Literature summary for 2.3.2.26 extracted from

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 (2010), Mol. Cell. Biol., 30, 1541-1554.

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Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P46934	-	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
[Nedd4-1-ubiquitin-conjugating enzyme E2]-S-ubiquitin-L-cysteine + [activated Cdc42-associated tyrosine kinase]-L-lysine	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	Homo sapiens	[Nedd4-1ubiquitin-conjugating enzyme E2]-L-cysteine + [activated Cdc42-associated tyrosine kinase]-N6-ubiquitinyl-L-lysine	-	?
[Nedd4-1-ubiquitin-conjugating enzyme E2]-S-ubiquitin-L-cysteine + [epidermal growth factor receptor]-L-lysine	epidermal growth factor receptor and activated Cdc42-associated tyrosine kinase are ubiquitinated by ubiquitin ligase Nedd4-1 in response to epidermal growth factor stimulation	Homo sapiens	[Nedd4-1-ubiquitin-conjugating enzyme E2]-L-cysteine + [epidermal growth factor receptor]-N6-ubiquitinyl-L-lysine	-	?

Synonyms

Synonyms	Comment	Organism
Nedd4-1	-	Homo sapiens

General Information

General Information	Comment	Organism
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	Homo sapiens

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Release 2023.1 (January 2023)