BTRC (Beta-Transducin Repeat Containing E3 Ubiquitin Protein Ligase)
Key regulator of β-catenin degradation and NF-κB signaling
Gene Information Card
| Symbol | BTRC |
|---|---|
| Full Name | Beta-Transducin Repeat Containing E3 Ubiquitin Protein Ligase |
| Gene Type | Protein coding |
| Chromosomal Location | 10q24.32 |
| NCBI Gene ID | 8945 ncbi.nlm.nih.gov/gene/8945 |
| Ensembl ID | ENSG00000166167 |
| UniProt ID | Q9Y297 |
| OMIM ID | 603482 |
| HGNC ID | 1144 |
| Aliases | FBXW1, FBW1A, BTRCP, FWD1, β-TrCP1, pIκBα-E3 receptor subunit |
Description
BTRC encodes beta-transducin repeat containing E3 ubiquitin protein ligase, a substrate recognition component of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex. It specifically recognizes phosphorylated substrates, including β-catenin, IκBα, and CDC25A, targeting them for ubiquitination and proteasomal degradation. BTRC plays a critical role in Wnt/β-catenin signaling, NF-κB activation, and cell cycle control. Dysregulation of BTRC is implicated in various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | Loss of BTRC function leads to β-catenin accumulation and constitutive Wnt signaling | PMID: 10521396; COSMIC mutations in colorectal tumors |
| Hepatocellular carcinoma | BTRC mutations impair β-catenin degradation, promoting tumorigenesis | PMID: 14612976; ClinVar pathogenic variants |
| Prostate cancer | BTRC overexpression correlates with NF-κB activation and metastasis | PMID: 19258504; expression data from NCBI GEO |
| Gastric cancer | BTRC downregulation stabilizes β-catenin and enhances proliferation | PMID: 20628086; immunohistochemistry studies |
| Primary immunodeficiency (EDA-ID) | BTRC gain-of-function mutations cause constitutive IκBα degradation and NF-κB activation | PMID: 23685749; OMIM #603482 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | High |
| Lymph node | 9.8 | Medium |
| Spleen | 8.2 | Medium |
| Brain (cerebellum) | 6.1 | Medium |
| Liver | 4.3 | Low |
| Heart | 3.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.2 | Embryonic kidney; high BTRC expression |
| HeLa | 8.5 | Cervical carcinoma; moderate expression |
| HCT116 | 7.1 | Colorectal carcinoma; reduced compared to normal colon |
| MCF7 | 6.8 | Breast cancer; moderate expression |
| K562 | 5.4 | Leukemia; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1250G>A (p.Arg417Gln) | Missense | 0.02% (COSMIC) | Alters substrate binding; associated with hepatocellular carcinoma |
| c.1072C>T (p.Arg358Trp) | Missense | 0.01% (COSMIC) | Reduced β-catenin degradation; found in colorectal cancer |
| c.1450_1451insA (p.Thr484Asnfs*5) | Frameshift | <0.01% (COSMIC) | Loss of function; truncation of WD40 repeats |
| c.832G>A (p.Glu278Lys) | Missense | 0.005% (ClinVar) | Gain of function; enhanced IκBα degradation; EDA-ID |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair substrate recognition (e.g., Arg358Trp) or truncate the protein (e.g., Thr484Asnfs*5) reduce β-catenin degradation, leading to Wnt pathway activation and tumorigenesis.
Gain of Function (GOF)
Mutations such as Glu278Lys enhance binding to phosphorylated IκBα, causing constitutive NF-κB activation and immunodeficiency (EDA-ID).
Dominant Negative (DN)
Not well documented; some missense variants may compete with wild-type BTRC for SCF complex assembly, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004842 - ubiquitin-protein transferase activity | • GO:0005515 - protein binding |
| • GO:0006511 - ubiquitin-dependent protein catabolic process | • GO:0000209 - protein polyubiquitination |
| • GO:0005737 - cytoplasm | • GO:0019005 - SCF ubiquitin ligase complex |
| • GO:0043161 - proteasome-mediated ubiquitin-dependent protein catabolic process | • GO:0007250 - activation of NF-κB-inducing kinase activity |
| • GO:0060070 - canonical Wnt signaling pathway |
Pathways
• Wnt/β-catenin signaling (Reactome R-HSA-201681)
• NF-κB signaling (Reactome R-HSA-975138)
• SCF ubiquitin ligase complex (Reactome R-HSA-8951664)
• Ubiquitin-mediated proteolysis (KEGG hsa04120)
• Cell cycle - G1/S transition (Reactome R-HSA-69278)
Protein Summary
BTRC (β-TrCP1) is a 569-amino acid F-box protein containing an N-terminal F-box domain for SKP1 binding and C-terminal WD40 repeats for substrate recognition. It serves as the substrate-specificity subunit of the SCFβ-TrCP E3 ubiquitin ligase complex. Key targets include phosphorylated β-catenin (Ser33/Ser37/Thr41), IκBα (Ser32/Ser36), CDC25A, and EMI1. Through ubiquitination and degradation of these substrates, BTRC regulates Wnt signaling, NF-κB activation, cell cycle progression, and DNA damage response. Alternative splicing produces multiple isoforms; the canonical isoform (UniProt Q9Y297-1) is the most studied.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| BTRC Knockout HEK293 Cell Line | EDJ-KQ281 | Human | 8945 | Details Get a Quote |
| BTRC Knockout A-549 Cell Line | EDJ-KQ18385 | Human | 8945 | Details Get a Quote |
| BTRC Knockout HCT 116 Cell Line | EDJ-KQ18386 | Human | 8945 | Details Get a Quote |
| BTRC Knockout HeLa Cell Line | EDC90409 | Human | 8945 | Details Get a Quote |
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