CBLL1

The E3 ubiquitin-protein ligase Hakai (HAKAI) also known as Casitas B-lineage lymphoma-transforming sequence-like protein 1 (CBLL1) is an is_associated_with::enzyme that in humans is encoded by the CBLL1 is_associated_with::gene. This gene encodes an is_associated_with::E3 ubiquitin ligase for the is_associated_with::E-cadherin complex and mediates its is_associated_with::ubiquitination, is_associated_with::endocytosis, and degradation in the is_associated_with::lysosomes. The encoded protein contains a RING-finger domain and is also thought to have a role in control of is_associated_with::cell proliferation.

Function
Hakai functions as a is_associated_with::RING finger domain-containing is_associated_with::E3 ubiquitin ligase for is_associated_with::E-cadherin. Hakai mediates E-cadherin is_associated_with::ubiquitination and its degradation by is_associated_with::proteasomes. "Hakai" means "destruction" in Japanese. Proteosomal degradation of E-cadherin can be regulated by is_associated_with::phosphorylation. The Hakai is_associated_with::binding site is a part of the E-cadherin cytoplasmic domain that contains several is_associated_with::tyrosines. is_associated_with::Tyrosine kinases such as Src and Met can phosphorylate E-cadherin and enhance Hakai binding to E-cadherin. Two is_associated_with::lysines of the E-cadherin cytoplasmic domain have been shown to be sites for ubiquitination. Hakai also interacts with polypyrimidine tract-binding protein-associated splicing factor.