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2.3.2.26: HECT-type E3 ubiquitin transferase

This is an abbreviated version!
For detailed information about HECT-type E3 ubiquitin transferase, go to the full flat file.

Word Map on EC 2.3.2.26

Reaction

[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

AIP2, AIP4, apoptosis-resistant E3 ligase 1, AREL1, atrophin-1 interacting protein 2, DDB_G0286931, E3 ligase, E3 ubiquitin-protein ligase NEDD4, E3 ubiquitin-protein ligase TOM1, E6-AP, E6AP, ETC-1, HECT domain E3 ubiquitin ligase, HECT ligase, HECT-domain ubiquitin ligase, HECT-type E3 ligase, HECT-type ubiquitin E3 ligase, HECTD3, HectPH1, HECTWWP2, Herc4, Huwe1, Itch, Nedd4, Nedd4 HECT, Nedd4-1, Nedd4L, NEDL1, NleL, RSP5, Smurf1, Smurf2, sog-1, TRIP12, Trp120, UBE3B, Ube3C, ubiquitin-protein ligase E3C, UBR E3 ubiquitin ligase homolog, Ubr-5, UBR1, UBR5, UPL3, UPL5, WW domain-containing E3 Ub–protein ligase 2, WWP1, WWP2

ECTree

     2 Transferases
         2.3 Acyltransferases
             2.3.2 Aminoacyltransferases
                2.3.2.26 HECT-type E3 ubiquitin transferase

Substrates Products

Substrates Products on EC 2.3.2.26 - HECT-type E3 ubiquitin transferase

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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
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
show the reaction diagram
-
adenomatous polyposis coli protein functions as a negative regulator of the Wnt signaling pathway
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
show the reaction diagram
Dvl2 i.e. dishevelled, a central mediator for both Wnt/beta-catenin and Wnt/planar cell polarity pathways
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
show the reaction diagram
-
Glis i.e. transcription factor Gli-similar 3
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
show the reaction diagram
-
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
show the reaction diagram
ING2 i.e. candidate tumor suppressor Inhibitor of Growth 2
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
show the reaction diagram
S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [Spry2]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[Spry2]-L-lysine
show the reaction diagram
Spry2 is a regulator of receptor tyrosine kinase signaling in development and disease
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
show the reaction diagram
-
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
show the reaction diagram
S-ubiquitinyl-[Ubc-18]-L-cysteine + [IFY-1]-L-lysine
[Ubc-18]-L-cysteine + N6-ubiquitinyl-[IFY-1]-L-lysine
show the reaction diagram
-
IFY-1 i.e. anaphase inhibitor securin
-
-
?
S-ubiquitinyl-[UbcH5a]-L-cysteine + [ubiquitin mutant G76V]-L-lysine
[UbcH5a]-L-cysteine + N6-ubiquitinyl-[mutant G76V]-L-lysine
show the reaction diagram
-
-
-
?
S-ubiquitinyl-[UbcH5a]-L-cysteine + [ubiquitin-DELTAGG]-L-lysine
[UbcH5a]-L-cysteine + N6-ubiquitinyl-[ubiquitin-DELTAGG]-L-lysine
show the reaction diagram
ubiquitin-DELTAGG i.e. mutant ubiquitin lacking the two C-terminal glycine residues, cannot be conjugated to other proteins
-
-
?
S-ubiquitinyl-[UbcH7]-L-cysteine + [endophilin A]-L-lysine
[UbcH7]-L-cysteine + N6-ubiquitinyl-[endophilin A]-L-lysine
show the reaction diagram
-
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
show the reaction diagram
EGR2, a zinc finger transcription factor that has been found to regulate Fas ligand expression during activation-induced T-cell death
-
-
?
[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [Dvl2]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + [Dvl2]-N6-ubiquitinyl-L-lysine
show the reaction diagram
-
-
-
?
[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
show the reaction diagram
-
-
-
?
[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [Spo12]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + [Spo12]-N6-ubiquitinyl-L-lysine
show the reaction diagram
-
-
-
-
[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [Ubl4A]-L-lysine
[E2 ubiquitin-conjugating enzyme]-L-cysteine + [Ubl4A]-N6-ubiquitinyl-L-lysine
show the reaction diagram
Ubl4A, i.e. subunit of the Bag6 chaperone holdase complex. HUWE1 degrades unassembled Ubl4A in the cytoplasm
-
-
?
[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
show the reaction diagram
SMAC i.e. proapoptotic protein second mitochondria-derived activator of caspase
-
-
?
[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
show the reaction diagram
-
-
-
-
?
[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
show the reaction diagram
His-tagged Ube2D3, in addition the reaction mixture contains purified E1 enzyme and ubiquitin
-
-
?
[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
show the reaction diagram
SQSTM1 i.e. an autophagic cargo receptor involved in selective autophagy
-
-
?
[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
show the reaction diagram
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
-
-
?
[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
show the reaction diagram
epidermal growth factor receptor and activated Cdc42-associated tyrosine kinase are ubiquitinated by ubiquitin ligase Nedd4-1 in response to epidermal growth factor stimulation
-
-
?
[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
show the reaction diagram
[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
show the reaction diagram
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
-
-
?
[ubiquitin ligase HECTD3]-S-ubiquitin-L-cysteine + [Tara]-L-lysine
[ubiquitin ligase HECTD3]-L-cysteine + [Tara]-N6-ubiquitinyl-L-lysine
show the reaction diagram
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
-
-
?
[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
show the reaction diagram
His-tagged Ube2D3, in addition the reaction mixture contains purified E1 enzyme and ubiquitin
-
-
?
[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
show the reaction diagram
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
-
-
?
additional information
?
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