Literature summary for 2.3.2.27 extracted from

Kassenbrock, C.; Anderson, S.
Regulation of ubiquitin protein ligase activity in c-Cbl by phosphorylation-induced conformational change and constitutive activation by tyrosine to glutamate point mutations (2004), J. Biol. Chem., 279, 28017-28027.

Search for more literature for 2.3.2.27

Protein Variants

Protein Variants	Comment	Organism
Y268E	no increased activity compared to unphosphorylated wild-type	Homo sapiens
Y268F	residue Y268 is not required for phosphorylation-induced activation	Homo sapiens
Y274E	slightly increased activity compared to unphosphorylated wild-type	Homo sapiens
Y291E	no increased activity compared to unphosphorylated wild-type	Homo sapiens
Y307E	strongly increased activity compared to unphosphorylated wild-type	Homo sapiens
Y337E	strongly increased activity compared to unphosphorylated wild-type	Homo sapiens
Y371E	mutant shows constitutive E3 ubiquitin ligase activity while retaining the ability to bind epidermal growth factor receptor. The Y371E mutant also has altered protease sensitivity, resembling the proteolytic pattern seen with tyrosine-phosphorylated c-Cbl wild-type	Homo sapiens
Y371E	strongly increased activity compared to unphosphorylated wild-type	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P22681	isoform c-Cbl	-

Posttranslational Modification

Posttranslational Modification	Comment	Organism
phosphoprotein	the E3 ubiquitin ligase activity of isoform c-Cbl is negatively regulated by other domains present in the amino-terminal half of the protein, i.e. the TKB and linker helix domains, and this negative regulation is removed when the protein is phosphorylated on tyrosine residues. Tyrosine phosphorylation alters the conformation of c-Cbl. Mutation of certain conserved tyrosine residues to glutamate can constitutively activate the E3 activity of c-Cbl	Homo sapiens

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
[c-Cbl-ubiquitin-carrier protein]-S-ubiquitinyl-L-cysteine + [epidermal growth factor receptor]-L-lysine	-	Homo sapiens	[c-Cbl-ubiquitin-carrier protein]-L-cysteine + [epidermal growth factor receptor]-N6-ubiquitinyl-L-lysine	-	?

Synonyms

Synonyms	Comment	Organism
c-Cbl	-	Homo sapiens
ring-finer protein 55	-	Homo sapiens

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Release 2023.1 (January 2023)