Literature summary for 2.3.2.26 extracted from

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 (2011), EMBO Rep., 12, 342-349.

Crystallization (Commentary)

Crystallization (Comment)	Organism
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	Homo sapiens

Crystallization (Comment)

Organism

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

Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
F707A	Nedd4 mutant, almost abolished HECTNedd4 binding to Lys 63 ubiquitin. Mutant F707A has defective chain elongation on substrate or shorter free chains	Homo sapiens
Y605A	Nedd4 mutant, almost abolished HECTNedd4 binding to Lys 63 ubiquitin	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P46934	-	-

Reaction

Reaction	Comment	Organism	Reaction ID
[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	Homo sapiens	a

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
additional information	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	Homo sapiens	?	-	?
additional information	Nedd4 has a strong preference for building Lys63 ubiquitin-chains on substrates. Mutant F707A has defective chain elongation on substrate or shorter free chains	Homo sapiens	?	-	?
[HECT-E3-ubiquitin-carrier protein NEDD4]-S-ubiquitin-L-cysteine + [gamma-epithel Na+-channel]-L-lysine	His-tagged Ube2D3, in addition the reaction mixture contains purified E1 enzyme and ubiquitin	Homo sapiens	[HECT-E3-ubiquitin-carrier protein NEDD4]-L-cysteine + [gamma-epithel Na+-channel]-N6-ubiquinyl-L-lysine	-	?
[ubiquitin-conjugating enzyme E2D3]-S-ubiquitin-L-cysteine + [latent membrane protein 2A LMP2A]-L-lysine	His-tagged Ube2D3, in addition the reaction mixture contains purified E1 enzyme and ubiquitin	Homo sapiens	[ubiquitin-conjugating enzyme E2D3]-L-cysteine + [latent membrane protein 2A LMP2A]-N6-ubiquitinyl-L-lysine	-	?

Synonyms

Synonyms	Comment	Organism
E3 ligase	-	Homo sapiens
E3 ubiquitin-protein ligase NEDD4	-	Homo sapiens
HECT ligase	-	Homo sapiens
Nedd4	-	Homo sapiens
Nedd4 HECT	-	Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
37	-	assay at	Homo sapiens

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7.6	-	assay at	Homo sapiens