CBLL1

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)
End	107,761,667 bp
Gene location (Mouse)
Chr.	Chromosome 12 (mouse)
End	31,549,615 bp
RNA expression pattern
	Top expressed in
	Achilles tendon; ; epithelium of colon; ; muscle of thigh; ; endothelial cell; ; bone marrow; ; germinal epithelium; ; bone marrow cells; ; 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
	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
	79872
	104836
	ENSG00000105879
	ENSMUSG00000020659
	Q75N03
	Q9JIY2
	NM_001284291; NM_024814
	NM_001253847; NM_001253848; NM_134048
	NP_001271220; NP_079090
	NP_001240776; NP_001240777; NP_598809
	Wikidata
View/Edit Human	View/Edit Mouse

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.

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]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000105879 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000020659 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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. S2CID 40423770.
^ Aparicio LA, Valladares M, Blanco M, Alonso G, Figueroa A (Jun 2012). "Biological influence of Hakai in cancer: a 10-year review". Cancer and Metastasis Reviews. 31 (1–2): 375–86. doi:10.1007/s10555-012-9348-x. PMC 3350634. PMID 22349934.
^ 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.
^ 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. Bibcode:2012PLoSO...737476H. doi:10.1371/journal.pone.0037476. PMC 3365061. PMID 22693575.
^ 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.

External links

Human CBLL1 genome location and CBLL1 gene details page in the UCSC Genome Browser.

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

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000105879 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000020659 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid11836526-5] 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. S2CID 40423770.

[pmid22349934-6] Aparicio LA, Valladares M, Blanco M, Alonso G, Figueroa A (Jun 2012). "Biological influence of Hakai in cancer: a 10-year review". Cancer and Metastasis Reviews. 31 (1–2): 375–86. doi:10.1007/s10555-012-9348-x. PMC 3350634. PMID 22349934.

[pmid22252131-7] 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.

[8] 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. Bibcode:2012PLoSO...737476H. doi:10.1371/journal.pone.0037476. PMC 3365061. PMID 22693575.

[pmid19855157-9] 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.

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v t e Enzymes: CO CS and CN ligases (EC 6.1-6.3)
6.1: Carbon-Oxygen	Aminoacyl tRNA synthetase Alanine Arginine Asparagine Aspartate Cysteine D-alanine—poly(phosphoribitol) ligase Glutamate Glutamine Glycine Histidine Isoleucine Leucine Lysine Methionine Phenylalanine Proline Serine Threonine Tryptophan Tyrosine Valine
6.2: Carbon-Sulfur	Succinyl coenzyme A synthetase Acetyl—CoA synthetase Long-chain-fatty-acid—CoA ligase
6.3: Carbon-Nitrogen	Glutamine synthetase Ubiquitin ligase Cullin Von Hippel–Lindau tumor suppressor UBE3A Mdm2 Anaphase-promoting complex UBR1 Glutathione synthetase CTP synthetase Adenylosuccinate synthase Argininosuccinate synthase Holocarboxylase synthetase GMP synthase Asparagine synthetase Carbamoyl phosphate synthetase I II Glutamate–cysteine ligase

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

CBLL1

Function

See also

References

External links

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