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Information on EC 2.3.2.31 - RBR-type E3 ubiquitin transferase and Organism(s) Homo sapiens and UniProt Accession P50876
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2.3.2.31 RBR-type E3 ubiquitin transferaseIUBMB Comments
RBR-type E3 ubiquitin transferases have two RING fingers separated by an internal motif (IBR, for In Between RING). The enzyme interacts with the CRL (Cullin-RING ubiquitin Ligase) complexes formed by certain RING-type E3 ubiquitin transferase (see EC 2.3.2.27), which include a neddylated cullin scaffold protein and a substrate recognition module. The RING1 domain binds an EC 2.3.2.23, E2 ubiquitin-conjugating enzyme, and transfers the ubiquitin that is bound to it to an internal cysteine residue in the RING2 domain, followed by the transfer of the ubiquitin from RING2 to the substrate . Once the substrate has been ubiquitylated by the RBR-type ligase, it can be ubiqutylated further using ubiquitin carried directly on E2 enzymes, in a reaction catalysed by EC 2.3.2.27. Activity of the RBR-type enzyme is dependent on neddylation of the cullin protein in the CRL complex [2,4]. cf. EC 2.3.2.26, HECT-type E3 ubiquitin transferase, EC 2.3.2.27, RING-type E3 ubiquitin transferase, and EC 2.3.2.32, cullin-RING-type E3 NEDD8 transferase.
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
hide(Overall reactions are displayed. Show all >>)
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=
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[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine
+
[acceptor protein]-L-lysine
=
[E2 ubiquitin-conjugating enzyme]-L-cysteine
+
[acceptor protein]-N6-ubiquitinyl-L-lysine
Synonyms
rnf31, rbr e3, triad1, rnf144a, arih2, rnf144b, rnf19a, rnf217, rnf19b, rbr-type e3, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ARIH1
HHARI
Parkin
RBR E3
RBX1
-
-
-
-
Triad1
SYSTEMATIC NAME
IUBMB Comments
[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine:acceptor protein ubiquitin transferase (isopeptide bond-forming; RBR-type)
RBR-type E3 ubiquitin transferases have two RING fingers separated by an internal motif (IBR, for In Between RING). The enzyme interacts with the CRL (Cullin-RING ubiquitin Ligase) complexes formed by certain RING-type E3 ubiquitin transferase (see EC 2.3.2.27), which include a neddylated cullin scaffold protein and a substrate recognition module. The RING1 domain binds an EC 2.3.2.23, E2 ubiquitin-conjugating enzyme, and transfers the ubiquitin that is bound to it to an internal cysteine residue in the RING2 domain, followed by the transfer of the ubiquitin from RING2 to the substrate [4]. Once the substrate has been ubiquitylated by the RBR-type ligase, it can be ubiqutylated further using ubiquitin carried directly on E2 enzymes, in a reaction catalysed by EC 2.3.2.27. Activity of the RBR-type enzyme is dependent on neddylation of the cullin protein in the CRL complex [2,4]. cf. EC 2.3.2.26, HECT-type E3 ubiquitin transferase, EC 2.3.2.27, RING-type E3 ubiquitin transferase, and EC 2.3.2.32, cullin-RING-type E3 NEDD8 transferase.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
[E2 ubiquitin-conjugating enzyme cullin-1]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme cullin-1]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
-
overall reaction for HHARI
-
-
?
[E2 ubiquitin-conjugating enzyme cullin-2]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme cullin-2]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
-
overall reaction for HHARI
-
-
?
[E2 ubiquitin-conjugating enzyme cullin-3]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme cullin-3]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
-
overall reaction for HHARI
-
-
?
[E2 ubiquitin-conjugating enzyme cullin-4A]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme cullin-4A]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
-
overall reaction for HHARI
-
-
?
[E2 ubiquitin-conjugating enzyme cullin-5]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme cullin-5]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
-
overall reaction for TRIAD1
-
-
?
[E2 ubiquitin-conjugating enzyme UbcH5C]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme UbcH5C]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
-
-
-
?
[E2 ubiquitin-conjugating enzyme UbcH5]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme UbcH5]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
overall reaction
-
-
?
[E2 ubiquitin-conjugating enzyme UBCH7]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme UBCH7]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
[E2 ubiquitin-conjugating enzyme UBCH7]-S-ubiquitinyl-L-cysteine + [SEC13-SEC31A]-L-lysine
[E2 ubiquitin-conjugating enzyme UBCH7]-L-cysteine + [SEC13-SEC31A]-N6-ubiquitinyl-L-lysine
-
-
-
?
[E2 ubiquitin-conjugating enzyme UBE2L3]-S-ubiquitinyl-L-cysteine + [Miro1]-L-lysine
[E2 ubiquitin-conjugating enzyme UBE2L3]-L-cysteine + [Miro1]-N6-ubiquitinyl-L-lysine
-
-
-
?
[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
overall reaction
-
-
?
[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [RBR-type E3 ubiquitin transferase]-L-cysteine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + [RBR-type E3 ubiquitin transferase]-S-ubiquitinyl-L-cysteine
-
-
-
?
[RBR-type E3 ubiquitin transferase]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine
[RBR-type E3 ubiquitin transferase]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
-
-
-
?
[E2 ubiquitin-conjugating enzyme UBCH7]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme UBCH7]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
-
-
-
?
[E2 ubiquitin-conjugating enzyme UBCH7]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme UBCH7]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
overall reaction
-
-
?
[E2 ubiquitin-conjugating enzyme UBCH7]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme UBCH7]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
overall reaction
-
-
?
[E2 ubiquitin-conjugating enzyme UBCH7]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme UBCH7]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
-
overall reaction for TRIAD1
-
-
?
additional information
?
-
-
the enzyme acts as a monoubiquitin conjugating enzyme for neddylated CUL3KLHL12-RBX1 substrate SEC13-SEC31A
-
-
?
additional information
?
-
the enzyme acts as a monoubiquitin conjugating enzyme for neddylated CUL3KLHL12-RBX1 substrate SEC13-SEC31A
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-
?
additional information
?
-
-
the enzyme-substrate-interaction is neddylation-dependent
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-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
[E2 ubiquitin-conjugating enzyme cullin-1]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme cullin-1]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
-
overall reaction for HHARI
-
-
?
[E2 ubiquitin-conjugating enzyme cullin-2]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme cullin-2]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
-
overall reaction for HHARI
-
-
?
[E2 ubiquitin-conjugating enzyme cullin-3]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme cullin-3]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
-
overall reaction for HHARI
-
-
?
[E2 ubiquitin-conjugating enzyme cullin-4A]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme cullin-4A]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
-
overall reaction for HHARI
-
-
?
[E2 ubiquitin-conjugating enzyme cullin-5]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme cullin-5]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
-
overall reaction for TRIAD1
-
-
?
[E2 ubiquitin-conjugating enzyme UbcH5]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme UbcH5]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
overall reaction
-
-
?
[E2 ubiquitin-conjugating enzyme UBCH7]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme UBCH7]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
overall reaction
-
-
?
[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [RBR-type E3 ubiquitin transferase]-L-cysteine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + [RBR-type E3 ubiquitin transferase]-S-ubiquitinyl-L-cysteine
-
-
-
?
[RBR-type E3 ubiquitin transferase]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine
[RBR-type E3 ubiquitin transferase]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
-
-
-
?
[E2 ubiquitin-conjugating enzyme UBCH7]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme UBCH7]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
overall reaction
-
-
?
[E2 ubiquitin-conjugating enzyme UBCH7]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme UBCH7]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
overall reaction
-
-
?
[E2 ubiquitin-conjugating enzyme UBCH7]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine
[E2 ubiquitin-conjugating enzyme UBCH7]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
-
overall reaction for TRIAD1
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
methyl (2E)-4-[(2-oxo-1,2,5,6,7,8-hexahydroquinoline-3-carbonyl)amino]but-2-enoate
labels RNF31 with proteome-wide selectivity and effectively inhibits linear polyubiquitin chain formation in vitro and in cells
methyl (2E)-4-[(2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta[b]pyridine-3-carbonyl)amino]but-2-enoate
compound labels RNF31 RBR at the active site cysteine residue C885 in a time- and concentration-dependent manner. It effectively penetrates mammalian cells to inhibit RNF31 and NF-kappaB activation
additional information
single-domain antibodies can modulate the activity of the E3 ligase HOIP and facilitate crystallization of its catalytic RBR domain. Single domain antibodies may inhibit most, if not all, ubiquitin linear chain formation with both E2 enzymes UbcH5C and UbcH7 equally, one group of antibodies has a small effect on the observed activity with UbcH5C, but drastically slows down linear chain formation with UbcH7
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
neddylated cullin-1-RBX1 activates auto-inhibited isoform HHARI
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
endogenous Parkin is activated in neuronal cell lines in response to mitochondrial depolarization
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
mitophagy is regulated by a positive ubiquitylation feedback loop in which the PINK1 kinase phosphorylates both ubiquitin and the E3 ubiquitin ligase parkin. This event recruits parkin to the mitochondria
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
isoform RNF144A interacts with poly(ADP-ribose) polymerase PARP1, a DNA repair protein, through its carboxy-terminal region containing the transmembrane domain, and targets PARP1 for ubiquitination and subsequent proteasomal degradation. Induced expression of RNF144A decreases PARP1 protein levels and renders breast cancer cells resistant to the clinical-grade PARP inhibitor olaparib. Knockdown of endogenous RNF144A increases PARP1 protein levels and enhances cellular sensitivity to olaparib
physiological function
physiological function
a short extension of ARIH1 RING1, Zn2+-loop II, acts as a steric wedge to disrupt closed E2-ubiquitin, resulting in open E2-ubiquitin that favors ubiquitin transfer to the E3 active site
physiological function
ARIH1 predominantly and extensively interacts with activated cullin-RING E3 enzymes and acts as a monoubiquitin conjugating enzyme for neddylated CUL3-RBX1 substrate SEC13-SEC31A. Efficient neddylated cullin-RING E3 substrate polyubiquitylation can be achieved by UBCH7-ARIH1-mediated priming and CDC34-mediated chain elongation
physiological function
miR-218 targets parkin and negatively regulates PINK1/parkin-mediated mitophagy. Overexpression of microRNA miR-218 reduces parkin mRNA levels, reducing protein content and deregulating the E3 ubiquitin ligase action. Following miR-218 overexpression, mitochondria result less ubiquitylated and the autophagy machinery fails to proceed with correct mitochondrial clearance
physiological function
parkin does not require an E2 enzyme for substrate ubiquitination, lysine selection, and polyubiquitin chain formation. Both phosphorylated ubiquitin and the ubiquitin-accepting substrate contribute to maximal ubiquitin conjugation turnover of phosphorylated parkin. Phosphorylated ubiquitin enhances the transthiolation step, whereas the substrate clears the phosphorylated parkin-ubiquitin thioester intermediate
physiological function
RING1 domains of HHARI promote open sate E2-ubiquitin conjugates. RING1 opening of E2-ubiquitin enforces ubiquitin transfer via the RING2 active site Cys. The hydrophobic surface of ubiquitin is required for transfer of ubiquitin to the RBR active site. Mutations that ablate ubiquitin binding to HHARI RING2 also decrease RBR ligase activity
physiological function
RING1 domains of RNF144 promote open sate E2-ubiquitin conjugates. RING1 opening of E2-ubiquitin enforces ubiquitin transfer via the RING2 active site Cys
physiological function
the activity of inactive parkin molecules can be stimulated by the presence of activated parkin molecules, molecules can function together to ligate ubiquitin
physiological function
the ubiquitin-associated domain-containing DCNL1 is monoubiquitylated when bound to cullin-RING E3 ubiquitin ligases.This monoubiquitylation depends on the cullin-RING E3 ubiquitin ligases-associated Ariadne RBR ligases TRIAD1 (ARIH2) andHHARI (ARIH1) and strictly requires the DCNL1's ubiquitin-associated domain
physiological function
the ubiquitin-associated domain-containing DCNL1 is monoubiquitylated when bound to cullin-RING E3 ubiquitin ligases.This monoubiquitylation depends on the cullin-RING E3 ubiquitin ligases-associated Ariadne RBR ligases TRIAD1 (ARIH2) andHHARI (ARIH1) and strictly requires the DCNL1's ubiquitin-associated domain. Autoubiquitylated TRIAD1 mediates binding to the ubiquitin-associated domain and subsequently promotes a single ubiquitin attachment to DCNL1. DCNL1 monoubiquitylation is required for efficient cullin-RING E3 ubiquitin ligase activity
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). R144A_HUMAN
292
1
32890
Swiss-Prot
Secretory Pathway (Reliability: 4)
PDB
SCOP
CATH
UNIPROT
ORGANISM
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
cocrystal structure of HOIP RBR domain with single-domain antibody, use as a platform for soaking of ligands that target the active site cysteine of HOIP
structure of a parkin-phosphoubiquitin complex. Phosphoubiquitin binding induces a movement in the IBR domain to reveal a cryptic ubiquitin binding site. Mutation of this site negatively impacts on Parkin's activity. Ubiquitin binding promotes cooperation between parkin molecules
structure of ARIH1 in complex with UbcH7-ubiquitin, to 3.2 A resolution. ARIH1 is autoinhibited even in the complex. The ARIH1 UBA-L domain binds to ubiquitin and NEDD8
structure of isoform HHARI, in complex with a UbcH7-ubiquitin thioester mimetic. Mechanistically important conformational changes in the RING1 and UBA-like domains of HHARI accompany UbcH7-ubiquitin binding. HHARI recruits E2-ubiquitin in an open conformation. HHARI optimally functions with UbcH7 that solely performs transthiolation, and HHARI prevents spurious discharge of ubiquitin from E2 to lysine residues by harboring structural elements that block E2-ubiquitin from adopting a closed conformation and participating in contacts to ubiquitin that promote an open E2-ubiquitin conformation
structure of the fully active HOIP-RBR in its transfer complex with an E2-ubiquitin conjugate. HOIP-RBR binds the E2-ubiquitin conjugate in an elongated fashion, with the E2 and E3 catalytic centers aligned for ubiquitin transfer, which structurally both requires and enables a HECT-like mechanism. Three distinct helix-IBR-fold motifs form ubiquitin-binding regions that engage the activated ubiquitin of the E2-ubiquitin conjugate as well as an additional regulatory ubiquitin molecule
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C431S/H433A
RING2 mutant, able to trap the catalytic parkin-ubiquitin intermediate
E321A/C431S/H433A
UBR2 patch mutant of parkin. In contrast to C431S/H433A, this mutant is defective in ubiquitin charging even in the presence of phosphoubiquitin
H302A/E321A/C431S/H433A
60fold reduced in ubiquitin charging of the RING2
T341N
mimic of mutant T415N in parkin, decreases HHARI's ligase activity substantially
additional information
additional information
-
mutants in ARIH1's UBA-to-RING1 helix, RING1, RING1-to-IBR helix, and RING2 domains display activity profile signatures corresponding to intrinsic RBR E3 activities of ubiquitin transfer from UBCH7 to ARIH1, alignment of the RING2 active site, and intrinsic ability of RING2 to mediate ligation
additional information
mutants in ARIH1's UBA-to-RING1 helix, RING1, RING1-to-IBR helix, and RING2 domains display activity profile signatures corresponding to intrinsic RBR E3 activities of ubiquitin transfer from UBCH7 to ARIH1, alignment of the RING2 active site, and intrinsic ability of RING2 to mediate ligation
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
GSH-Sepharose column chromatography, amylose resin column chromatography, and Ni2+-Sepharose column chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in HEK-293 cell
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
isoform RNF144A interacts with poly(ADP-ribose) polymerase PARP1 through its carboxy-terminal region containing the transmembrane domain, and targets PARP1 for ubiquitination and subsequent proteasomal degradation. Induced expression of RNF144A decreases PARP1 protein levels and renders breast cancer cells resistant to the clinical-grade PARP inhibitor olaparib. Knockdown of endogenous RNF144A increases PARP1 protein levels and enhances cellular sensitivity to olaparib
analysis
medicine
analysis
co-crystal structure of HOIP RBR domain with single-domain antibody, use as a platform for soaking of ligands that target the active site cysteine of HOIP
analysis
development of activity-based probes by reengineering of a ubiquitin-charged E2 conjugating enzyme using tosyl-substituted doubly activated genes and application in profiling the transthiolation activity of the RBR E3 ligase Parkin in vitro and in cellular extracts
analysis
development of chemical probes, ubiquitin C-terminal fluorescein thioesters UbMES and UbFluor, to qualitatively and quantitatively assess the activity of the RBR E3 ligase PARKIN in a simple experimental setup and in real time using fluorescence polarization. UbFluor quantitatively detects naturally occurring activation states of parkin caused by Ser65 phosphorylation and phosphorylated ubiquitin
medicine
parkin patient disease-associated mutation largely mediate their effect by altering transthiolation activity
medicine
upon infection, Trichinella spiralis secretes E2 Ub-conjugating protein UBE2L3, located in the secretory organ of the parasite during the muscle stages of infection. UBE2L3 but specifically binds to a panel of human RING E3 ligases, including the RBR E3 ARIH2 with which it interacts with a higher affinity than the mammalian ortholog UbcH7/UBE2L3. Expression of UBE2L3 in skeletal muscle cells causes a global downregulation in protein ubiquitination, most predominantly affecting motor, sarcomeric and extracellular matrix proteins, thus mediating their stabilization with regards to proteasomal degradation
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Scott, D.; Rhee, D.; Duda, D.; Kelsall, I.; Olszewski, J.; Paulo, J.; de Jong, A.; Ovaa, H.; Alpi, A.; Harper, J.; Schulman, B.
Two distinct types of E3 ligases work in unison to regulate substrate ubiquitylation
Cell
166
1198-1214
2016
Homo sapiens, Homo sapiens (Q9Y4X5)
-
Kelsall, I.; Duda, D.; Olszewski, J.; Hofmann, K.; Knebel, A.; Langevin, F.; Wood, N.; Wightman, M.; Schulman, B.; Alpi, A.
TRIAD1 and HHARI bind to and are activated by distinct neddylated Cullin-RING ligase complexes
EMBO J.
32
2848-2860
2013
Homo sapiens
Wenzel, D.; Lissounov, A.; Brzovic, P.; Klevit, R.
UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids
Nature
474
105-108
2011
Homo sapiens (P0ABD5)
Duda, D.; Olszewski, J.; Schuermann, J.; Kurinov, I.; Miller, D.; Nourse, A.; Alpi, A.; Schulman, B.
Structure of HHARI, a RING-IBR-RING ubiquitin ligase Autoinhibition of an Ariadne-family E3 and insights into ligation mechanism
Structure
21
1030-1041
2013
Homo sapiens (Q9Y4X5), Homo sapiens
Tsai, Y.I.; Johansson, H.; Dixon, D.; Martin, S.; Chung, C.W.; Clarkson, J.; House, D.; Rittinger, K.
Single-domain antibodies as crystallization chaperones to enable structure-based inhibitor development for RBR E3 ubiquitin ligases
Cell Chem. Biol.
27
83-93.e9
2020
Homo sapiens (Q96EP0)
Dove, K.K.; Stieglitz, B.; Duncan, E.D.; Rittinger, K.; Klevit, R.E.
Molecular insights into RBR E3 ligase ubiquitin transfer mechanisms
EMBO Rep.
17
1221-1235
2016
Homo sapiens, Homo sapiens (Q9Y4X5)
Di Rita, A.; Maiorino, T.; Bruqi, K.; Volpicelli, F.; Bellenchi, G.C.; Strappazzon, F.
miR-218 inhibits mitochondrial clearance by targeting PRKN E3 ubiquitin ligase
Int. J. Mol. Sci.
21
355
2020
Homo sapiens (O60260), Homo sapiens
Johansson, H.; Tsai, Y.; Fantom, K.; Chung, C.; Kaemper, S.; Martino, L.; Thomas, D.; Eberl, H.; Muelbaier, M.; House, D.; Rittinger, K.
Fragment-based covalent ligand screening enables rapid discovery of inhibitors for the RBR E3 ubiquitin ligase HOIP
J. Am. Chem. Soc.
141
2703-2712
2020
Homo sapiens (Q96EP0)
Park, S.; Foote, P.K.; Krist, D.T.; Rice, S.E.; Statsyuk, A.V.
UbMES and UbFluor Novel probes for ring-between-ring (RBR) E3 ubiquitin ligase PARKIN
J. Biol. Chem.
292
16539-16553
2017
Homo sapiens (O60260)
Kelsall, I.R.; Kristariyanto, Y.A.; Knebel, A.; Wood, N.T.; Kulathu, Y.; Alpi, A.F.
Coupled monoubiquitylation of the co-E3 ligase DCNL1 by Ariadne-RBR E3 ubiquitin ligases promotes cullin-RING ligase complex remodeling
J. Biol. Chem.
294
2651-2664
2019
Homo sapiens (O95376), Homo sapiens (Q9Y4X5)
Pao, K.C.; Stanley, M.; Han, C.; Lai, Y.C.; Murphy, P.; Balk, K.; Wood, N.T.; Corti, O.; Corvol, J.C.; Muqit, M.M.; Virdee, S.
Probes of ubiquitin E3 ligases enable systematic dissection of parkin activation
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2016
Homo sapiens (O60260)
Yuan, L.; Lv, Z.; Atkison, J.; Olsen, S.
Structural insights into the mechanism and E2 specificity of the RBR E3 ubiquitin ligase HHARI
Nat. Commun.
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211
2017
Homo sapiens (Q9Y4X5)
Kumar, A.; Chaugule, V.K.; Condos, T.E.C.; Barber, K.R.; Johnson, C.; Toth, R.; Sundaramoorthy, R.; Knebel, A.; Shaw, G.S.; Walden, H.
Parkin-phosphoubiquitin complex reveals cryptic ubiquitin-binding site required for RBR ligase activity
Nat. Struct. Mol. Biol.
24
475-483
2017
Homo sapiens (O60260)
Lechtenberg, B.C.; Rajput, A.; Sanishvili, R.; Dobaczewska, M.K.; Ware, C.F.; Mace, P.D.; Riedl, S.J.
Structure of a HOIP/E2~ubiquitin complex reveals RBR E3 ligase mechanism and regulation
Nature
529
546-550
2016
Homo sapiens (Q96EP0), Homo sapiens
Zhang, Y.; Liao, X.H.; Xie, H.Y.; Shao, Z.M.; Li, D.Q.
RBR-type E3 ubiquitin ligase RNF144A targets PARP1 for ubiquitin-dependent degradation and regulates PARP inhibitor sensitivity in breast cancer cells
Oncotarget
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94505-94518
2017
Homo sapiens (P50876), Homo sapiens
White, R.R.; Ponsford, A.H.; Weekes, M.P.; Rodrigues, R.B.; Ascher, D.B.; Mol, M.; Selkirk, M.E.; Gygi, S.P.; Sanderson, C.M.; Artavanis-Tsakonas, K.
Ubiquitin-dependent modification of skeletal muscle by the parasitic nematode, Trichinella spiralis
PLoS Pathog.
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Homo sapiens (O95376), Homo sapiens
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