Williams, K.M.; Davies, C.; El Oualid, F.; Wasmuth, E.V.; Olsen, S.K.
Crystal structures reveal catalytic and regulatory mechanisms of the dual-specificity ubiquitin/FAT10 E1 enzyme Uba6
Nat. Commun.
13
4880
2022
Homo sapiens (A0AVT1)
brenda
EXTERNAL LINKS (specific for EC-Number 6.2.1.45)
Transporter Classification Database (TCDB): 3.A.25.2.1
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