Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
The Database for Annotation, Visualization and Integrated Discovery
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Cbl proto-oncogene C(CBLC) Cbl proto-oncogene C(CBLC) Related Genes Homo sapiens
CHROMOSOME 19,
CYTOBAND 19q13.2,
ENSEMBL_GENE_ID ENSG00000142273,
GENERIF_SUMMARY Data demonstrate that two E3 ligases of different classes, CBLC and AIP4, can interact and cooperate to down-regulate EGFR signaling., c-Cbl is a negative regulator of hepatocyte growth factor/receptor tyrosine kinase Met signaling in B cells, mediating ubiquitination and, consequently, proteosomal degradation of Met, with a role in Met-mediated tumorigenesis., Src is a preferential target of Cbl-c for degradation, ubiquitin protein ligase activity is regulated in c-Cbl by phosphorylation-induced conformational change and constitutive activation by tyrosine to glutamate point mutations, the N terminus of Cbl-c contributes to the binding to the E2 and phosphorylation of Tyr-341 leads to a decrease in affinity and an increase in the E3 activity of Cbl-c, The ubiquitin ligase activity of Cbl-c by the direct interaction of the LIM zinc coordinating domain of Hic5 is demonstrated., This retrospective multicentre study evaluates clinical, biochemical and genetic findings in 88 cblC patients, the effects of two pathogenic missense mutations on the the catalytic activities of the human B12-processing chaperone CblC, Silencing of CBLC causes increased sensitivity to PARP1 inhibitor olaparib in breast cancer cell line models and that defective homologous recombination (HR) DNA repair is the likely cause., Data suggest that ubiquitin ligase CBLC controls mostly network organization of the Golgi Apparatus.,
OFFICIAL_GENE_SYMBOL CBLC,
SP_COMMENT domain:The N-terminus is composed of the phosphotyrosine binding (PTB) domain, a short linker region and the RING-type zinc finger. The PTB domain, which is also called TKB (tyrosine kinase binding) domain, is composed of three different subdomains: a four-helix bundle (4H), a calcium-binding EF hand and a divergent SH2 domain., domain:The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme., function:Regulator of EGFR mediated signal transduction., miscellaneous:This protein has one functional calcium-binding site., PTM:Phosphorylated on tyrosines by EGFR., similarity:Contains 1 CBL N-terminal domain., similarity:Contains 1 RING-type zinc finger., similarity:Contains 1 SH2 domain., similarity:Contains 2 EF-hand-like domains., subunit:Interacts with a restricted range of SH3 domain proteins., tissue specificity:Ubiquitous.,