CBLL1

Available structures

Ortholog search: PDBe RCSB

List of PDB id codes
2MQ1, 3VK6

Identifiers

Aliases

CBLL1, HAKAI, RNF188, Cbl proto-oncogene like 1

External IDs

MGI: 2144842 HomoloGene: 11734 GeneCards: CBLL1

Gene ontology
Molecular function	• zinc ion binding • ligase activity • protein binding • metal ion binding • ubiquitin protein ligase activity • identical protein binding • ubiquitin-protein transferase activity • nucleic acid binding
Cellular component	• ubiquitin ligase complex • nuclear speck • nucleus • nucleoplasm
Biological process	• positive regulation of cell migration • single organismal cell-cell adhesion • negative regulation of cell adhesion • positive regulation of endocytosis • regulation of cell adhesion • protein ubiquitination
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_001271220.1 NP_079090.2


NP_001240776.1 NP_001240777.1 NP_598809.1

Location (UCSC)

Chr 7: 107.74 – 107.76 Mb

Chr 12: 31.48 – 31.5 Mb

PubMed search

^[1]

^[2]

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.^[3] 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.^[4] Tyrosine kinases such as Src and Met can phosphorylate E-cadherin and enhance Hakai binding to E-cadherin.^[5] Two lysines of the E-cadherin cytoplasmic domain have been shown to be sites for ubiquitination.^[6] Hakai also interacts with polypyrimidine tract-binding protein-associated splicing factor.^[7]

References

↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
↑ 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.
↑ 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.
↑ 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. 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.

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

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

Enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list)

This article is issued from Wikipedia - version of the 5/19/2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.

CBLL1

Function

See also

References