CBLL1

CBLL1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
Aliases CBLL1, HAKAI, RNF188, Cbl proto-oncogene like 1
External IDs MGI: 2144842 HomoloGene: 11734 GeneCards: CBLL1
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 HumanView/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]

See also

References

  1. ↑ "Human PubMed Reference:".
  2. ↑ "Mouse PubMed Reference:".
  3. ↑ 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.
  4. ↑ 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 3350634Freely accessible. PMID 22349934.
  5. ↑ 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 3298002Freely accessible. PMID 22252131.
  6. ↑ 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 3365061Freely accessible. PMID 22693575.
  7. ↑ 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 2808762Freely accessible. PMID 19855157.

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

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.