Species Human Entrez 79872 | Human Mouse Ensembl ENSG00000105879 | |
Aliases CBLL1, HAKAI, RNF188, Cbl proto-oncogene like 1 External IDs MGI: 2144842 HomoloGene: 11734 GeneCards: CBLL1 | ||
The E3 ubiquitin-protein ligase Hakai (HAKAI) also known as Casitas B-lineage lymphoma-transforming sequence-like protein 1 (CBLL1) is an enzyme that in humans is encoded by the CBLL1 gene. This gene encodes an E3 ubiquitin ligase for the E-cadherin complex and mediates its ubiquitination, endocytosis, and degradation in the lysosomes. The encoded protein contains a RING-finger domain and is also thought to have a role in control of cell proliferation.
Function
Hakai functions as a RING finger domain-containing E3 ubiquitin ligase for E-cadherin. Hakai mediates E-cadherin ubiquitination and its degradation by proteasomes. "Hakai" means "destruction" in Japanese. Proteosomal degradation of E-cadherin can be regulated by phosphorylation. The Hakai binding site is a part of the E-cadherin cytoplasmic domain that contains several tyrosines. Tyrosine kinases such as Src and Met can phosphorylate E-cadherin and enhance Hakai binding to E-cadherin. Two 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.