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Information on EC 2.3.2.26 - HECT-type E3 ubiquitin transferase
for references in articles please use BRENDA:EC2.3.2.26
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EC Tree 2 Transferases
2.3 Acyltransferases
2.3.2 Aminoacyltransferases
2.3.2.26 HECT-type E3 ubiquitin transferase
IUBMB Comments
In the first step the enzyme transfers ubiquitin from the E2 ubiquitin-conjugating enzyme (EC 2.3.2.23) to a cysteine residue in its HECT domain (which is located in the C-terminal region), forming a thioester bond. In a subsequent step the enzyme transfers the ubiquitin to an acceptor protein, resulting in the formation of an isopeptide bond between the C-terminal glycine residue of ubiquitin and the ε-amino group of an L-lysine residue of the acceptor protein. cf. EC 2.3.2.27, RING-type E3 ubiquitin transferase and EC 2.3.2.31, RBR-type E3 ubiquitin transferase.
The enzyme appears in viruses and cellular organisms
- 2.3.2.26
- ligases
- proteasome
- smads
-
polyubiquitination
-
ubiquitin-proteasome
- adaptor
- tumorigenesis
- lysosomal
- osteoblast
- pten
-
ubiquitin-dependent
- endosomal
-
itch
-
ubiquitin-mediated
-
morphogenetic
-
endocytosis
- factor-beta
- rhoa
-
osteogenic
- rsp5
-
deubiquitinating
- oncoproteins
-
angelman
-
cell-expressed
- tgf-beta
- papillomavirus
-
e6-associated
- runx2
-
tensin
-
deubiquitinase
-
e3-ubiquitin
-
escrt
- ebola
- ehrlichiae
-
liddle
-
4-like
-
ubiquitin-binding
- chaffeensis
-
monoubiquitination
-
virus-like
-
proteasome-mediated
-
amiloride-sensitive
-
k63-linked
-
ubiquitin-conjugating
-
autoubiquitination
- analysis
-
ubiquitin-activating
- synthesis
-
ubiquitin-ligase
-
ubiquitination-mediated
-
smad1/5
- medicine
-
receptor-regulated
Reaction Schemes
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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
nedd4, smurf1, smurf2, huwe1, nedd4l, nedd4-1, e6-ap, ube3c, trp120, trip12, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
AO090012000923
ETC-1
HECT domain E3 ubiquitin ligase
HECT-type E3 ligase
HECT-type ubiquitin E3 ligase
Herc4
HulA
Huwe1
Itch
Nedd4
Nedd4L
RSP5
Smurf2
TRIP12
Ube3C
UBR1
UBR5
WWP1
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [HECT-type E3 ubiquitin transferase]-L-cysteine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [HECT-type E3 ubiquitin transferase]-S-ubiquitinyl-L-cysteine
(1a)
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-
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[HECT-type E3 ubiquitin transferase]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine = [HECT-type E3 ubiquitin transferase]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
(1b)
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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
HECT ligases directly catalyse protein ubiquitination and non-covalently interact with ubiquitin. The ubiquitin bindung surface on the HECT might act to bind a ubiquitin moiety that is already conjugated to a protein substrate, thus promoting polyubiquitination. Mutation in the ubiquitin bindung surface strongly impairs free-chain fdormation and ubiquitination of all substrates tested
[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
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PATHWAY SOURCE
PATHWAYS
MetaCyc
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)
In the first step the enzyme transfers ubiquitin from the E2 ubiquitin-conjugating enzyme (EC 2.3.2.23) to a cysteine residue in its HECT domain (which is located in the C-terminal region), forming a thioester bond. In a subsequent step the enzyme transfers the ubiquitin to an acceptor protein, resulting in the formation of an isopeptide bond between the C-terminal glycine residue of ubiquitin and the epsilon-amino group of an L-lysine residue of the acceptor protein. cf. EC 2.3.2.27, RING-type E3 ubiquitin transferase and EC 2.3.2.31, RBR-type E3 ubiquitin transferase.
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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
S-(ubiquitin)n-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [adenomatous polyposis coli]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-(ubiquitin)n-[adenomatous polyposis coli]-L-lysine
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Substrates: adenomatous polyposis coli protein functions as a negative regulator of the Wnt signaling pathway
Products: isoform HECTD1 modifies adenomatous polyposis coli with Lys63 polyubiquitin
Products: isoform HECTD1 modifies adenomatous polyposis coli with Lys63 polyubiquitin
?
S-(ubiquitin)n-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [Dvl2]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-(ubiquitin)n-[Dvl2]-L-lysine
Substrates: Dvl2 i.e. dishevelled, a central mediator for both Wnt/beta-catenin and Wnt/planar cell polarity pathways
Products: isoform NEDD4L mediates polyubiquitination of Dvl2 at Lys6, Lys27, and Lys29
Products: isoform NEDD4L mediates polyubiquitination of Dvl2 at Lys6, Lys27, and Lys29
?
S-(ubiquitin)n-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [Glis3]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-(ubiquitin)n-[Glis3]-L-lysine
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Substrates: Glis i.e. transcription factor Gli-similar 3
Products: isoform Itch significantly contributes to Glis3 polyubiquitination and reduces Glis3 stability by enhancing its proteasomal degradation. Itch-mediated degradation of Glis3 requires the PPxY motif-dependent interaction between Glis3 and the WW-domains of Itch as well as the presence of the Glis3 zinc finger domains. Itch dramatically inhibits Glis3-mediated transactivation and endogenous Ins2 expression by increasing Glis3 protein turnover
Products: isoform Itch significantly contributes to Glis3 polyubiquitination and reduces Glis3 stability by enhancing its proteasomal degradation. Itch-mediated degradation of Glis3 requires the PPxY motif-dependent interaction between Glis3 and the WW-domains of Itch as well as the presence of the Glis3 zinc finger domains. Itch dramatically inhibits Glis3-mediated transactivation and endogenous Ins2 expression by increasing Glis3 protein turnover
?
S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [caspase-8]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[caspase-8]-L-lysine
Substrates: -
Products: isoform HECTD3 ubiquitinates caspase-8 with K63-linked polyubiquitin chains that do not target caspase-8 for degradation but decrease the caspase-8 activation
Products: isoform HECTD3 ubiquitinates caspase-8 with K63-linked polyubiquitin chains that do not target caspase-8 for degradation but decrease the caspase-8 activation
?
S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [ING2]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[ING2]-L-lysine
Substrates: ING2 i.e. candidate tumor suppressor Inhibitor of Growth 2
Products: isoform Smurf1 interacts with and targets ING2 for poly-ubiquitination and proteasomal degradation. The ING2 binding domain in Smurf1 was mapped to the catalytic HECT domain. The C-terminal PHD domain of ING2 is required for Smurf1-mediated degradation
Products: isoform Smurf1 interacts with and targets ING2 for poly-ubiquitination and proteasomal degradation. The ING2 binding domain in Smurf1 was mapped to the catalytic HECT domain. The C-terminal PHD domain of ING2 is required for Smurf1-mediated degradation
?
S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [Sav]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[Sav]-L-lysine
S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [Spry2]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[Spry2]-L-lysine
Substrates: Spry2 is a regulator of receptor tyrosine kinase signaling in development and disease
Products: isoform Nedd4 polyubiquitinates Spry2 via Lys48 on ubiquitin and decreases its stability. The Spry2/Nedd4 association involves theWW domains of Nedd4 and requires phosphorylation of the Mnk2 kinase sites, Ser112 and Ser121, on Spry2. The phospho-Ser112/121 region on Spry2 that binds WW domains of Nedd4 is a non-canonical WW domain binding region that does not contain Pro residues after phospho-Ser
Products: isoform Nedd4 polyubiquitinates Spry2 via Lys48 on ubiquitin and decreases its stability. The Spry2/Nedd4 association involves theWW domains of Nedd4 and requires phosphorylation of the Mnk2 kinase sites, Ser112 and Ser121, on Spry2. The phospho-Ser112/121 region on Spry2 that binds WW domains of Nedd4 is a non-canonical WW domain binding region that does not contain Pro residues after phospho-Ser
?
S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [ubiquitin]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[ubiquitin]-L-lysine
Substrates: -
Products: isoform NleL functionally and structurally mimics eukaryotic HECT E3 ligases and catalyzes formation of unanchored polyubiquitin chains using Lys6 and Lys48 linkage. The catalytic cysteine residue forms a thioester intermediate with ubiquitin
Products: isoform NleL functionally and structurally mimics eukaryotic HECT E3 ligases and catalyzes formation of unanchored polyubiquitin chains using Lys6 and Lys48 linkage. The catalytic cysteine residue forms a thioester intermediate with ubiquitin
?
S-ubiquitinyl-[HECT-type E3 ubiquitin transferase]-L-cysteine + [Sox6 protein]-L-lysine
[HECT-type E3 ubiquitin transferase]-L-cysteine + N6-ubiquitinyl-[Sox6 protein]-L-lysine
S-ubiquitinyl-[Ubc-18]-L-cysteine + [IFY-1]-L-lysine
[Ubc-18]-L-cysteine + N6-ubiquitinyl-[IFY-1]-L-lysine
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Substrates: IFY-1 i.e. anaphase inhibitor securin
Products: -
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?
S-ubiquitinyl-[UbcH5a]-L-cysteine + [ubiquitin mutant G76V]-L-lysine
[UbcH5a]-L-cysteine + N6-ubiquitinyl-[mutant G76V]-L-lysine
Substrates: -
Products: -
Products: -
?
S-ubiquitinyl-[UbcH5a]-L-cysteine + [ubiquitin-DELTAGG]-L-lysine
[UbcH5a]-L-cysteine + N6-ubiquitinyl-[ubiquitin-DELTAGG]-L-lysine
Substrates: ubiquitin-DELTAGG i.e. mutant ubiquitin lacking the two C-terminal glycine residues, cannot be conjugated to other proteins
Products: -
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?
S-ubiquitinyl-[UbcH7]-L-cysteine + [endophilin A]-L-lysine
[UbcH7]-L-cysteine + N6-ubiquitinyl-[endophilin A]-L-lysine
Substrates: -
Products: isoform Itch ubiquitinates SH3 domain-containing protein endophilin A1 and the SH3/proline-rich domain interaction facilitates this activity. EGF treatment of cells stimulates endophilin A1 ubiquitination
Products: isoform Itch ubiquitinates SH3 domain-containing protein endophilin A1 and the SH3/proline-rich domain interaction facilitates this activity. EGF treatment of cells stimulates endophilin A1 ubiquitination
?
[AIP2-ubiquitin-conjugating enzyme E2]-S-ubiquitin-L-cysteine + [EGR2]-L-lysine
[AIP2-ubiquitin-conjugating enzyme E2]-L-cysteine + [EGR2]-N6-ubiquitinyl-L-lysine
Substrates: EGR2, a zinc finger transcription factor that has been found to regulate Fas ligand expression during activation-induced T-cell death
Products: -
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?
[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [CreD]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + [CreD]-N6-ubiquitinyl-L-lysine
[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [Dvl2]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + [Dvl2]-N6-ubiquitinyl-L-lysine
Substrates: -
Products: -
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?
[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [MalP]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + [MalP]-N6-ubiquitinyl-L-lysine
[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [MIZ1]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor MIZ1]-N6-ubiquitinyl-L-lysine
Substrates: acceptor protein i.e. MYC-interacting zinc-finger protein 1
Products: -
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?
[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [my-opioid receptor MOR1]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + [my-opioid receptor MOR1]-N6-ubiquitinyl-L-lysine
Substrates: -
Products: -
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?
[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [PEPCK1 protein]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + [PEPCK1 protein]-N6-ubiquitinyl-L-lysine
Substrates: -
Products: -
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?
[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [RAC1]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + [RAC1]-N6-ubiquitinyl-L-lysine
Substrates: RAC1 predominantly interacts with the middle domain of wild-type
Products: -
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?
[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [Spo12]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + [Spo12]-N6-ubiquitinyl-L-lysine
Substrates: -
Products: -
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?
[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [Ubl4A]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + [Ubl4A]-N6-ubiquitinyl-L-lysine
Substrates: Ubl4A, i.e. subunit of the Bag6 chaperone holdase complex. HUWE1 degrades unassembled Ubl4A in the cytoplasm
Products: -
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?
[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [WBP2]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + [WBP2]-N6-ubiquitinyl-L-lysine
Substrates: -
Products: -
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?
[HECT-E3-ubiquitin-carrier protein Arel1]-S-ubiquitin-L-cysteine + [SMAC]-L-lysine
[HECT-E3-ubiquitin-carrier protein Arel1]-L-cysteine + [SMAC]-N6-ubiquinyl-L-lysine
Substrates: SMAC i.e. proapoptotic protein second mitochondria-derived activator of caspase
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?
[HECT-E3-ubiquitin-carrier protein NEDD4L]-S-ubiquitin-L-cysteine + [Ubc5B]-L-lysine
[HECT-E3-ubiquitin-carrier protein NEDD4]-L-cysteine + [Ubc5B]-N6-ubiquinyl-L-lysine
-
Substrates: -
Products: -
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?
[HECT-E3-ubiquitin-carrier protein NEDD4]-S-ubiquitin-L-cysteine + [gamma-epithel Na+-channel]-L-lysine
[HECT-E3-ubiquitin-carrier protein NEDD4]-L-cysteine + [gamma-epithel Na+-channel]-N6-ubiquinyl-L-lysine
Substrates: His-tagged Ube2D3, in addition the reaction mixture contains purified E1 enzyme and ubiquitin
Products: -
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?
[HECT-E3-ubiquitin-carrier protein NEDD4]-S-ubiquitin-L-cysteine + [SQSTM1]-L-lysine
[HECT-E3-ubiquitin-carrier protein NEDD4]-L-cysteine + [SQSTM1]-N6-ubiquinyl-L-lysine
Substrates: SQSTM1 i.e. an autophagic cargo receptor involved in selective autophagy
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?
[Nedd4-1-ubiquitin-conjugating enzyme E2]-S-ubiquitin-L-cysteine + [activated Cdc42-associated tyrosine kinase]-L-lysine
[Nedd4-1ubiquitin-conjugating enzyme E2]-L-cysteine + [activated Cdc42-associated tyrosine kinase]-N6-ubiquitinyl-L-lysine
Substrates: activated Cdc42-associated tyrosine kinase is ubiquitinated by HECT E3 ubiquitin ligase Nedd4-1 and degraded along with epidermal growth factor receptor in response to epidermal growth factor stimulation. Activated Cdc42-associated tyrosine kinase interacts with Nedd4-1 through a conserved PPXY WW-binding motif. The WW3 domain in Nedd4-1 is critical for binding to activated Cdc42-associated tyrosine kinase. Deletion of the sterile alpha motif SAM-domain at the N-terminus dramatically reduces the ubiquitination of activated Cdc42-associated tyrosine kinase by Nedd4-1, while deletion of the Uba domain dramatically enhances the ubiquitination. Activated Cdc42-associated tyrosine kinase degradation is processed by lysosomes, not proteasomes
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?
[Nedd4-1-ubiquitin-conjugating enzyme E2]-S-ubiquitin-L-cysteine + [epidermal growth factor receptor]-L-lysine
[Nedd4-1-ubiquitin-conjugating enzyme E2]-L-cysteine + [epidermal growth factor receptor]-N6-ubiquitinyl-L-lysine
Substrates: epidermal growth factor receptor and activated Cdc42-associated tyrosine kinase are ubiquitinated by ubiquitin ligase Nedd4-1 in response to epidermal growth factor stimulation
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?
[Rsp-ubiquitin-conjugating enzyme UbcH5B]-S-ubiquitin-L-cysteine + [Sna3 cytoplasmic domain]-L-lysine
[Rsp5-ubiquitin-conjugating enzyme UbcH5B]-L-cysteine + [Sna3 cytoplasmic domain]-N6-ubiquitinyl-L-lysine
[TRIP1-ubiquitin-conjugating enzyme E2]-S-ubiquitin-L-cysteine + [APP-BP1]-L-lysine
[TRIP12-ubiquitin-conjugating enzyme E2]-L-cysteine + [APP-BP1]-N6-ubiquitinyl-L-lysine
Substrates: ubiquitin ligase TRIP12 functions as an E3 enzyme of APP-BP1 and additionally requires an E4 activity for polyubiquitination of APP-BP1. APP-BP1 is part of the ubiquitin-like protein NEDD8 activating enzyme. TRIP12 specifically interacts with the APP-BP1 monomer but not with the APP-BP1/Uba3 heterodimer. Overexpression of TRIP12 enhances the degradation of APP-BP1, whereas knockdown of TRIP12 stabilizes it
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[ubiquitin ligase HECTD3]-S-ubiquitin-L-cysteine + [Tara]-L-lysine
[ubiquitin ligase HECTD3]-L-cysteine + [Tara]-N6-ubiquitinyl-L-lysine
Substrates: Tara, Trio-associated repeat on actin, is an interacting partner of guanine nucleotide exchange factors Trio and TRF1. Ubiquitin-protein ligase HECTD3 directly binds Tara in vitro and forms a complex with Tara in vivo. Overexpression of HECTD3 enhances the ubiquitination of Tara in vivo and promotes the turnover of Tara, whereas depletion of HECTD3 by small interfering RNA decreases Tara degradation
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?
[ubiquitin-conjugating enzyme E2D3]-S-ubiquitin-L-cysteine + [latent membrane protein 2A LMP2A]-L-lysine
[ubiquitin-conjugating enzyme E2D3]-L-cysteine + [latent membrane protein 2A LMP2A]-N6-ubiquitinyl-L-lysine
Substrates: His-tagged Ube2D3, in addition the reaction mixture contains purified E1 enzyme and ubiquitin
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[ubiquitin-conjugating enzyme E2]-S-ubiquitin-L-cysteine + [transcription factor WRKY53]-L-lysine
[ubiquitin-conjugating enzyme E2D3]-L-cysteine + [transcription factor WRKY53]-N6-ubiquitinyl-L-lysine
Substrates: UPL5 is able to use the WRKY53 protein as a substrate for polyubiquitination in an in vitro system, and induction of UPL5 expression by an ethanol-inducible system in upl5 plants leads to degradation of the WRKY53 protein
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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
Substrates: -
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S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [Sav]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[Sav]-L-lysine
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Substrates: Sav i.e. scaffold protein Salvador, believed to promote Hpo/Wts association
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S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [Sav]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[Sav]-L-lysine
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Substrates: Sav i.e. scaffold protein Salvador, believed to promote Hpo/Wts association
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S-ubiquitinyl-[HECT-type E3 ubiquitin transferase]-L-cysteine + [Sox6 protein]-L-lysine
[HECT-type E3 ubiquitin transferase]-L-cysteine + N6-ubiquitinyl-[Sox6 protein]-L-lysine
Substrates: -
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S-ubiquitinyl-[HECT-type E3 ubiquitin transferase]-L-cysteine + [Sox6 protein]-L-lysine
[HECT-type E3 ubiquitin transferase]-L-cysteine + N6-ubiquitinyl-[Sox6 protein]-L-lysine
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Substrates: -
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[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [CreD]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + [CreD]-N6-ubiquitinyl-L-lysine
Substrates: CreD is ubiquitinated by HulA, and the ubiquitin modification state of CreD affects the glucose-induced endocytic degradation of the transporter MalP
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[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [CreD]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + [CreD]-N6-ubiquitinyl-L-lysine
Substrates: CreD is ubiquitinated by HulA, and the ubiquitin modification state of CreD affects the glucose-induced endocytic degradation of the transporter MalP
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[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [MalP]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + [MalP]-N6-ubiquitinyl-L-lysine
Substrates: HulA is responsible for the ubiquitin modification of MalP during glucose-induced MalP degradation, and the arrestin-like protein CreD is required for HulA targeting. Three (P/L)PxY motifs present in the CreD protein are essential for functioning as HulA adaptors. Four lysine residues of CreD are necessary for its ubiquitination
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[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [MalP]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + [MalP]-N6-ubiquitinyl-L-lysine
Substrates: HulA is responsible for the ubiquitin modification of MalP during glucose-induced MalP degradation, and the arrestin-like protein CreD is required for HulA targeting. Three (P/L)PxY motifs present in the CreD protein are essential for functioning as HulA adaptors. Four lysine residues of CreD are necessary for its ubiquitination
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[Rsp-ubiquitin-conjugating enzyme UbcH5B]-S-ubiquitin-L-cysteine + [Sna3 cytoplasmic domain]-L-lysine
[Rsp5-ubiquitin-conjugating enzyme UbcH5B]-L-cysteine + [Sna3 cytoplasmic domain]-N6-ubiquitinyl-L-lysine
Substrates: a specific HECT domain architecture may be important for ubiquitin ligation to Sna3 cytoplasmic domain, which involves both the catalytic C-lobe and the distal N-lobe packing differently from the arrangement promoting ubiquitin transfer from E2 enzyme to E3-ubiquitin intermediate
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[Rsp-ubiquitin-conjugating enzyme UbcH5B]-S-ubiquitin-L-cysteine + [Sna3 cytoplasmic domain]-L-lysine
[Rsp5-ubiquitin-conjugating enzyme UbcH5B]-L-cysteine + [Sna3 cytoplasmic domain]-N6-ubiquitinyl-L-lysine
Substrates: a specific HECT domain architecture may be important for ubiquitin ligation to Sna3 cytoplasmic domain, which involves both the catalytic C-lobe and the distal N-lobe packing differently from the arrangement promoting ubiquitin transfer from E2 enzyme to E3-ubiquitin intermediate
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additional information
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Substrates: isoform UPL5 interacts with transcription factor WRKY53 via its leucine zipper domain
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additional information
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Substrates: HECT ligases directly catalyse protein ubiquitination and non-covalently interact with ubiquitin. The ubiquitin bindung surface on the HECT might act to bind a ubiquitin moiety that is already conjugated to a protein substrate, thus promoting polyubiquitination. Mutation in the ubiquitin bindung surface (F707A and Y605A) mutants strongly impairs free-chain formation and ubiquitination of all substrates tested
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additional information
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Substrates: Nedd4 has a strong preference for building Lys63 ubiquitin-chains on substrates. Mutant F707A has defective chain elongation on substrate or shorter free chains
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additional information
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Substrates: high-risk human papilloma virus E6 oncoproteins interact with the ubiquitin ligase E6AP and target several cellular proteins, including p53 and proteins of the MAGI family, towards ubiquitin-mediated degradation. E6 oncoproteins from major high-risk human papilloma virus types 16, 18, 33 and 58 bind to a 15-mer peptide containing the LxxphiLsh motif of E6AP, where L indicates conserved leucine residues, phi is a hydrophobic residue, h is an amino acid residue with a side-chain capable of accepting hydrogen bonds, s represents a small amino acid residue and xx is a dipeptide where one of the residues is Asp, Asn, Glu or Gln. The equilibrium dissociation constants are in the low micromolar range. Low-risk human papilloma virus 11 E6 does not interact with E6AP. The two zinc-binding domains of E6 are required for E6AP recognition
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additional information
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Substrates: isoform E6-AP is loaded with ubiquitin by E2 enzyme UbcH5. A region of UbcH5 encompassing the catalytic site cysteine residue is critical for its ability to interact with E6-AP
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additional information
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Substrates: isoform E6-AP is loaded with ubiquitin by E2 enzyme UbcH5. A region of UbcH5 encompassing the catalytic site cysteine residue is critical for its ability to interact with E6-AP
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additional information
?
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Substrates: C2 domain of isoform Smurf1 functions in substrate selection
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additional information
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Substrates: UBE3B shows HECT E3 ubiquitin ligase activity and exhibits time-dependent auto-ubiquitylation activity
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additional information
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Substrates: UBE3B shows HECT E3 ubiquitin ligase activity and exhibits time-dependent auto-ubiquitylation activity
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additional information
?
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Substrates: UBE3C HECT domain assembles K48-linked polyubiquitin chains
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additional information
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Substrates: NEDD4 ubiquitination promotes a T-to-L conformational transition
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additional information
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Substrates: Lys903 in the HECT domain of the enzyme is the major site of autoubiquitination
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additional information
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Substrates: isoform Rsp5 is loaded with ubiquitin by E2 enzyme UbcH5. A region of UbcH5 encompassing the catalytic site cysteine residue is critical for its ability to interact with RSP5
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additional information
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Substrates: isoform Rsp5 is loaded with ubiquitin by E2 enzyme UbcH5. A region of UbcH5 encompassing the catalytic site cysteine residue is critical for its ability to interact with RSP5
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additional information
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Substrates: ubiquitin ligases HECT E3 use a two-step mechanism to ligate ubiquitin to target proteins. The second step of ligation is mediated by a distinct catalytic architecture established by both the HECT E3 and its covalently linked ubiquitin. There exist three-way interactions between ubiquitin and the bilobal HECT domain orienting the E3-ubiquitin thioester bond for ligation, and restricting the location of the substrate-binding domain to prioritize targets lysines for ubiquitination
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additional information
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Substrates: the type-1/2 substrate-binding sites of isoform UBR1, are located in the first 700 residues of the 1950-residue enzyme. Type-1 site is specific for basic N-terminal residues Arg, Lys, and His. The type-2 site is specific for bulky hydrophobic N-terminal residues Trp, Phe, Tyr, Leu, and Ile. Isoform UBR1 binds, with a Kd of about 1microM to either type-1 or type-2 N-terminal residues of reporter peptides but does not bind to a stabilizing N-terminal residue such as Gly
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additional information
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Substrates: UBR1 and CUP9, a transcriptional repressor of peptide import, interact nonspecifically and specific binding which involves, in particular, the binding by cognate dipeptides to theUBR1 type-1/2 substrate-binding sites, can be restored either by a chaperone such as EF1A or through macromolecular crowding
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additional information
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Substrates: isoform Rsp5 is loaded with ubiquitin by E2 enzyme UbcH5. A region of UbcH5 encompassing the catalytic site cysteine residue is critical for its ability to interact with RSP5
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?
additional information
?
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Substrates: ubiquitin ligases HECT E3 use a two-step mechanism to ligate ubiquitin to target proteins. The second step of ligation is mediated by a distinct catalytic architecture established by both the HECT E3 and its covalently linked ubiquitin. There exist three-way interactions between ubiquitin and the bilobal HECT domain orienting the E3-ubiquitin thioester bond for ligation, and restricting the location of the substrate-binding domain to prioritize targets lysines for ubiquitination
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additional information
?
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Substrates: the type-1/2 substrate-binding sites of isoform UBR1, are located in the first 700 residues of the 1950-residue enzyme. Type-1 site is specific for basic N-terminal residues Arg, Lys, and His. The type-2 site is specific for bulky hydrophobic N-terminal residues Trp, Phe, Tyr, Leu, and Ile. Isoform UBR1 binds, with a Kd of about 1microM to either type-1 or type-2 N-terminal residues of reporter peptides but does not bind to a stabilizing N-terminal residue such as Gly
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?
additional information
?
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Substrates: UBR1 and CUP9, a transcriptional repressor of peptide import, interact nonspecifically and specific binding which involves, in particular, the binding by cognate dipeptides to theUBR1 type-1/2 substrate-binding sites, can be restored either by a chaperone such as EF1A or through macromolecular crowding
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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
S-ubiquitinyl-[HECT-type E3 ubiquitin transferase]-L-cysteine + [Sox6 protein]-L-lysine
[HECT-type E3 ubiquitin transferase]-L-cysteine + N6-ubiquitinyl-[Sox6 protein]-L-lysine
S-ubiquitinyl-[HECT-type E3 ubiquitin transferase]-L-cysteine + [Sox6 protein]-L-lysine
[HECT-type E3 ubiquitin transferase]-L-cysteine + N6-ubiquitinyl-[Sox6 protein]-L-lysine
Substrates: -
Products: -
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?
S-ubiquitinyl-[HECT-type E3 ubiquitin transferase]-L-cysteine + [Sox6 protein]-L-lysine
[HECT-type E3 ubiquitin transferase]-L-cysteine + N6-ubiquitinyl-[Sox6 protein]-L-lysine
-
Substrates: -
Products: -
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?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4-[[(3-chloro-1,4-dioxo-1,4-dihydronaphthalen-2-yl)amino]methyl]-N-(pyridin-4-yl)benzamide
compound exhibits remarkable anticancer activity with tumor growth inhibition values of 98.3% and 100% at 25 mg/kg and 50 mg/kg orally daily, respectively, against human RPMI-8226 multiple myeloma xenograft. Treatment with the compound also shows a decrease of Itch level in human RPMI-8226 multiple myeloma cells
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Calmodulin
UBE3B interacts with calmodulin via its N-terminal isoleucine-glutamine motif. Deletion of the motif (amino acids 29-58) results in loss of calmodulin binding and a significant increase in the in vitro ubiquitylation activity of UBE3B. Changes in calcium levels in vitro disrupt the calmodulin-UBE3B interaction
clomipramine
antidepressant drug, specifically blocks isoform ITCH auto-ubiquitylation, as well as p73 ubiquitylation. Treating a panel of breast, prostate and bladder cancer cell lines with clomipramine, or its homologs, leads to reduced cancer cell growth, and synergize with gemcitabine or mitomycin in killing cancer cells by blocking autophagy. Minimum inhibitory concentration is 0.3 mM
ethyl 4-[(5,6-dichloro-1H-imidazo[4,5-b]pyrazin-2-yl)sulfanyl]butanoate
molecular docking suggests the imidazo[4,5-b]pyrazine scaffold undertakes a pi-stacking interaction with the phenolic group of tyrosine, and the ethyl ester enables strong ion-dipole interactions; molecular docking suggests the imidazo[4,5-b]pyrazine scaffold undertakes a pi-stacking interaction with the phenolic group of tyrosine, and the ethyl ester enables strong ion-dipole interactions
ethyl [(5,6-dichloro-1H-imidazo[4,5-b]pyrazin-2-yl)sulfanyl]acetate
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N-acetylphenylalanylamide
-
i.e. Phe-823 mimic, acts as a noncompetitive inhibitor of polyubiquitin chain elongation by destabilizing the active trimer
ubiquitinpropargylamine
activity-based probe, displays selectivity among HECT domains. Reactivity requires coordination of the C-tail of HUWE1 in the L-conformation
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[(5,6-dichloro-1H-imidazo[4,5-b]pyrazin-2-yl)sulfanyl]acetonitrile
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[1-[4-(trifluoromethyl)benzene-1-sulfonyl]-1H-indol-3-yl]methanol
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indole-3-carbinol
WWP1 inhibitor, treatment leads to down-regulation of the expressions of potential granulocyte markers SOX11 and AATase in haemocytes
additional information
autoinhibition mechanism of domains C2-HECT is not observed in isoform Smurf1
-
additional information
not inhibitory: NEDD4-inhibitor 1-benzylindole-3-carbinol; not inhibitory: NEDD4-inhibitor 1-benzylindole-3-carbinol
-
additional information
not inhibitory: NEDD4-inhibitor 1-benzylindole-3-carbinol; not inhibitory: NEDD4-inhibitor 1-benzylindole-3-carbinol
-
additional information
in the dimeric arrangement, HACE1 ubiquitination activity is hampered, the N-terminal helix of one monomer restricts access to the C-terminal domain of the other. The N-terminal 21 residues mediate autoinhibitory dimerization, and disruption of dimerization relieves the restriction on HACE1 activity
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ARRDC1
alpha-arrestin, anchoring an ARRDC1-GFP construct to the membrane results in efficient activation and autoubiquitination of NEDD4 ligase
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Ca2+
when the concentration of calcium is increased, calmodulin is released from UBE3B, resulting in an increase in ubiquitylation activity
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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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
0.1112
3,3'-diindolylmethane
Homo sapiens
autoubiquitination assay, pH 8, temperature not specified in the publication
0.1583
ethyl [(5,6-dichloro-1H-imidazo[4,5-b]pyrazin-2-yl)sulfanyl]acetate
Homo sapiens
autoubiquitination assay, pH 8, temperature not specified in the publication
1.011
indole-3-carbinol
Homo sapiens
autoubiquitination assay, pH 8, temperature not specified in the publication
0.2183
1-tosylindole-3-carbinol
Homo sapiens
autoubiquitination assay, pH 8, temperature not specified in the publication
0.2237
1-tosylindole-3-carbinol
Homo sapiens
autoubiquitination assay, pH 8, temperature not specified in the publication
0.03274
ethyl 4-[(5,6-dichloro-1H-imidazo[4,5-b]pyrazin-2-yl)sulfanyl]butanoate
Homo sapiens
autoubiquitination assay, pH 8, temperature not specified in the publication
0.2692
ethyl 4-[(5,6-dichloro-1H-imidazo[4,5-b]pyrazin-2-yl)sulfanyl]butanoate
Homo sapiens
autoubiquitination assay, pH 8, temperature not specified in the publication
0.09729
[(5,6-dichloro-1H-imidazo[4,5-b]pyrazin-2-yl)sulfanyl]acetonitrile
Homo sapiens
autoubiquitination assay, pH 8, temperature not specified in the publication
0.8563
[(5,6-dichloro-1H-imidazo[4,5-b]pyrazin-2-yl)sulfanyl]acetonitrile
Homo sapiens
autoubiquitination assay, pH 8, temperature not specified in the publication
0.6422
[1-[4-(trifluoromethyl)benzene-1-sulfonyl]-1H-indol-3-yl]methanol
Homo sapiens
autoubiquitination assay, pH 8, temperature not specified in the publication
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
isoform Itch co-localizes with markers of the endosomal system in a C2 domain-dependent manner and upon EGF stimulation, substrate endophilin A1 translocates to an EGF-positive endosomal compartment where it colocalizes with itch
brenda
the isoform Smurf1 C2 domain exerts a key role in localization to the plasma membrane. Lysine residues, Lys-28 and Lys-85, within the C2 domain are important for Smurf1 localization at the plasma membrane
brenda
shuttle of HECTD1 between cytoplasm and nucleus is mediated by exportin 1
brenda
HECTD1 contains putaxadtive nuclear localization and export signals. shuttle of HECTD1 between cytoplasm and nucleus is mediated by exportin 1
brenda
enzyme UBR5 localizes in the nuclei of smooth muscle cells and forms a complex with myocardin in vivo and in vitro
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
malfunction
physiological function
additional information
malfunction
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enzyme knockdown inhibits thioredoxin-interacting protein degradation and results in a subsequent increase in cardiomyocyte apoptosis
malfunction
-
enzyme knockdown inhibits thioredoxin-interacting protein degradation and results in a subsequent increase in cardiomyocyte apoptosis
malfunction
-
enzyme knockdown in C2C12 myotubes results in a concurrent increase in Sox6 protein levels and a decrease of Myh7 transcription
malfunction
natural mutation I827K is associated with the neurodevelopmental disorder of Angelman syndrome. The substitution destabilizes the 3D fold causing protein aggregation of the C-terminal lobe of E6AP. Mutant protein leads to decreased ubiquitin thiolester formation and ubiquitin discharge
malfunction
dysregulated enzyme functions like an oncoprotein to promote cancer growth and metastasis
physiological function
NEDD4-like ubiquitin protein ligase NEDL1 cooperates with p53 to induce apoptosis. During cisplatin -mediated apoptosis in neuroblastoma SH-SY5Y cells, p53 is induced to accumulate in association with an increase in expression levels of NEDL1. Enforced expression of NEDL1 results in a decrease in number of G418-resistant colonies in SH-SY5Y and U2OS cells bearing wild-type p53, whereas NEDL1 had undetectable effect on p53-deficient H1299 and SAOS-2 cells. Enforced expression of NEDL1 increases the number of U2OS cells with sub-G1 DNA content. NEDL1 binds to the COOH-terminal region of p53 and has an ability to enhance the transcriptional activity of p53. Small interfering RNA-mediated knockdown of the endogenous NEDL1 confers the resistance of U2OS cells to adriamycin. NEDL1 enhances pro-apoptotic activity of p53 in its catalytic activity-independent manner
physiological function
isoform UPL5 T-DNA insertion lines show the same senescence phenotype as transcription factor WRKY53 over-expressers. Over-expression of WRKY53 in the upl5 background enhances the accelerated senescence phenotype of WRKY53 over-expressers
physiological function
depletion of ubiquitin-protein ligase HECTD3 leads to multipolar spindle formation
physiological function
ubiquitin ligase UBR5 specifically enhances trans-activation of smooth muscle-specific promoters by the myocardin family of proteins. UBR5 significantly augments the ability of myocardin to induce expression of endogenous smooth muscle cell marker genes independent on its E3 ligase function. Depletion of endogenous UBR5 by small interfering RNA in fibroblast cells attenuates myocardin-induced smooth muscle-specific gene expression, and UBR5 knockdown in smooth muscle cells results in down-regulation of smooth muscle-specific genes. UBR5 can attenuate myocardin protein degradation resulting in increased myocardin protein expression without affecting myocardin mRNA expression. The effects of UBR5 on myocardin requires only the HECT and UBR1 domains of UBR5
physiological function
E3 ligase AIP2 positively regulates T-cell activation. Ectopic expression of AIP2 in mouse primary T cells enhances their proliferation and interleukin-2 production by suppressing the apoptosis of T cells. AIP2 interacts with and promotes ubiquitin-mediated degradation of EGR2, a zinc finger transcription factor that has been found to regulate Fas ligand expression during activation-induced T-cell death. Suppression of AIP2 expression by small RNA interference upregulates EGR2, inhibits EGR2 ubiquitination and Fas ligand expression, and enhances the apoptosis of T cells
physiological function
RNA interference knockdown of ubiqitin ligase Nedd4-1 inhibits degradation of both epidermal grwoth factor receptor and activated Cdc42-associated tyrosine kinase, and overexpression of activated Cdc42-associated tyrosine kinase mutants that are deficient in either binding to or ubiquitination by Nedd4-1 blocks epidermal growth factor-induced degradation of epidermal growth factor receptor
physiological function
silencing of endogenous isoform Nedd4 increases the cellular substrate Spry2 content and attenuates fibroblast growth factor-elicited ERK1/2. Mnk2 kinase silencing decreases Spry2-Nedd4 interactions and also augments the ability of Spry2 to inhibit fibroblast growth factor signaling
physiological function
-
isoform HectD1 promotes the adenomatous polyposis coli-axin interaction to negatively regulate Wnt signaling. Knockdown of HectD1 diminishes adenomatous polyposis coli ubiquitylation, disrupts the adenomatous polyposis coli-axin interaction, and augments Wnt3a-induced beta-catenin stabilization and signaling
physiological function
isoform NEDD4L induces Dvl2 polyubiquitination and targets Dvl2 for proteasomal degradation, thereby regulating the cellular beta-catenin level and Rac1, RhoA, and JNK activities
physiological function
-
ubiquitin ligase Smurf2 is required for the spindle checkpoint. Smurf2 localizes to the centrosome, mitotic midbody, and centromeres. Smurf2 depletion or the expression of a catalytically inactive Smurf2 results in misaligned and lagging chromosomes, premature anaphase onset, and defective cytokinesis. Smurf2 inactivation prevents nocodazole-treated cells from accumulating cyclin B and securin and prometaphase arrest. The silencing of Cdc20 in Smurf2-depleted cells restores mitotic accumulation of cyclin B and securin. Smurf2 depletion results in enhanced polyubiquitination and degradation of Mad2, a critical checkpoint effector. Mad2 is mislocalized in Smurf2-depleted cells
physiological function
T-DNA disruptions of the UPL3 locus do not affect overall growth and morphology, but display aberrant trichome morphology. Many mutant trichomes contain five or more branches instead of three branches. Mutant trichoimes often undergo an additional round of endoreplication resulting in enlarged nuclei with ploidy levels of up to 64C. Mutant plants are hypersensitive to gibberellic acid-3. The phenotype of upl3 mutants is similar to that of kaktus, a set of trichome mutants with supernumerary branches. UPL3 mutants and kaktus-2 are allelic with kaktus-2 plants harboring a splice-site mutation within the UPL3-transcribed region
physiological function
-
isoform Herc4 expression promotes scaffold protein Sav ubiquitylation and degradation, while Herc4 depletion stabilises Sav. Sav-binding protein Hpo reduces Sav/Herc4 interaction in a kinase-dependent manner
physiological function
-
deletion of isoform Rsp5 or mutation of its ligase activity, blocks the nuclear export of mRNAs. Affected messenger RNAs include both total poly(A)+ mRNA and heat-shock mRNAs. Mutation of Rsp5 does not affect nuclear protein import or export. Deletion of RSP5 blocks mRNA export, even under conditions where its essential role in unsaturated fatty acids biosynthesis is bypassed. The ligase activity is required for proper mRNA export
physiological function
HECTD3 depletion can sensitize cancer cells to extrinsic apoptotic stimuli. HECTD3 inhibits TNF-related apoptosis-inducing ligand-induced caspase-8 cleavage in an E3 ligase activity-dependent manner. Mutation of the caspase-8 ubiquitination site at K215 abolishes the HECTD3 protection from TNF-related apoptosis-inducing ligand-induced cleavage
physiological function
-
HECT-E3 ligase ETC-1 is a regulator of the cytoplasmic anaphase inhibitor securin IFY-1 level. RNAi-mediated depletion of ETC-1 stabilizes IFY-1 and cyclin B1 in post-meiosis I embryos. ETC-1 knockdown in a reduced anaphase promoting complex/cyclosome function background causes an embryonic lethal phenotype. In vitro, ETC-1 ubiquitylates IFY-1 and CYB-1 in the presence of the E2 enzyme UBC-18, which functions in pharyngeal development. UBC-18 plays a distinct role together with ETC-1 in regulating the cytoplasmic level of IFY-1 during meiosis
physiological function
in a temperature-sensitive mutant strain of isoform Rsp5, ubiquitin is limiting. Reduced synthesis of ubiquitin appears to contribute to ubiquitin depletion. In a wildtype strain upon heat-shock, transient inhibition of general protein synthesis is observed. Wildtype cells quickly recover from this transient arrest, the Rsp5 mutant cells remain arrested
physiological function
isoform TRIP12 catalyzes in vitro ubiquitination of ubiquitin fusion degradation substrates in conjunction with E1, E2, and E4 enzymes. Knockdown of TRIP12 stabilizes artificial ubiquitin fusion degradation substrates and physiological substrate, mutant ubiquitin UBB+1. TRIP12 knockdown reduces UBB+1-induced cell death in human neuroblastoma cells. Complementation of TRIP12 knockdown cells with the TRIP12 HECT domain mostly restores efficient degradation of ubiquitin fusion degradation substrates. The TRIP12 HECT domain directs ubiquitination of ubiquitin fusion degradation substrates in vitro and can be specifically cross-linked to the ubiquitin moiety of the substrates in vivo. A mutant ubiquitin that cannot be conjugated to other proteins is a substrate of the TRIP12 HECT domain both in vivo and in vitro
physiological function
-
the enzyme targets thioredoxin-interacting protein for ubiquitin-proteasome degradation in cardiomyocytes and ameliorates reactive oxygen species-induced cardiotoxicity through the thioredoxin system. The enzyme protects cardiac remodeling, cardiac function, and survival rate in myocardial infarction
physiological function
-
the enzyme targets thioredoxin-interacting protein for ubiquitin-proteasome degradation in cardiomyocytes and ameliorates reactive oxygen species-induced cardiotoxicity through the thioredoxin system. The enzyme protects cardiac remodeling, cardiac function, and survival rate in myocardial infarction
physiological function
the enzyme targets transcription factor Sox6 for proteasomal degradation and affects fiber type-specific gene expression in muscle cells
physiological function
-
the enzyme targets transcription factor Sox6 for proteasomal degradation and affects fiber type-specific gene expression in muscle cells
physiological function
the Huwe1 HECT domain prioritizes K6- and K48-polyubiquitin chains and does not interact with ubiquitin in a non-covalent manner. The architecture of the C-lobe-ubiquitin intermediate is conserved between Huwe1 and Smurf2 and involves a reorientation of the very C-terminal residues. The individual sequence composition of the Huwe1 C-terminal tail modulates ubiquitination activity, without affecting thioester formation
physiological function
HECT E3 ligase adopts an autoinhibited state, in which its multiple WW domains sequester HECT using a multi-lock mechanism. Removing WW2 or WW34 leads to a partial activation of WWP1. The multi-lock regulation mechanism is conserved in WWP2 and Itch, whereas in Nedd4/4 L and Smurf2, a variant version of the multi-lock autoinhibition mode is utilized
physiological function
mutating the catalytic cysteine or deleting the entire HECT domain (amino acids 758-1068) results in loss of UBE3B's ubiquitylation activity. Knockdown of UBE3B in human cells induces changes in mitochondrial morphology and physiology, a decrease in mitochondrial volume, and a severe suppression of cellular proliferation
physiological function
loss of Ubr-5 function suppresses defects caused by reduced signaling via Notch-type receptors GLP-1 or LIN-12. Ubr-5 mutations do not suppress embryonic or larval lethality associated with mutations in downstream transcription factor, LAG-1. In the gonad, Ubr-5 acts in the receiving cells (germ cells) to limit GLP-1 signaling activity. Ubr-5 acts redundantly with the F-box component of SCFSEL-10 E3 ubiquitin-ligase SEL-10 to limit Notch signaling in certain tissues
physiological function
Smurf2 mediates [D-Ala2,NMePhe4,Gly5-ol]-enkephalin (DAMGO, an agonist of MOR1)-induced MOR1 ubiquitination and degradation. DAMGO decreases MOR1 levels in the ubiquitin-proteasome system. MOR1 is modified by a Lys48-linked polyubiquitin chain. Overexpression of Smurf2 induces MOR1 ubiquitination and accelerates DAMGO-induced MOR1 degradation, whereas downregulation of Smurf2 attenuates MOR1 degradation. DAMGO increases lung epithelial cell migration and proliferation, and the effect is attenuated by overexpressing Smurf2
physiological function
NEDD4 ligase activation critically requires a substantial array of clustered PY motifs. Soluble protein substrates and adaptors such as alpha-arrestins, even with multiple PY elements, cannot activate ligase activity efficiently. Polymerization or membrane tethering of these substrates dramatically increases the ligase activity both in vivo and in vitro. Aggregation of luciferase-containing substrates upon heat shock has a similar effect and can also expose cryptic PY elements in the substrates
physiological function
inactivation of ubiquitin ligase HectPH1 is sufficient to reconstitute the parental phenotype of mutants defective in the TORC2 Pia subunit, which are impaired in chemotaxis and development. HectPH1 deletion rescues both chemotactic cell polarity and the underlying PKB phosphorylation and kinase activity of mutants defective in the TORC2 Pia subunit
physiological function
HUWE1 is a ubiquitin ligase for substrates bearing unshielded, hydrophobic segments. Many endogenous HUWE1 substrates form multi-protein complexes that function in the nucleus although HUWE1 itself is cytoplasmically localized. Inhibition of nuclear entry enhances HUWE1-mediated ubiquitination and degradation
physiological function
ubiquitin ligase Tom1 contributes to the turnover of Spo12, a component of the Cdc14 early anaphase release network, in G2/M phase. Tom1 and Spo12 interact. Overexpression of Spo12 is cytotoxic in the absence of Tom1. In S phase, Spo12 is degraded even in the absence of Tom1 and Cdh1
physiological function
-
monomeric NEDD4L catalyzes only HECT ubiquitin thioester formation and monoubiquitination, whereas polyubiquitin chain assembly requires NEDD4L oligomerization and sites 1 and 2 to function in trans
physiological function
-
Ehrlichia chaffeensis tandem repeat protein TRP120 is posttranslationally modified by ubiquitin. Ubiquitination occurs through intrinsic and host-mediated HECT ligase activity. The C-terminal region of TRP120 harbors a functional HECT E3 ligase domain with a conserved catalytic site. TRP120 autoubiquitination occurs in vitro in the presence of host UbcH5b/c E2 enzymes. Human HECT E3 ubiquitin ligase, Nedd4L, interacts with TRP120 during infection and also mediates TRP120 ubiquitination. Nedd4L knockdown results in the reduction of TRP120 ubiquitination, decreases ehrlichial infection, and reduces recruitment of TRP120-interacting host protein, PCGF5, to ehrlichial inclusions. TRP120-mediated PCGF5 polyubiquitination is associated with a reduction in PCGF5 levels. Inhibition of ubiquitination with small molecules also significantly decreases ehrlichial infection
physiological function
Ehrlichia chaffeensis tandem repeat protein TRP120 is posttranslationally modified by ubiquitin. Ubiquitination occurs through intrinsic and host-mediated HECT ligase activity. HECT E3 ubiquitin ligase, Nedd4L, interacts with TRP120 during infection and also mediates TRP120 ubiquitination. Nedd4L knockdown results in the reduction of TRP120 ubiquitination, decreases ehrlichial infection, and reduces recruitment of TRP120-interacting host protein, PCGF5, to ehrlichial inclusions. TRP120-mediated PCGF5 polyubiquitination is associated with a reduction in PCGF5 levels. Inhibition of ubiquitination with small molecules also significantly decreases ehrlichial infection
physiological function
mice lacking Nedd4 globally or only in the myeloid compartment are highly susceptible to systemic Candida albicans infection, and show heightened organ fungal burden, defective inflammatory response, impaired leukocyte recruitment to the kidneys, and defective reactive oxygen species expression by granulocytes. Nedd4-/- macrophages display impaired activation of TGF-beta-activating kinase-1 and NF-kappaB, but normal activation of spleen tyrosine kinase and protein kinase C-delta on C. albicans yeast and hyphal infections. Nedd4 positively regulates signaling through dectin-1 and dectin-2/3
physiological function
after high-fed conditioning, a loss-of-function mutant shows defects in high-salt migration as well as low-salt migration abnormality after low-fed conditioning, and defects in all kinds of starved conditioning
physiological function
after high-fed conditioning, a loss-of-function mutant shows defects in high-salt migration as well reduced migration after low-starved and middle-starved conditioning. The ubr-5/hecd-1 mutant and the wwp-1/hecd-1 mutants show an additive phenotype after low-starved conditioning
physiological function
after high-fed conditioning, a loss-of-function mutant shows defects in high-salt migration, and low-salt migration abnormality after low-fed conditioning. The wwp-1/hecd-1 mutant shows an additive phenotype, while wwp-1 and ubr-5 function in the same genetic pathway
physiological function
a loss-of-function mutant shows abnormal salt chemotaxis after low-starved conditioning. The ubr-5/hecd-1 mutant shows an additive phenotype. The ubr-5 mutation enhances low-salt migration bias in the hecd-1 mutant after middle/fed, high/fed and middle/starved conditioning. The wwp-1/ubr-5 mutant does not show significant difference compared to the wwp-1 single mutant
physiological function
a loss-of-function mutant shows abnormal salt chemotaxis after high-starved conditioning
physiological function
a loss-of-function mutant shows enhanced migration to high salt after low-starved and middle-starved conditioning
physiological function
HECTD1 depletion in HEK-93T and HeLa cells decreases cell number, mediated through loss of ubiquitin ligase activity. HECTD1 depletion increases the proportion of cells with aligned chromosomes. HECTD1-depleted cells take on average longer to go through mitosis. HECTD1 depletion reduces the activity of the Spindle Assembly Checkpoint. BUB3, a component of the Mitosis Checkpoint Complex, interacts with HECTD1
physiological function
HECTD1 interacts with transcription factor SNAIL and regulates its stability through ubiquitination. The knockdown of HECTD1 increases the expression levels of SNAIL. Treatment with leptomycin B results in the nuclear retention of HECTD1, associated with the loss of SNAIL expression. The knockdown of HECTD1 in HeLa cells increases cell migration and induces a mesenchymal phenotype
physiological function
mice with cardiac-specific overexpression of ITCH show attenuated cardiac hypertrophy after transverse aortic constriction, and the survival rate is higher for ITCH overexpressing mice than for wild-type. ITCH interacts with disheveled proteins (Dvls), and expression of key molecules of the Wnt/beta-catenin signaling pathway (Dvl1, Dvl2, GSK3beta and beta-catenin) is inhibited in overexpressing mice compared with wild-type. The ubiquitination level of Dvl proteins increases in overexpressing mice
physiological function
knockdown of ITCH increases cardiomyocyte size and augments protein expression levels of Dvl proteins, phospho-GSK3beta, and beta-catenin after Wnt3a stimulation. Overexpression of ITCH attenuates cardiomyocyte hypertrophy and decreases protein expression levels of Dvl proteins, phospho-GSK3beta and beta-catenin
physiological function
UBR5 acts as a regulator of MYC oncogenen degradation. UBR5 depletion leads to accumulation of MYC, even in presence of functional MYC ligase, FBXW7. UBR5 interacts with MYC. Upon loss of UBR5, reduced K48-linked ubiquitination of MYC is observed. In cancer cell lines with amplified MYC expression, depletion of UBR5 results in reduced cell survival
physiological function
the enzyme influences innate immunity, proteasome processivity, and cancer metastasis
physiological function
-
isoform Herc4 expression promotes scaffold protein Sav ubiquitylation and degradation, while Herc4 depletion stabilises Sav. Sav-binding protein Hpo reduces Sav/Herc4 interaction in a kinase-dependent manner
-
additional information
the HUWE1 HECT N-lobe noncovalently binds to Ub with both subdomains, forming a stable complex. Residues D4029, Y4031, R4032, P4076, M4077, Y4078, A4079, C4099, N4100, Y4106, F4181, and G4182 in the HECT N-lobe mainly contribute to the binding free energy
additional information
HECTD2 is involved in promoting melanoma cell-intrinsic proliferation and drug resistance and counteracting anti-tumour adaptive immunity and immunotherapy. HECTD2 expression directly promoted cell-autonomous proliferation of human melanoma cells in vitro and murine melanoma cells in vitro and in vivo
Show AA Sequence and Transmembrane Helices (70054 entries)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
113000
200000
42200
x * 42200, enzyme including an additional five-residue peptide (Gly-Pro-Leu-Gly-Ser), calculated from amino acid sequence
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
HACE1 is a homodimer, with monomers arranged in an antiparallel manner, cryo-EM data. In the dimeric arrangement, HACE1 ubiquitination activity is hampered, the N-terminal helix of one monomer restricts access to the C-terminal domain of the other
additional information
-
the predicted intersubunit interface has an absolutely conserved residue Phe823, substitution of which destabilizes the trimer and results in an over 10000fold decrease in kcat for polyubiquitin chain assembly
?
x * 42200, enzyme including an additional five-residue peptide (Gly-Pro-Leu-Gly-Ser), calculated from amino acid sequence
?
x * 99900, calculated from sequence, x * 126000, SDS-PAGE of recombinant protein including GST-tag
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ubiquitination
ubiquitination
-
TRP120 is posttranslationally modified by ubiquitin. Ubiquitination occurs through intrinsic and host-mediated HECT ligase activity
ubiquitination
residue Lys903 in the UBE3C HECT domain is a major site of autoubiquitination
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
structure of isoform NleL contains two domains, a beta-helix domain formed by pentapeptide repeats and a bilobed catalytic domain reminiscent of the N- and C-lobe architecture of HECT E3s. The C-lobe adopts a large range of different positions relative to the N-lobe, indicating that the helix linking the two lobes is extremely flexible
C2 domain, to 1.96 A resolution. The Smurf1 C2 domain possesses a typical anti-parallel beta-sandwich fold. The Smurf1 C2 domain exerts a key role in localization to the plasma membrane. Lysine residues, Lys-28 and Lys-85, within the C2 domain are important for Smurf1 localization at the plasma membrane, regulation on cell migration, and robust ligase activity toward RhoA, which further supports a Ca2+-independent localization mechanism for Smurf1
cryo-EM structures, HACE1 comprises of an N-terminal AKR domain, a middle domain, and a C-terminal HECT domain
crystal structure of the extended HECT domain of AREL1 (amino acids 436-823) at 2.4 A resolution. The extended HECT domain adopts an inverted, T-shaped, bilobed conformation and harbors an additional loop (aa 567-573) absent in other HECT members. The N-terminal extended region (aa 436-482) preceding the HECT domain is indispensable for its stability and activity and without this region, the HECT domain becomes inactive
crystal structure of the HECT domain of human ubiquitin ligase WWP1/AIP5 maintains a two-lobed structure like the HECT domain of the human ubiquitin ligase E6AP. The organization of the two lobes relative one another is different from E6AP due to a rotation about a polypeptide hinge linking the N and C lobes
crystal structure of the HECT domain of UBE3C (amino acids 744-1083) with an additional fifty N-terminal amino acids (aa 693-743) at 2.7 A. The UBE3C HECT domain forms an open, L-shaped, bilobed conformation, having a large N-lobe and a small C-lobe. The N-terminal region (aa 693-743) preceding the UBE3C HECT domain as well as a loop region (aa 758-762) in the N-lobe of the HECT domain affect the stability and activity of UBE3C HECT domain
hanging drop vapor diffusion method, using 0.1 M HEPES pH 8.4, 0.2 M MgCl2, 15% (v/v) ethanol at 4°C
Huwe1 C-lobe-ubiquitin crystal structure at 2.8 A resolution, by molecular replacement and solution NMR spectroscopy
Smurf2 C-lobe-ubiquitin crystal structure at 2.8 A resolution, by molecular replacement and solution NMR spectroscopy
structure of the C-terminal lobe of the catalytic domain of E6AP. Two molecules are found in a domain-swapped, dimeric arrangement. The molecular hinge alowing the structural reorganization coincides with the active-site region
structure of the C-terminal lobe of the catalytic domain. Two molecules are found in a domain-swapped, dimeric arrangement. The molecular hinge alowing the structural reorganization coincides with the active-site region
structure of ubiquitin-loaded human neural precursor cellexpressed developmentally downregulated protein, Nedd4, to 2.51 A resolution. The Nedd4-HECT domain-ubiquitin transitory intermediate provides a structural basis for the proposed sequential addition mechanism. The donor ubiquitin, transferred from the E2, is bound to the Nedd4 C lobe with its C-terminal tail locked in an extended conformation, primed for catalysis. Nedd4-family members are Lys63-specific enzymes whose catalysis is mediated by an essential C-terminal acidic residue
structures of Nedd4 HECT domain, alone (2.5 A) and in complex with ubiquitin (2.7 A), showing new binding modes involving two surfaces on ubiquitin and both subdomains of the HECT N-lobes, suggesting an model for the HECT-t-substrate ubiquitin transfer, in which the growing chain on the substrate is kept close to the catalytic cysteine to promote processivity HECTNedd4 displays the typical HECT fold, composed of two lobes connected by a flexible hinge. The N-lobe consists of two moieties, the large and the smal subdomains. The small domains host the E2-binding site and the large carries the catalytic cysteine
structures of ubiquitin variants in complex with the HECT domains of human E3 HECT ligases
-
structures of WWP1 in its fully inactive and partially active states. Domains WW2, L, and WW4 are organized into a headset architecture, in which the WW2 and WW4 domains are bound to bilateral sites within the N-lobe, and L forms a kinked alpha-helix that is tucked into the cleft between the N- and C-lobes of HECT
crystal structure of a trapped complex of ubiquitin ligase Rsp5 with ubiquitin and substrate Sna3 cytoplasmic domain as a proxy for the catalytic intermediate. The covalent linkage between ubiquitin and the HECT domain is oriented by ubiquitin interactions with the HECT domain N- and C-lobes that stabilize HECT domain conformation. The HECT domain architecture of the ligase primed for ligation prioritizes potential target lysines by their placement relative to a composite catalytic center for ubiquitination
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A2790W
the mutant shows strongly reduced activity compared to the wild type enzyme
C716A
-
mutation in catalytic cysteine. Cells transfected with C716A fail to accumulate securin with significant reduction in Mad2 level. Cell show a significant increase in cells displaying misaligned chromosomes, lagging chromosomes during mitotic exit, and multinucleation
C922A
-
dominant-negative active site mutant, predicted to result in an end point of 33% activity compared with wild-type. Addition of mutant C922A to the wild-type enzyme at saturating concentration inhibits wild-type NEDD4L to 30% limiting activity
D900A
mutant is defective in autoubiquitination. Mutation leads to the accumulation of the E3-Ub covalent intermediate, which is not transferred to a Lys side-chain amine
D900E
mutant is defective in autoubiquitination, D900E is the least impaired in the group. Mutation leads to the accumulation of the E3-Ub covalent intermediate, which is not transferred to a Lys side-chain amine
D900N
mutant is defective in autoubiquitination. Mutation leads to the accumulation of the E3-Ub covalent intermediate, which is not transferred to a Lys side-chain amine
DELTA21
deletion of N-terminal 21 amino acids, enhances activity as compared to wild-type
DELTA382-385
HECT domain mutant, capable of forming DTT-sensitive HECT-ubiquitin thioesters, defective in polyubiquitination
DELTA383-385
HECT domain mutant, capable of forming DTT-sensitive HECT-ubiquitin thioesters, defective in polyubiquitination
DELTA384-385
HECT domain mutant, capable of forming DTT-sensitive HECT-ubiquitin thioesters, defective in polyubiquitination
DELTAD897/D900E
mutant is impaired in autoubiquitination, but slightly more active than mutant D900E
DELTAD900
mutant is defective in autoubiquitination. Mutation leads to the accumulation of the E3-Ub covalent intermediate, which is not transferred to a Lys side-chain amine
E4054A
variant displays reduced autoubiquitination and ubiquitin chain formation activities
E4064A
variant displays reduced autoubiquitination and ubiquitin chain formation activities
E411Q/E415Q
about 6fold decrease of affinity to human papilloma virus E6 oncogens
E701A
substitution in the Arel1 HECT domain, substantially increases its autopolyubiquitination and SMAC ubiquitination activity
E748A
mutant produces thioester levels comparable to the wild-type and shows enhanced polyubiquitination activity
F2732A
the mutant shows strongly reduced activity compared to the wild type enzyme
F4181A
mutation in the N-lobe, almost completely abolishes the interaction with Ub
F707A
Nedd4 mutant, almost abolished HECTNedd4 binding to Lys 63 ubiquitin. Mutant F707A has defective chain elongation on substrate or shorter free chains
F823D
-
no detectable free or anchored polyubiquitin chain assembly is observed with the mutant
G383A/L384A
mutant produces thioester levels comparable to the wild-type
I827K
natural mutation associated with Angelman syndrome. The substitution destabilizes the 3D fold causing protein aggregation of the C-terminal lobe of E6AP
K1013Q
mutation increases the formation of E3-Ub thioester intermediate and shows 2fold enhanced ubiquitination activity
L224K
the mutant shows slightly reduced activity compared to the wild type enzyme
L346P
mutation abolishes E2-E3 transthiolation and consequently polyubiquitination activity
L384A
mutant produces thioester levels comparable to the wild-type
L4061A
variant displays reduced autoubiquitination and ubiquitin chain formation activities
L409V
about 30fold decrease of affinity to human papilloma virus E6 oncogens characterised by very fast dissociation rates
L413S
about 40fold decrease of affinity to human papilloma virus E6 oncogens characterised by very fast dissociation rates
medicine
N4102A
mutation in the N-lobe, interaction with Ub is similar to wild-type
Q961A
mutation of residues in the HECT domain, substantial decrease in autoubiquitination activity and in the formation of E3-Ub thioester intermediate
Q961E
mutation substantially reduces the formation of E3-Ub thioester intermediate
R332A
mutation in the middle domain, increases ubiquitination activity on substrate RAC1
Ser1049
mutation of residues in the HECT domain, substantial decrease in autoubiquitination activity
V140A
mutation in the AKR domain, enhances ubiquitination activity on substrate RAC1
V196K
the mutant shows slightly reduced activity compared to the wild type enzyme
V747A/E748A
mutant produces thioester levels comparable to the wild-type
Y2576A
the mutant shows reduced activity compared to the wild type enzyme
Y605A
Nedd4 mutant, almost abolished HECTNedd4 binding to Lys 63 ubiquitin
additional information
medicine
isoform HECTD3 is frequently overexpressed in breast carcinomas suggesting that caspase-8 ubiquitination by HECTD3 confers cancer cell survival
medicine
many WWP1 mutations identified in cancer patients result in a partially active state with increased E3 ligase activity, and the WWP1 mutants likely promote cell migration by enhancement of DELTANp63alpha degradation
additional information
deletion of the last three amino acids at the C-terminus of Arel1 completely abrogates Arel1 autoubiquitination and reduces SMAC ubiquitination
additional information
the deletion of the last three amino acids at the C-terminal completely abrogates UBE3C activity. Deletion of a loop of amino acids 758-762 decreases temperature stability and leads to lack of autoubiquitination but does not affect E2-E3 transthiolation process
additional information
semisynthetic NEDD4 proteins containing the unnatural stereoisomeric amino acids D-Asp or D-Glu or a sulfonate at position 900 show reduced Ub ligase activity. 4-fluoro-Phe896-NEDD4 is highly defective in autoubiquitination. 2-fluoro-Phe896 and 3-fluoro-Phe896 NEDD4 forms show comparable catalytic activity to mutant D955A
additional information
an NTR-deleted enzyme (D1-875) exhibits compromised but not abolished activity
additional information
the deletion of the last three amino acids at the at the C-terminal completely abrogates the enzyme activity while mutations of Gln961 and Ser1049 residues in the HECT domain substantially decrease its autoubiquitination activity
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme expression is increased 3 h after Dox stimulation (0.0005 mM)
inhibitor indole-3-carbinol also decrease the expression level by 0.8fold after 12h
Smurf2 protein levels increase significantly with advanced age in a region-specific manner but not globally in the zebrafish brain. Expression of interacting partners, Ep300a and Sirt1, correlates with Smurf2 expression
the enzyme is highly expressed in a substantial proportion of breast, ovarian, prostate, gastric, and pancreatic cancers
UPL5 is highly expressed in leaf tissue but expression is reduced at bolting when transcription factor WRKY53 protein levels should be high
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
medicine
synthesis
construcution of a soluble HECT domain truncation of isoform WWP2 which is amendable for preparation scale expression in Escherichia coli. A relatively simple purification process achieves highly pure protein by employing immobilized metal-affinity chromatography followed by salting out, ion exchange chromatography and finally, size exclusion chromatography. Procedure allows to obtain about 60 mg/L of the soluble protein
analysis
-
development of ubiquitin variants that inhibit or activate HECT E3 enzymes. Ubiquitin variant inhibitors block the E2-binding site, and activators occupy a ubiquitin-binding exosite. Ubiquitin variants reveal regulation mechanisms among NEDD4 subfamily HECTs and are useful for modulating therapeutically relevant targets of HECT E3s in cells and intestinal organoids. Ubiquitin variant activators bind to the N-lobe exosite and differentially modulate related HECT E3 ligases
analysis
-
application of ubiquitin-activity-based probes such as ubiquitin-vinyl methylester, ubiquitin-propargylamide to label HECT domains. E2-Ub-activity-based probes can label the catalytic HECT domains of NEDD4, UBE3C, and HECTD1
analysis
application of ubiquitin-activity-based probes such as ubiquitin-vinyl methylester, ubiquitin-propargylamide to label HECT domains. E2-Ub-activity-based probes can label the catalytic HECT domains of NEDD4, UBE3C, and HECTD1
medicine
functional interaction of NEDD4-like ubiquitin protein ligase NEDL1 with p53 might contribute to the induction of apoptosis in cancerous cells bearing wild-type p53
medicine
high-risk human papilloma virus E6 oncoproteins interact with the ubiquitin ligase E6AP and target several cellular proteins, including p53 and proteins of the MAGI family, towards ubiquitin-mediated degradation. E6 oncoproteins from major high-risk risk human papilloma virus types 16, 18, 33 and 58 bind to a 15-mer peptide containing the LxxphiLsh motif of E6AP, where L indicates conserved leucine residues, phi is a hydrophobic residue, h is an amino acid residue with a side-chain capable of accepting hydrogen bonds, s represents a small amino acid residue and xx is a dipeptide where one of the residues is Asp, Asn, Glu or Gln. The equilibrium dissociation constants are in the low micromolar range. Low-risk risk human papilloma virus 11 E6 does not interact with E6AP. The two zinc-binding domains of E6 are required for E6AP recognition
medicine
antidepressant drug clomipramine specifically blocks ITCH auto-ubiquitylation, as well as p73 ubiquitylation. Treating a panel of breast, prostate and bladder cancer cell lines with clomipramine, or its homologs, leads to reduced cancer cell growth, and synergize with gemcitabine or mitomycin in killing cancer cells by blocking autophagy
medicine
in cervical cancer specimens, the decreased expression levels of HECTD1 are significantly associated with a poor patient survival
medicine
in cancer cell lines with amplified MYC oncogene expression, depletion of UBR5 results in reduced cell survival. MYC and UBR5 are coamplified in more than 40% of cancer cells and MYC copy number amplification correlates with enhanced transcriptional output of UBR5
medicine
HECTD2 cell autonomously drives the proliferation of human and murine melanoma cells by accelerating the cell cycle. HECTD2 additionally regulates cancer cell production of immune mediators. Higher HECTD2 expression is associated with weaker anti-tumour immunity and unfavourable outcome of PD-1 blockade in human melanoma and counteracts immunity against a model tumour antigen in murine melanoma
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Nuber, U.; Scheffner, M.
Identification of determinants in E2 ubiquitin-conjugating enzymes required for hect E3 ubiquitin-protein ligase interaction
J. Biol. Chem.
274
7576-7582
1999
Saccharomyces cerevisiae (P39940), Saccharomyces cerevisiae, Homo sapiens (Q05086), Homo sapiens, Saccharomyces cerevisiae ATCC 204508 (P39940)
brenda
Yu, J.; Lan, J.; Zhu, Y.; Li, X.; Lai, X.; Xue, Y.; Jin, C.; Huang, H.
The E3 ubiquitin ligase HECTD3 regulates ubiquitination and degradation of Tara
Biochem. Biophys. Res. Commun.
367
805-812
2008
Homo sapiens (Q5T447)
brenda
Park, Y.; Yoon, S.K.; Yoon, J.B.
TRIP12 functions as an E3 ubiquitin ligase of APP-BP1
Biochem. Biophys. Res. Commun.
374
294-298
2008
Homo sapiens (Q14669)
brenda
Xia, Z.; Webster, A.; Du, F.; Piatkov, K.; Ghislain, M.; Varshavsky, A.
Substrate-binding sites of UBR1, the ubiquitin ligase of the N-end rule pathway
J. Biol. Chem.
283
24011-24028
2008
Saccharomyces cerevisiae (P19812), Saccharomyces cerevisiae ATCC 204508 (P19812)
brenda
Li, Y.; Ozaki, T.; Kikuchi, H.; Yamamoto, H.; Ohira, M.; Nakagawara, A.
A novel HECT-type E3 ubiquitin protein ligase NEDL1 enhances the p53-mediated apoptotic cell death in its catalytic activity-independent manner
Oncogene
27
3700-3709
2008
Homo sapiens (Q76N89)
brenda
Chen, A.; Gao, B.; Zhang, J.; McEwen, T.; Ye, S.Q.; Zhang, D.; Fang, D.
The HECT-type E3 ubiquitin ligase AIP2 inhibits activation-induced T-cell death by catalyzing EGR2 ubiquitination
Mol. Cell. Biol.
29
5348-5356
2009
Homo sapiens (O00308)
brenda
Lu, K.; Li, P.; Zhang, M.; Xing, G.; Li, X.; Zhou, W.; Bartlam, M.; Zhang, L.; Rao, Z.; He, F.
Pivotal role of the C2 domain of the Smurf1 ubiquitin ligase in substrate selection
J. Biol. Chem.
286
16861-16870
2011
Homo sapiens (Q9HCE7)
brenda
Lin, D.Y.; Diao, J.; Zhou, D.; Chen, J.
Biochemical and structural studies of a HECT-like ubiquitin ligase from Escherichia coli O157:H7
J. Biol. Chem.
286
441-449
2011
Escherichia coli (A0A0H3JDV8)
brenda
Maspero, E.; Mari, S.; Valentini, E.; Musacchio, A.; Fish, A.; Pasqualato, S.; Polo S.
Structure of the HECT:ubiquitin complex and its role in ubiquitin chain elongation
EMBO Rep.
12
342-349
2011
Homo sapiens (P46934)
brenda
Kamadurai, H.B.; Qiu, Y.; Deng, A.; Harrison, J.S.; Macdonald, C.; Actis, M.; Rodrigues, P.; Miller, D.J.; Souphron, J.; Lewis, S.M.; Kurinov, I.; Fujii, N.; Hammel, M.; Piper, R.; Kuhlman, B.; Schulman, B.A.
Mechanism of ubiquitin ligation and lysine prioritization by a HECT E3
eLife
2
e00828
2013
Saccharomyces cerevisiae (P39940), Saccharomyces cerevisiae ATCC 204508 (P39940)
brenda
Hu, G.; Wang, X.; Saunders, D.; Henderson, M.; Russell, A.; Herring, B.; Zhou, J.
Modulation of myocardin function by the ubiquitin E3 ligase UBR5
J. Biol. Chem.
286
11800-11809
2011
Mus musculus (Q80TP3)
brenda
Zanier, K.; Charbonnier, S.; Baltzinger, M.; Nomine, Y.; Altschuh, D.; Trave, G.
Kinetic analysis of the interactions of human papillomavirus E6 oncoproteins with the ubiquitin ligase E6AP using surface plasmon resonance
J. Mol. Biol.
349
401-412
2005
Homo sapiens (Q05086)
brenda
Lin, Q.; Wang, J.; Childress, C.; Sudol, M.; Carey, D.; Yang, W.
HECT E3 ubiquitin ligase Nedd4-1 ubiquitinates ACK and regulates epidermal growth factor (EGF)-induced degradation of EGF receptor and ACK
Mol. Cell. Biol.
30
1541-1554
2010
Homo sapiens (P46934)
brenda
Maspero, E.; Valentini, E.; Mari, S.; Cecatiello, V.; Soffientini, P.; Pasqualato, S.; Polo, S.
Structure of a ubiquitin-loaded HECT ligase reveals the molecular basis for catalytic priming
Nat. Struct. Mol. Biol.
20
696-701
2013
Homo sapiens (P46934), Homo sapiens
brenda
Miao, Y.; Zentgraf, U.
A HECT E3 ubiquitin ligase negatively regulates Arabidopsis leaf senescence through degradation of the transcription factor WRKY53
Plant J.
63
179-188
2010
Arabidopsis thaliana (Q9SU29)
brenda
Li, Y.; Kong, Y.; Zhou, Z.; Chen, H.; Wang, Z.; Hsieh, Y.C.; Zhao, D.; Zhi, X.; Huang, J.; Zhang, J.; Li, H.; Chen, C.
The HECTD3 E3 ubiquitin ligase facilitates cancer cell survival by promoting K63-linked polyubiquitination of caspase-8
Cell Death Dis.
4
e935
2013
Homo sapiens (Q5T447)
brenda
Rossi, M.; Rotblat, B.; Ansell, K.; Amelio, I.; Caraglia, M.; Misso, G.; Bernassola, F.; Cavasotto, C.; Knight, R.; Ciechanover, A.; Melino, G.
High throughput screening for inhibitors of the HECT ubiquitin E3 ligase ITCH identifies antidepressant drugs as regulators of autophagy
Cell Death Dis.
5
e935
2014
Homo sapiens (Q96J02)
-
brenda
Wang, R.; Kaul, Z.; Ambardekar, C.; Yamamoto, T.G.; Kavdia, K.; Kodali, K.; High, A.A.; Kitagawa, R.
HECT-E3 ligase ETC-1 regulates securin and cyclin B1 cytoplasmic abundance to promote timely anaphase during meiosis in C. elegans
Development
140
2149-2159
2013
Caenorhabditis elegans
brenda
Krsmanovic, T.; Koelling, R.
The HECT E3 ubiquitin ligase Rsp5 is important for ubiquitin homeostasis in yeast
FEBS Lett.
577
215-219
2004
Saccharomyces cerevisiae (P39940), Saccharomyces cerevisiae
brenda
Nie, J.; Liu, L.; Wu, M.; Xing, G.; He, S.; Yin, Y.; Tian, C.; He, F.; Zhang, L.
HECT ubiquitin ligase Smurf1 targets the tumor suppressor ING2 for ubiquitination and degradation
FEBS Lett.
584
3005-3012
2010
Homo sapiens (Q9HCE7)
brenda
Angers, A.; Ramjaun, A.R.; McPherson, P.S.
The HECT domain ligase Itch ubiquitinates endophilin and localizes to the trans-Golgi network and endosomal system
J. Biol. Chem.
279
11471-11479
2004
Homo sapiens (Q96J02)
brenda
Park, Y.; Yoon, S.K.; Yoon, J.B.
The HECT domain of TRIP12 ubiquitinates substrates of the ubiquitin fusion degradation pathway
J. Biol. Chem.
284
1540-1549
2009
Homo sapiens (Q14669), Homo sapiens
brenda
Edwin, F.; Anderson, K.; Patel, T.B.
HECT domain-containing E3 ubiquitin ligase Nedd4 interacts with and ubiquitinates Sprouty2
J. Biol. Chem.
285
255-264
2010
Homo sapiens (P46934)
brenda
Tran, H.; Bustos, D.; Yeh, R.; Rubinfeld, B.; Lam, C.; Shriver, S.; Zilberleyb, I.; Lee, M.W.; Phu, L.; Sarkar, A.A.; Zohn, I.E.; Wertz, I.E.; Kirkpatrick, D.S.; Polakis, P.
HectD1 E3 ligase modifies adenomatous polyposis coli (APC) with polyubiquitin to promote the APC-axin interaction
J. Biol. Chem.
288
3753-3767
2013
Homo sapiens
brenda
Ding, Y.; Zhang, Y.; Xu, C.; Tao, Q.H.; Chen, Y.G.
HECT domain-containing E3 ubiquitin ligase NEDD4L negatively regulates Wnt signaling by targeting dishevelled for proteasomal degradation
J. Biol. Chem.
288
8289-8298
2013
Homo sapiens (Q96PU5)
brenda
Osmundson, E.C.; Ray, D.; Moore, F.E.; Gao, Q.; Thomsen, G.H.; Kiyokawa, H.
The HECT E3 ligase Smurf2 is required for Mad2-dependent spindle assembly checkpoint
J. Cell Biol.
183
267-277
2008
Homo sapiens
brenda
Verdecia, M.A.; Joazeiro, C.A.; Wells, N.J.; Ferrer, J.L.; Bowman, M.E.; Hunter, T.; Noel, J.P.
Conformational flexibility underlies ubiquitin ligation mediated by the WWP1 HECT domain E3 ligase
Mol. Cell
11
249-259
2003
Homo sapiens (Q9H0M0)
brenda
Downes, B.P.; Stupar, R.M.; Gingerich, D.J.; Vierstra, R.D.
The HECT ubiquitin-protein ligase (UPL) family in Arabidopsis: UPL3 has a specific role in trichome development
Plant J.
35
729-742
2003
Arabidopsis thaliana (Q6WWW4)
brenda
Aerne, B.L.; Gailite, I.; Sims, D.; Tapon, N.
Hippo stabilises its adaptor Salvador by antagonising the HECT ubiquitin ligase Herc4
PLoS ONE
10
e0131113
2015
Drosophila melanogaster, Drosophila melanogaster S2
brenda
ZeRuth, G.T.; Williams, J.G.; Cole, Y.C.; Jetten, A.M.
HECT E3 ubiquitin ligase Itch functions as a novel negative regulator of Gli-Similar 3 (Glis3) transcriptional activity
PLoS ONE
10
e0131303
2015
Rattus norvegicus
brenda
Jiang, J.; Zheng, J.; She, Y.; Jia, Z.
Expression and purification of human WWP2 HECT domain in Escherichia coli
Protein Expr. Purif.
110
95-101
2015
Homo sapiens (O00308)
brenda
Rodriguez, M.S.; Gwizdek, C.; Haguenauer-Tsapis, R.; Dargemont, C.
The HECT ubiquitin ligase Rsp5p is required for proper nuclear export of mRNA in Saccharomyces cerevisiae
Traffic
4
566-575
2003
Saccharomyces cerevisiae
brenda
Gong, W.; Zhang, X.; Zhang, W.; Li, J.; Li, Z.
Structure of the HECT domain of human WWP2
Acta Crystallogr. Sect. F
71
1251-1257
2015
Homo sapiens (O00308), Homo sapiens
brenda
Otaki, Y.; Takahashi, H.; Watanabe, T.; Funayama, A.; Netsu, S.; Honda, Y.; Narumi, T.; Kadowaki, S.; Hasegawa, H.; Honda, S.; Arimoto, T.; Shishido, T.; Miyamoto, T.; Kamata, H.; Nakajima, O.; Kubota, I.
HECT-type ubiquitin E3 ligase ITCH interacts with thioredoxin-interacting protein and ameliorates reactive oxygen species-induced cardiotoxicity
J. Am. Heart Assoc.
5
e002485
2016
Rattus norvegicus, Mus musculus
brenda
An, C.I.; Ganio, E.; Hagiwara, N.
Trip12, a HECT domain E3 ubiquitin ligase, targets Sox6 for proteasomal degradation and affects fiber type-specific gene expression in muscle cells
Skeletal Muscle
3
11
2013
Homo sapiens (Q14669), Mus musculus
brenda
Dong, S.; Liu, J.; Li, L.; Wang, H.; Ma, H.; Zhao, Y.; Zhao, J.
The HECT ubiquitin E3 ligase Smurf2 degrades my-opioid receptor 1 in the ubiquitin-proteasome system in lung epithelial cells
Am. J. Physiol. Cell Physiol.
316
C632-C640
2019
Mus musculus (A2A5Z6)
brenda
Singh, S.; Sivaraman, J.
Crystal structure of HECT domain of UBE3C E3 ligase and its ubiquitination activity
Biochem. J.
477
905-923
2020
Homo sapiens (Q15386)
brenda
Xu, Y.; Anderson, D.; Ye, Y.
The HECT domain ubiquitin ligase HUWE1 targets unassembled soluble proteins for degradation
Cell Discov.
2
16040
2016
Homo sapiens (Q7Z6Z7)
brenda
Byrne, R.; Mund, T.; Licchesi, J.
Activity-based probes for HECT E3 ubiquitin ligases
ChemBioChem
18
1415-1427
2017
Homo sapiens (Q15386), Chlorocebus aethiops
brenda
Liu, Y.; HuangFu, W.; Huang, H.; Wu, W.; Chen, Y.; Yen, Y.; Huang, H.; Nien, C.; Lai, M.; Pan, S.; Liou, J.
1,4-Naphthoquinones as inhibitors of Itch, a HECT domain-E3 ligase, and tumor growth suppressors in multiple myeloma
Eur. J. Med. Chem.
140
84-91
2017
Homo sapiens (Q96J02)
brenda
Nakatsukasa, K.; Sone, M.; Alemayehu, D.; Okumura, F.; Kamura, T.
The HECT-type ubiquitin ligase Tom1 contributes to the turnover of Spo12, a component of the FEAR network, in G2/M phase
FEBS Lett.
592
1716-1724
2018
Saccharomyces cerevisiae (Q03280)
brenda
Safdar, K.; Gu, A.; Xu, X.; Au, A.; Taylor, J.; Flibotte, S.; Moerman, D.G.; Maine, E.M.
UBR-5, a conserved HECT-type E3 ubiquitin ligase, negatively regulates notch-type signaling in Caenorhabditis elegans
G3 (Bethesda)
6
2125-2134
2016
Caenorhabditis elegans (G5EDT9), Caenorhabditis elegans
brenda
Zhu, B.; Das, S.; Mitra, S.; Farris, T.; McBride, J.
Ehrlichia chaffeensis TRP120 moonlights as a HECT E3 ligase involved in selfand host ubiquitination to influence protein interactions and stability for intracellular survival
Infect. Immun.
85
e00290
2017
Homo sapiens (Q96PU5), Ehrlichia chaffeensis
brenda
Braganza, A.; Li, J.; Zeng, X.; Yates, N.; Dey, N.; Andrews, J.; Clark, J.; Zamani, L.; Wang, X.; St Croix, C.; OSullivan, R.; Garcia-Exposito, L.; Brodsky, J.; Sobol, R.
UBE3B is a calmodulin-regulated, mitochondrion-associated E3 ubiquitin ligase
J. Biol. Chem.
292
2470-2484
2017
Homo sapiens (Q7Z3V4), Homo sapiens
brenda
Todaro, D.R.; Augustus-Wallace, A.C.; Klein, J.M.; Haas, A.L.
Oligomerization of the HECT ubiquitin ligase NEDD4-2/NEDD4L is essential for polyubiquitin chain assembly
J. Biol. Chem.
293
18192-18206
2018
Homo sapiens
brenda
Mund, T.; Pelham, H.
Substrate clustering potently regulates the activity of WW-HECT domain-containing ubiquitin ligases
J. Biol. Chem.
293
5200-5209
2018
Homo sapiens (O00308)
brenda
Singh, S.; Ng, J.; Nayak, D.; Sivaraman, J.
Structural insights into a HECT-type E3 ligase AREL1 and its ubiquitination activities in vitro
J. Biol. Chem.
294
19934-19949
2019
Homo sapiens (O15033)
brenda
Lin, Q.; Dai, Q.; Meng, H.; Sun, A.; Wei, J.; Peng, K.; Childress, C.; Chen, M.; Shao, G.; Yang, W.
The HECT E3 ubiquitin ligase NEDD4interacts with and ubiquitylates SQSTM1 for inclusion body autophagy
J. Cell Sci.
130
3839-3850
2017
Homo sapiens (P46934)
brenda
Pergolizzi, B.; Bracco, E.; Bozzaro, S.
A new HECT ubiquitin ligase regulating chemotaxis and development in Dictyostelium discoideum
J. Cell Sci.
130
551-562
2017
Dictyostelium discoideum (Q54L33)
brenda
Jaeckl, M.; Stollmaier, C.; Strohaeker, T.; Hyz, K.; Maspero, E.; Polo, S.; Wiesner, S.
beta-Sheet augmentation is a conserved mechanism of priming HECT E3 ligases for ubiquitiniquitin ligation
J. Mol. Biol.
430
3218-3233
2018
Homo sapiens (Q7Z6Z7), Homo sapiens (Q9HAU4)
brenda
Zhang, W.; Wu, K.; Sartori, M.; Kamadurai, H.; Ordureau, A.; Jiang, C.; Mercredi, P.; Murchie, R.; Hu, J.; Persaud, A.; Mukherjee, M.; Li, N.; Doye, A.; Walker, J.; Sheng, Y.; Hao, Z.; Li, Y.; Brown, K.; Lemichez, E.; Chen, J.; Tong, Y.; Harper, J.; Moffat, J.
System-wide modulation of HECT E3 ligases with selective ubiquitin variant probes
Mol. Cell.
62
121-136
2016
Homo sapiens
brenda
Wang, Z.; Liu, Z.; Chen, X.; Li, J.; Yao, W.; Huang, S.; Gu, A.; Lei, Q.; Mao, Y.; Wen, W.
A multi-lock inhibitory mechanism for fine-tuning enzyme activities of the HECT family E3 ligases
Nat. Commun.
10
3162
2019
Homo sapiens (Q9H0M0), Homo sapiens
brenda
Nair, R.M.; Seenivasan, A.; Liu, B.; Chen, D.; Lowe, E.D.; Lorenz, S.
Reconstitution and structural analysis of a HECT ligase-ubiquitin complex via an activity-based probe
ACS Chem. Biol.
16
1615-1621
2021
Homo sapiens (Q5H924)
brenda
Dudey, A.P.; Hughes, G.R.; Rigby, J.M.; Monaco, S.; Stephenson, G.R.; Storr, T.E.; Angulo, J.; Chantry, A.; Hemmings, A.M.
3,3-Diindolylmethane (DIM) a molecular scaffold for inhibition of WWP1 and WWP2, members of the NEDD4 family HECT E3 ligases
ACS Omega
10
5963-5972
2025
Homo sapiens (Q9H0M0), Homo sapiens (O00308)
brenda
Singh, S.; Machida, S.; Tulsian, N.K.; Choong, Y.K.; Ng, J.; Shankar, S.; Liu, Y.; Chandiramani, K.V.; Shi, J.; Sivaraman, J.
Structural basis for the enzymatic activity of the HACE1 HECT-Type E3 ligase through N-terminal helix dimerization
Adv. Sci. (Weinh.)
10
e2207672
2023
Homo sapiens (Q8IYU2)
brenda
Song, Y.; Song, X.; Zhang, D.; Yang, Y.; Wang, L.; Song, L.
An HECT domain ubiquitin ligase CgWWP1 regulates granulocytes proliferation in oyster Crassostrea gigas
Dev. Comp. Immunol.
123
104148
2021
Magallana gigas (K1QYN2)
brenda
Sun, L.; Zhang, H.; Li, Y.
The E3 ligase HUWE1 interacts with ubiquitin non-covalently via key residues in the HECT domain
FEBS Lett.
599
559-570
2025
Homo sapiens (Q7Z6Z7)
brenda
Fujita, S.; Tada, H.; Matsuura, Y.; Hiramoto, T.; Tanaka, M.; Shintani, T.; Gomi, K.
Glucose-induced endocytic degradation of the maltose transporter MalP is mediated through ubiquitination by the HECT-ubiquitin ligase HulA and its adaptor CreD in Aspergillus oryzae
Fungal Genet. Biol.
173
103909
2024
Aspergillus oryzae (Q2UBP1), Aspergillus oryzae ATCC 42149 (Q2UBP1)
brenda
Ike, Y.; Tomioka, M.; Iino, Y.
Involvement of HECT-type E3 ubiquitin ligase genes in salt chemotaxis learning in Caenorhabditis elegans
Genetics
220
iyac025
2022
Caenorhabditis elegans (G5EDT9), Caenorhabditis elegans (Q9GUP2), Caenorhabditis elegans (V6CLA2), Caenorhabditis elegans (Q9N2Z7), Caenorhabditis elegans (Q9BKW4), Caenorhabditis elegans (O17736)
brenda
Goto, J.; Otaki, Y.; Watanabe, T.; Kobayashi, Y.; Aono, T.; Watanabe, K.; Wanezaki, M.; Kutsuzawa, D.; Kato, S.; Tamura, H.; Nishiyama, S.; Arimoto, T.; Takahashi, H.; Shishido, T.; Watanabe, M.
HECT (Homologous to the E6-AP Carboxyl Terminus)-type ubiquitin E3 ligase ITCH attenuates cardiac hypertrophy by suppressing the Wnt/beta-catenin signaling pathway
Hypertension
76
1868-1878
2020
Mus musculus (Q8C863), Rattus norvegicus (A0A0G2K9T1)
brenda
Wang, X.; De Geyter, C.; Jia, Z.; Peng, Y.; Zhang, H.
HECTD1 regulates the expression of SNAIL Implications for epithelial?mesenchymal transition
Int. J. Oncol.
56
1186-1198
2020
Homo sapiens (Q9ULT8)
brenda
Dudey, A.P.; Rigby, J.M.; Hughes, G.R.; Stephenson, G.R.; Storr, T.E.; Chantry, A.; Hemmings, A.M.
Expanding the inhibitor space of the WWP1 and WWP2 HECT E3 ligases
J. Enzyme Inhib. Med. Chem.
39
2394895
2024
Homo sapiens (Q9H0M0), Homo sapiens (O00308)
brenda
Nuro-Gyina, P.K.; Tang, N.; Guo, H.; Yan, C.; Zeng, Q.; Waldschmidt, T.J.; Zhang, J.
HECT E3 ubiquitin ligase Nedd4 is required for antifungal innate immunity
J. Immunol.
207
868-877
2021
Mus musculus (P46935)
brenda
Jiang, H.; Miller, B.D.; Viennet, T.; Kim, H.; Lee, K.; Arthanari, H.; Cole, P.A.
Protein semisynthesis reveals plasticity in HECT E3 ubiquitin ligase mechanisms
Nat. Chem.
16
1894-1905
2024
Homo sapiens (P46934)
brenda
Tuz-Sasik, M.U.; Eravsar, E.T.K.; Kinali, M.; Ergul, A.A.; Adams, M.M.
Expression levels of SMAD specific E3 ubiquitin protein ligase 2 (Smurf2) and its interacting partners show region-specific alterations during brain aging
Neuroscience
436
46-73
2020
Danio rerio (A9JRZ0)
brenda
Ottina, E.; Panova, V.; Doglio, L.; Kazachenka, A.; Cornish, G.; Kirkpatrick, J.; Attig, J.; Young, G.R.; Litchfield, K.; Lesluyes, T.; Van Loo, P.; Swanton, C.; MacRae, J.; Tueting, T.; Kassiotis, G.
E3 ubiquitin ligase HECTD2 mediates melanoma progression and immune evasion
Oncogene
40
5567-5578
2021
Homo sapiens (Q5U5R9)
brenda
Beasley, S.A.; Kellum, C.E.; Orlomoski, R.J.; Idrizi, F.; Spratt, D.E.
An Angelman syndrome substitution in the HECT E3 ubiquitin ligase C-terminal lobe of E6AP affects protein stability and activity
PLoS ONE
15
e0235925
2020
Homo sapiens (Q05086)
brenda
Ries, L.K.; Liess, A.K.L.; Feiler, C.G.; Spratt, D.E.; Lowe, E.D.; Lorenz, S.
Crystal structure of the catalytic C-lobe of the HECT-type ubiquitin ligase E6AP
Protein Sci.
29
1550-1554
2020
Homo sapiens (Q05086), Homo sapiens (Q8IVU3)
brenda
Schukur, L.; Zimmermann, T.; Niewoehner, O.; Kerr, G.; Gleim, S.; Bauer-Probst, B.; Knapp, B.; Galli, G.G.; Liang, X.; Mendiola, A.; Reece-Hoyes, J.; Rapti, M.; Barbosa, I.; Reschke, M.; Radimerski, T.; Thoma, C.R.
Identification of the HECT E3 ligase UBR5 as a regulator of MYC degradation using a CRISPR/Cas9 screen
Sci. Rep.
10
20044
2020
Homo sapiens (O95071)
brenda
Vaughan, N.; Scholz, N.; Lindon, C.; Licchesi, J.D.F.
The E3 ubiquitin ligase HECTD1 contributes to cell proliferation through an effect on mitosis
Sci. Rep.
12
13160
2022
Homo sapiens (Q9ULT8)
brenda
Wang, F.; He, Q.; Zhan, W.; Yu, Z.; Finkin-Groner, E.; Ma, X.; Lin, G.; Li, H.
Structure of the human UBR5 E3 ubiquitin ligase
Structure
31
541-552
2023
Homo sapiens (O95071)
brenda
EXTERNAL LINKS (specific for EC-Number 2.3.2.26)
Transporter Classification Database (TCDB): 8.A.30.1.5, 8.A.30.1.2, 3.A.31.1.1, 8.A.30.1.4, 8.A.30.1.1, 3.A.25.1.1
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