CBLL1

Cbl proto-oncogene-like 1, E3 ubiquitin protein ligase
Identifiers
Symbols	CBLL1 ; HAKAI; RNF188
External IDs	OMIM: 606872 HomoloGene: 11734 GeneCards: CBLL1 Gene
Gene ontology Molecular function • ubiquitin-protein transferase activity • protein binding • zinc ion binding • ligase activity • identical protein binding • ubiquitin protein ligase activity Cellular component • ubiquitin ligase complex Biological process • negative regulation of cell adhesion • single organismal cell-cell adhesion • protein ubiquitination • regulation of cell adhesion • positive regulation of cell migration • positive regulation of endocytosis Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	79872	104836
Ensembl	ENSG00000105879	ENSMUSG00000020659
UniProt	Q75N03	Q9JIY2
RefSeq (mRNA)	NM_001284291	NM_001253847
RefSeq (protein)	NP_001271220	NP_001240776
Location (UCSC)	Chr 7: 107.74 – 107.76 Mb	Chr 12: 31.48 – 31.5 Mb
PubMed search

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.^[1] 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.^[2] Tyrosine kinases such as Src and Met can phosphorylate E-cadherin and enhance Hakai binding to E-cadherin.^[3] Two lysines of the E-cadherin cytoplasmic domain have been shown to be sites for ubiquitination.^[4] Hakai also interacts with polypyrimidine tract-binding protein-associated splicing factor.^[5]

See also

• CBL (gene); the gene name "CBLL1" comes from "Cbl-like protein 1"

References

1. Fujita Y, Krause G, Scheffner M, Zechner D, Leddy HE, Behrens J, Sommer T, Birchmeier W (Mar 2002). "Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex". Nature Cell Biology 4 (3): 222–31. doi:10.1038/ncb758. PMID 11836526.
2. Aparicio LA, Valladares M, Blanco M, Alonso G, Figueroa A (Jun 2012). "Biological influence of Hakai in cancer: a 10-year review". Cancer Metastasis Reviews 31 (1-2): 375–86. doi:10.1007/s10555-012-9348-x. PMC 3350634. PMID 22349934.
3. Mukherjee M, Chow SY, Yusoff P, Seetharaman J, Ng C, Sinniah S, Koh XW, Asgar NF, Li D, Yim D, Jackson RA, Yew J, Qian J, Iyu A, Lim YP, Zhou X, Sze SK, Guy GR, Sivaraman J (Mar 2012). "Structure of a novel phosphotyrosine-binding domain in Hakai that targets E-cadherin". The EMBO Journal 31 (5): 1308–19. doi:10.1038/emboj.2011.496. PMC 3298002. PMID 22252131.
4. Hartsock A, Nelson WJ (2012). "Competitive regulation of E-cadherin juxtamembrane domain degradation by p120-catenin binding and Hakai-mediated ubiquitination". PLOS ONE 7 (5): e37476. doi:10.1371/journal.pone.0037476. PMC 3365061. PMID 22693575.
5. Figueroa A, Fujita Y, Gorospe M (Nov 2009). "Hacking RNA: Hakai promotes tumorigenesis by enhancing the RNA-binding function of PSF". Cell Cycle 8 (22): 3648–51. doi:10.4161/cc.8.22.9909. PMC 2808762. PMID 19855157.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.