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.^[5] 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.

CBLL1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2MQ1, 3VK6
Identifiers
Aliases	CBLL1, HAKAI, RNF188, Cbl proto-oncogene like 1
External IDs	OMIM: 606872; MGI: 2144842; HomoloGene: 11734; GeneCards: CBLL1; OMA:CBLL1 - orthologs
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7q22.3 Start 107,743,949 bp[1] End 107,761,667 bp[1]
Gene location (Mouse) Chr. Chromosome 12 (mouse)[2] Band 12|12 A2 Start 31,534,828 bp[2] End 31,549,615 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Achilles tendon epithelium of colon muscle of thigh endothelial cell bone marrow germinal epithelium bone marrow cell oocyte gastrocnemius muscle gonad Top expressed in Rostral migratory stream genital tubercle tail of embryo retinal pigment epithelium trigeminal ganglion zygote secondary oocyte lacrimal gland ciliary body lateral septal nucleus More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding metal ion binding ubiquitin protein ligase activity identical protein binding ubiquitin-protein transferase activity transferase activity zinc ion binding Cellular component ubiquitin ligase complex nucleus nucleoplasm cytosol nuclear speck cytoplasm RNA N6-methyladenosine methyltransferase complex Biological process positive regulation of cell migration negative regulation of cell adhesion positive regulation of endocytosis regulation of cell adhesion protein ubiquitination entry of bacterium into host cell cell-cell adhesion mRNA methylation multicellular organism development Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 79872 104836 Ensembl ENSG00000105879 ENSMUSG00000020659 UniProt Q75N03 Q9JIY2 RefSeq (mRNA) NM_001284291 NM_024814 NM_001253847 NM_001253848 NM_134048 RefSeq (protein) NP_001271220 NP_079090 NP_001240776 NP_001240777 NP_598809 Location (UCSC) Chr 7: 107.74 – 107.76 Mb Chr 12: 31.53 – 31.55 Mb PubMed search [3] [4]
Wikidata
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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.^[6] Tyrosine kinases such as Src and Met can phosphorylate E-cadherin and enhance Hakai binding to E-cadherin.^[7] Two lysines of the E-cadherin cytoplasmic domain have been shown to be sites for ubiquitination.^[8] Hakai also interacts with polypyrimidine tract-binding protein-associated splicing factor.^[9]

See also

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