CBLC (Cbl Proto-Oncogene C)
E3 ubiquitin-protein ligase involved in receptor tyrosine kinase downregulation and cancer signaling
Gene Information Card
| Symbol | CBLC |
|---|---|
| Full Name | Cbl Proto-Oncogene C |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.32 |
| NCBI Gene ID | 23624 ncbi.nlm.nih.gov/gene/23624 |
| Ensembl ID | ENSG00000142273 |
| UniProt ID | Q9ULV8 |
| OMIM ID | 608453 |
| HGNC ID | 15962 |
| Aliases | CBL-3, CBL-SL, RNF57 |
Description
CBLC (Cbl Proto-Oncogene C) encodes a member of the Cbl family of E3 ubiquitin-protein ligases. The protein negatively regulates receptor tyrosine kinase (RTK) signaling by promoting ubiquitination and subsequent degradation of activated RTKs. CBLC is involved in cell growth, differentiation, and oncogenesis. Mutations and altered expression of CBLC have been implicated in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lung Cancer | CBLC mutations may impair RTK downregulation, leading to sustained proliferative signaling | COSMIC; PMID: 21779513 |
| Colorectal Cancer | CBLC overexpression associated with altered EGFR trafficking and signaling | PMID: 19029980 |
| Breast Cancer | CBLC copy number alterations and expression changes linked to tumor progression | COSMIC; PMID: 23104886 |
| Myeloid Neoplasms | CBLC mutations (e.g., missense) reported in myelodysplastic syndromes and acute myeloid leukemia | ClinVar; PMID: 25659029 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 3.2 | Low |
| Breast | 2.8 | Low |
| Colon | 4.1 | Low |
| Ovary | 3.5 | Low |
| Testis | 5.0 | Medium |
| Spleen | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung adenocarcinoma) | 3.0 | Low expression |
| MCF7 (breast cancer) | 2.5 | Low expression |
| HCT116 (colorectal carcinoma) | 4.5 | Low expression |
| K562 (leukemia) | 1.8 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1111G>A (p.Gly371Arg) | Missense | <1% | Unknown; predicted to affect protein function |
| c.1250T>C (p.Leu417Pro) | Missense | <1% | Unknown; located in RING finger domain |
| c.1372C>T (p.Arg458*) | Nonsense | <1% | Loss of function; truncation |
| c.1465_1466insA (p.Thr489Asnfs*2) | Frameshift | <1% | Loss of function; premature stop |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations in CBLC are predicted to cause loss of E3 ubiquitin ligase activity, impairing RTK downregulation.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported for CBLC.
Dominant Negative (DN)
Some missense mutations in the RING finger domain may act in a dominant-negative manner by competing with wild-type CBL proteins.
View complete mutation data：
Gene Ontology (GO)
Pathways
• EGFR tyrosine kinase inhibitor resistance (KEGG hsa01521)
• Endocytosis (KEGG hsa04144)
• Ubiquitin mediated proteolysis (KEGG hsa04120)
• Signaling by Receptor Tyrosine Kinases (Reactome R-HSA-9006934)
Protein Summary
CBLC is a 474-amino acid protein containing a tyrosine kinase binding (TKB) domain, a RING finger domain, and a proline-rich region. It functions as an E3 ubiquitin-protein ligase that targets activated receptor tyrosine kinases (e.g., EGFR) for ubiquitination and degradation, thereby attenuating signaling. CBLC is predominantly cytoplasmic and is expressed at low levels in most tissues. Its role in cancer is context-dependent, with both tumor-suppressive and oncogenic properties reported.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CBLC Knockout HEK293 Cell Line | EDJ-KQ51123 | Human | 23624 | Details Get a Quote |
| CBLC Knockout HeLa Cell Line | EDJ-KQ55785 | Human | 23624 | Details Get a Quote |
| CBLC Knockout A-549 Cell Line | EDJ-KQ64280 | Human | 23624 | Details Get a Quote |
| CBLC Knockout HCT 116 Cell Line | EDJ-KQ72726 | Human | 23624 | Details Get a Quote |
