Information on EC 2.3.2.27 - RING-type E3 ubiquitin transferase and Organism(s) Homo sapiens

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The enzyme appears in selected viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.3.2.27
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RECOMMENDED NAME
GeneOntology No.
RING-type E3 ubiquitin transferase
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
protein ubiquitination
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SYSTEMATIC NAME
IUBMB Comments
[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine:[acceptor protein] ubiquitin transferase (isopeptide bond-forming; RING-type)
The RING domain of E3 ubiquitin transferase serves as a mediator bringing the ubiquitin-charged E2 ubiquitin-conjugating enzyme and the acceptor protein together to enable the direct transfer of ubiquitin through the formation of an isopeptide bond between the C-terminal glycine residue of ubiquitin an the epsilon-amino group of an L-lysine residue of the acceptor protein. The RING-E3 domain does not form a catalytic thioester intermediate with ubiquitin (unlike the HECT domain, EC 2.3.2.26). RING-type ubiquitin transferases may occur as single-chain enzymes but also in dimeric forms or in multi-subunit assemblies.
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2 [gp78-ubiquitin-carrier protein Ub2g2]-S-ubiquitinyl-L-cysteine
[gp78-ubiquitin-carrier protein Ub2g2]-S-[ubiquitinyl-N6-ubiquitinyl-L-lysine46]-L-cysteine
show the reaction diagram
use of mouse Ube2g2 ubiquitin conjugating enzyme. Ube2g2/gp78-mediated polyubiquitination involves preassembly of Lys 48-linked ubiquitin chains at the catalytic cysteine residue C89 of Ube2g2. The growth of Ube2g2-anchored ubiquitin chains seems to be mediated by an aminolysis-based transfer reaction between two Ube2g2 molecules that each carries a ubiquitin moiety in its active site. Polyubiquitination of a substrate can be achieved by transferring preassembled ubiquitin chains from Ube2g2 to a lysine residue in a substrate
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?
S-(ubiquitin)n-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [RNF186]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-(ubiquitin)n-[RNF186]-L-lysine
show the reaction diagram
BNip1 is a Bcl-2 family protein
isoform RNF186 undergoes RING-dependent self-ubiquitination
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?
S-(ubiquitin)n-[Ubc13]-L-cysteine + [ubiquitin]-L-lysine
[Ubc13]-L-cysteine + N6-(ubiquitin)n-[ubiquitin]-L-lysine
show the reaction diagram
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human T lymphotropic virus type 1 trans-activator/oncoprotein Tax greatly stimulates RNF8 and Ubc13:Uev1A/Uev2 to assemble long K63-polyubiquitin chains
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?
S-ubiquinyl-[UbcH13]-L-cysteine + [acceptor protein]-L-lysine
[UbcH13]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine
show the reaction diagram
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?
S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme Ubc13]-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme Ubc13]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine
show the reaction diagram
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?
S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme UbcH7]-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme UbcH7]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine
show the reaction diagram
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?
S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine
show the reaction diagram
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?
S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [BNip1]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[BNip1]-L-lysine
show the reaction diagram
BNip1 is a Bcl-2 family protein
BNip1 is polyubiquitinated by isoform RNF186 through K29 and K63 linkage in vivo. This modification promotes BNip1 transportation to mitochondria but has no influence on its protein level
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?
S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [histone H2A]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[histone H2A]-L-lysine
show the reaction diagram
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E3-ligase activity of isoform Ring1b on histone H2A is enhanced by polycomb group protein Bmi1 in vitro. The N-terminal Ring-domains are sufficient for this activity and Ring1a can replace Ring1b. E2 enzymes UbcH5a, b, c or UbcH6 support this activity with varying processivity and selectivity
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?
S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [Ring1b]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[Ring1b]-L-lysine
show the reaction diagram
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autoubiquitination reaction, E2 enzymes UbcH5a, b, c or UbcH6 support autoubiquitination
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?
S-ubiquitinyl-[Hip2]-L-cysteine + [acceptor protein]-L-lysine
[Hip2]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine
show the reaction diagram
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isoform RNF2 interacts with E2 protein Hip2, i.e. Huntingtin-interacting protein-2, and with Ubc4, UbcH5. RNF2 shows ubiquitin transferase E3 activity in the presence of Hip2
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?
S-ubiquitinyl-[Ubc7]-L-cysteine + [CYP3A4]-L-lysine
[Ubc7]-L-cysteine + N6-ubiquitinyl-[CYP3A4]-L-lysine
show the reaction diagram
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human liver endoplasmic reticulum-anchored cytochrome P450 enzyme CYP3A4 is degradedvia ubiquitylation by E2 ubiquitin-conjugating enzyme Ubc7/E3 ubiquitin-ligase gp78. CYP3A4 Asp/Glu/Ser(P)/Thr(P) surface clusters are important for its intermolecular electrostatic interactions with each of these E2-E3 subcomponents. By imparting additional negative charge to these Asp/Glu clusters, such Ser/Thr phosphorylation would generate P450 phosphodegrons for molecular recognition by the E2-E3 complexes, thereby controlling the timing of CYP3A4 ubiquitination and endoplasmic reticulum-associated degradation
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?
S-ubiquitinyl-[UbcH5a]-L-cysteine + [p53]-L-lysine
[UbcH5a]-L-cysteine + N6-ubiquitinyl-[p53]-L-lysine
show the reaction diagram
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?
S-ubiquitinyl-[UbcH5]-L-cysteine + [TRIM62]-L-lysine
[UbsH5B]-L-cysteine + N6-ubiquitinyl-[TRIM62]-L-lysine
show the reaction diagram
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TRIM62, in association with the E2 enzyme UbcH5B, catalyzes self-ubiquitination in vitro. The process requires an intact RING finger domain. The treatment of HEK-293T cells with a proteasome inhibitor stabilizes poly-ubiquitinated TRIM62, indicating that self-ubiquitination promotes the proteasomal degradation of TRIM62
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?
S-ubiquitinyl-[UbcM2]-L-cysteine + [acceptor protein]-L-lysine
[UbcM2]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine
show the reaction diagram
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?
[c-Cbl-ubiquitin-carrier protein]-S-ubiquitinyl-L-cysteine + [epidermal growth factor receptor]-L-lysine
[c-Cbl-ubiquitin-carrier protein]-L-cysteine + [epidermal growth factor receptor]-N6-ubiquitinyl-L-lysine
show the reaction diagram
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?
[CDC34]-S-ubiquitinyl-L-cysteine + [SCF]-L-lysine
[CDC34]-L-cysteine + [SCF]-N6-ubiquitinyl-L-lysine
show the reaction diagram
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acceptor protein SCF consists of the cullin Cul1, the RING subunit Rbx1/Roc1/Hrt1, the adaptor protein Skp1, and an F-box protein such as Skp2 or TrCP that binds substrates
the I44A mutation in ubiquitin profoundly inhibits its ability to serve as a donor for ubiquitin chain initiation or elongation, but can be rescued by compensatory mutations in the E2 Cdc34
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?
[gp78-ubiquitin-carrier protein Ub2g2]-S-(ubiquitin)x-L-cysteine + HERP-L-lysine
[gp78-ubiquitin-carrier protein Ub2g2]-L-cysteine + HERP-N6-(ubiquitin)x-L-lysine
show the reaction diagram
HERP, ER-associated, short-lived protein that interacts with several E3 enzymes. Use of mouse Ube2g2 ubiquitin conjugating enzyme. Ube2g2/gp78-mediated polyubiquitination involves preassembly of Lys 48-linked ubiquitin chains at the catalytic cysteine of Ube2g2. The growth of Ube2g2-anchored ubiquitin chains seems to be mediated by an aminolysis-based transfer reaction between two Ube2g2 molecules that each carries a ubiquitin moiety in its active site. Polyubiquitination of a substrate can be achieved by transferring preassembled ubiquitin chains from Ube2g2 to a lysine residue in a substrate
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[gp78-ubiquitin-carrier protein Ub2g2]-S-[ubiquitinyl-N6-ubiquitinyl-L-lysine46]-L-cysteine + x-2 [gp78-ubiquitin-carrier protein Ub2g2]-S-ubiquitinyl-L-cysteine
[gp78-ubiquitin-carrier protein Ub2g2]-S-(ubiquitin)x-L-cysteine
show the reaction diagram
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?
[PirH2-ubiquitin-carrier protein]-S-ubiquitinyl-L-cysteine + [PolH]-L-lysine
[PirH2-ubiquitin-carrier protein]-L-cysteine + [PolH]-N6-ubiquitinyl-L-lysine
show the reaction diagram
PolH, DNA polymerase eta, a Y family translesion polymerase and a target of the p53 tumor suppressor. PolH interacts with Pirh2 E3 ligase, via the polymerase-associated domain in PolH and the RING finger domain in Pirh2. PolH is recruited by Pirh2 and degraded by 20S proteasome in a ubiquitin-independent manner
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[RING-E3-ubiquitin-carrier protein TRIM25]-S-ubiquitinyl-L-cysteine + [RIG-I]-L-lysine
[RING-E3-ubiquitin-carrier protein TRIM25]-L-cysteine + [RIG-I]-N6-ubiquitinyl-L-lysine
show the reaction diagram
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the amino-terminal caspase recruitment domains CARDs of retinoic-acid-inducible gene RIG-I undergo robust ubiquitination induced by TRIM25 in mammalian cells. The carboxy-terminal SPRY domain of TRIM25 interacts with the N-terminal CARDs of RIG-I, this interaction effectively delivers the Lys 63-linked ubiquitin moiety to the N-terminal CARDs of RIG-I, resulting in a marked increase in RIG-I downstream signalling activity. The Lys 172 residue of RIG-I is critical for efficient TRIM25-mediated ubiquitination and for mitochondrial signaling protein MAVS binding, as well as the ability of RIG-I to induce antiviral signal transduction, the amino-terminal caspase recruitment domains CARDs of retinoic-acid-inducible protein RIG-I undergo robust ubiquitination induced by TRIM25 in mammalian cells. The carboxy-terminal SPRY domain of TRIM25 interacts with the N-terminal CARDs of RIG-I, this interaction effectively delivers the Lys 63-linked ubiquitin moiety to the N-terminal CARDs of RIG-I, resulting in a marked increase in RIG-I downstream signalling activity. The Lys 172 residue of RIG-I is critical for efficient TRIM25-mediated ubiquitination and for mitochondrial signaling protein MAVS binding, as well as the ability of RIG-I to induce antiviral signal transduction
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[RN181-ubiquitin-carrier protein]-S-ubiquitinyl-L-cysteine + [RN181]-L-lysine
[RN181-ubiquitin-carrier protein]-L-cysteine + [RN181]-N6-ubiquitinyl-L-lysine
show the reaction diagram
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in the presence of a ubiquitin-activating E1 enzyme, a ubiquitin-conjugating E2 enzyme, ubiquitin monomers and ATP, RN181 is self-ubiquitinated
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?
[RNF43-ubiquitin-carrier protein]-S-ubiquitinyl-L-cysteine + [RNF43]-L-lysine
[RNF43-ubiquitin-carrier protein]-L-cysteine + [RNF43]-N6-ubiquitinyl-L-lysine
show the reaction diagram
isoform RNF43 has autoubiquitylation activity. RNF43 is a RING finger-dependent E3 ligase that is selective for E2 enzymes UbcH5b and UbcH5c
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[TEB4-UBC7]-S-ubiquitinyl-L-cysteine + ubiquitin-L-lysine48
[TEB4-UBC7]-L-cysteine + ubiquitin-N6-ubiquitinyl-L-lysine48
show the reaction diagram
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formation of a ubiquitin dimer, where residue lysine48 is linked to the C-terminal carboxyl of another ubiquitin. The UBC7-dependent ubiquitin–ubiquitin linkage reaction requires the presence of the ubiquitin-activating enzyme E1 and ATP, suggesting that the activity requires the intermediate formation of an UBC7-ubiquitin thioester
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?
[TEB4-UBC7]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine
[TEB4-UBC7]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
show the reaction diagram
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the isolated TEB4 RING domain catalyses ubiquitin ligation in vitro in a reaction that is ubiquitin Lys48-specific and involves ubiquitin-conjugating enzyme UBC7
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?
[TRIM22-ubiquitin-carrier protein UbcH5B]-S-ubiquitinyl-L-cysteine + [TRIM22]-L-lysine
[TRIM22-ubiquitin-carrier protein UbcH5B]-L-cysteine + [TRIM22]-N6-ubiquitinyl-L-lysine
show the reaction diagram
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isoform undergoes self-ubiq­uitylation in vitro in combination with the E2 enzyme UbcH5B, the ubiq­uitylation is dependent on its RING finger domain. TRIM22 is conjugated with poly-ubiq­uitin chains and stabilized by proteasome inhibitor in 293T cells
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?
[TRIM5-ubiquitin-carrier protein UbcH5B]-S-ubiquitinyl-L-cysteine + [TRIM5]-L-lysine
[TRIM5-ubiquitin-carrier protein UbcH5B]-L-cysteine + [TRIM5]-N6-ubiquitinyl-L-lysine
show the reaction diagram
TRIM5 functions as a RING-finger-type E3 ubiquitin ligase both in vitro and in vivo and ubiquitinates itself in cooperation with the E2 ubiquitin-conjugating enzyme UbcH5B. TRIM5 is monoubiquitinated, and ubiquitination does not lead to proteasomal degradation. Monoubiquitination may be a signal for TRIM5 to translocate from cytoplasmic bodies to the cytoplasm
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additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme Ubc13]-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme Ubc13]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine
show the reaction diagram
O76064
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?
S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme UbcH7]-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme UbcH7]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine
show the reaction diagram
Q9Y4X5
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?
S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine
show the reaction diagram
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?
[RING-E3-ubiquitin-carrier protein TRIM25]-S-ubiquitinyl-L-cysteine + [RIG-I]-L-lysine
[RING-E3-ubiquitin-carrier protein TRIM25]-L-cysteine + [RIG-I]-N6-ubiquitinyl-L-lysine
show the reaction diagram
Q14258
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the amino-terminal caspase recruitment domains CARDs of retinoic-acid-inducible gene RIG-I undergo robust ubiquitination induced by TRIM25 in mammalian cells. The carboxy-terminal SPRY domain of TRIM25 interacts with the N-terminal CARDs of RIG-I, this interaction effectively delivers the Lys 63-linked ubiquitin moiety to the N-terminal CARDs of RIG-I, resulting in a marked increase in RIG-I downstream signalling activity. The Lys 172 residue of RIG-I is critical for efficient TRIM25-mediated ubiquitination and for mitochondrial signaling protein MAVS binding, as well as the ability of RIG-I to induce antiviral signal transduction
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additional information
?
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Parkin E3 ligase has autoubiquitination activity
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
ubiquitination in the platelet is modulated by elevated intracellular calcium level
Zinc
two Zn2+-binding sites are present involving four cysteine residues found in the loops between beta1-beta2 and beta3-beta4 at site I, residues C344, C347, C362, C367, and three cysteines and a histidine in the extended loop after beta4 at site II, residues C372, C375, H382, C389
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
ATP
presence of ATP is required for catalysis
PINK1
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Parkin activation as an E3 ubiquitin ligase is regulated by PTEN-induced putative kinase 1
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
sequence contains 13 predicted transmembrane domains. The N-terminal region of TEB4 is located in the cytoplasm, whereas the C-terminus of TEB4 has a luminal deposition
Manually annotated by BRENDA team
additional information
isoform TEB4 is notexpressed at the cell surface
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Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
UNIPROT
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
97000
x * 97000, SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 97000, SDS-PAGE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
the E3 ubiquitin ligase activity of isoform c-Cbl is negatively regulated by other domains present in the amino-terminal half of the protein, i.e. the TKB and linker helix domains, and this negative regulation is removed when the protein is phosphorylated on tyrosine residues. Tyrosine phosphorylation alters the conformation of c-Cbl. Mutation of certain conserved tyrosine residues to glutamate can constitutively activate the E3 activity of c-Cbl
ubiquitination
additional information
enzyme is N-terminally mono-ubiquitinated by the ubiquitin conjugating enzyme Ubc16
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystallization of isoform parkin protein residues 141-465 including RING 0 and RING-between-RING domains. The protein is assembled into two compact domain groups separated by linkers. The catalytic network consists of residues C431 and H433. Parkin functions as a RING/HECT hybrid ubiquitin ligase
hanging drop vapor diffusion method, using either 1.0-1.4 M potassium/sodium tartrate /0.1M CHES pH 9.5 /0.2M LiSO4, or 0.5-0.55 M trisodium citrate/0.1 M citric acid pH 5.2/0.2 M lithium acetate, at room temperature
heterodimeric structure of the complex of Ring1b and Bmi1. Complex formation depends on an N-terminal arm of Ring1b that embraces the Bmi1 Ring-domain. Catalytic activity resides in Ring1b and not in Bmi1
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in complex with polycomb group RING finger proteins PCGF5 or PCGF4 and E2 enzyme UbcH5. RING1B binds directly to UbcH5c, with the PCGF partner making no contacts with the E2. The catalytically critical hydrogen bond between RING1B R91 and the backbone carbonyl of UbcH5c Q92 is present in both the structures, consistent with an activated conformation of the E2. Differences between the PCGF4 and PCGF5 ternary complex structures are found at the N termini of the PCGF and RING1B
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RNF8(345-485)/Ubc13-Ub complex, hanging drop vapor diffusion method, using
solution structure of the isoform HHARI RING2 domain, the key portion of this E3 ligase required for the RING/HECT hybrid mechanism. The domain possesses two Zn2+-binding sites and a single exposed cysteine used for ubiquitin catalysis. A structural comparison of the RING2 domain with the HECT E3 ligase NEDD4 reveals a near mirror image of the cysteine and histidine residues in the catalytic site. A tandem pair of aromatic residues exists near the C-terminus of the HHARI RING2 domain that is conserved in other RING-in-Between-RING E3 ligases
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in HEK-293T and HeLa cells
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expression in COS-7 cell and 293-T cell
expression in Escherichia coli
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expression in HEK-293T cell
expression in HEK-293T cell and HBL human melanoma cell
expression in HeLa cells
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
human melanoma cells express four MGRN isoforms
TEB4 expression does not increase in response to the various stress conditions
the gene encoding RNF43 is upregulated in colon adenocarcinoma as well as in colon adenoma
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A46P
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the mutant shows barely detectable autoubiquitination activity compared to the wild type
C11A
mutation introduced to reduce the stability of the RING domain, poor activity
C15A
mutation in the conserved RING-finger domain, loss of autoubiquitination ability
C431A
mutation eliminates parkin-catalyzed degradation of mitochondria
C61A/C64A
mutation of two adjacent cysteine residues at the conserved zinc-binding position, mutant shows weak activity
C9A
mutation within the RING domain of TEB4, strongly impairs its own degradation
D67E
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mutation identified in Thai familial breast cancer patients. The mutation is located in the vicinity of Zn2+ binding site II. The D67E BRCA1 RING protein assumes a preformed structure in the absence of Zn2+. The Zn2+-bound mutant protein is more folded than wild-type, resulting in enhanced proteolytic resistance and dimerization. The mutation retains Zn2+ binding, and barely perturbs the native global structure of the BRCA1 RING domain. The D67E mutation might be a neutral or mild cancer-risk modifier of other defective mechanisms underlying BRCA1-mutation-related breast cancer
I53A
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the Ring1b/Bmi1 complex with an I53A mutation in Ring1b has almost no catalytic activity
K27N
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the mutant shows barely detectable autoubiquitination activity compared to the wild type
K48A
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the mutant has higher autoubiquitination activity than the wild type
L451D
the mutation causes a drastic decrease in the ability of the enzyme to stimulate Ubc13
R33Q
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the mutant shows barely detectable autoubiquitination activity compared to the wild type
R42P
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the mutant has higher autoubiquitination activity than the wild type
R441A
the mutation has little effect on the enzyme activity
S17D
phosphomimetic mutation, stimulates MDM2-mediated polyubiquitination of p53. The stimulation is independent of p53 substrate. Mutation alters the conformation of the isolated N-terminus, it induces increased thermostability of the isolated N-terminal domain, it stimulates the allosteric interaction of MDM2 with the DNA-binding domain of p53 and it stimulates a protein-protein interaction with the E2-ubiquitin complex in the absence of substrate p53 that, in turn, increases hydrolysis of the E2-ubiquitin thioester bond
T240R
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the mutant shows barely detectable autoubiquitination activity compared to the wild type
Y268E
no increased activity compared to unphosphorylated wild-type
Y268F
residue Y268 is not required for phosphorylation-induced activation
Y274E
slightly increased activity compared to unphosphorylated wild-type
Y291E
no increased activity compared to unphosphorylated wild-type
Y307E
strongly increased activity compared to unphosphorylated wild-type
Y337E
strongly increased activity compared to unphosphorylated wild-type
Y371E
mutant shows constitutive E3 ubiquitin ligase activity while retaining the ability to bind epidermal growth factor receptor. The Y371E mutant also has altered protease sensitivity, resembling the proteolytic pattern seen with tyrosine-phosphorylated c-Cbl wild-type; strongly increased activity compared to unphosphorylated wild-type
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine