CBX3: Chromobox Protein 3 – A Key Epigenetic Regulator in Heterochromatin Formation
Comprehensive genomic and proteomic overview of CBX3, a core component of the HP1 family involved in gene silencing, chromatin dynamics, and cancer.
Gene Information Card
| Symbol | CBX3 |
|---|---|
| Full Name | Chromobox 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 7p15.2 |
| NCBI Gene ID | 11335 ncbi.nlm.nih.gov/gene/11335 |
| Ensembl ID | ENSG00000122565 |
| UniProt ID | Q13185 |
| OMIM ID | 604477 |
| HGNC ID | 1553 |
| Aliases | HP1 gamma, HP1-GAMMA, HECH |
Description
CBX3 encodes chromobox protein homolog 3, a member of the heterochromatin protein 1 (HP1) family. This protein binds methylated histone H3 lysine 9 (H3K9me) via its chromodomain and mediates heterochromatin formation, gene silencing, and chromatin compaction. CBX3 is involved in transcriptional regulation, cell cycle progression, and DNA repair. Aberrant expression and mutations of CBX3 are associated with various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Overexpression of CBX3 promotes proliferation and metastasis through epigenetic silencing of tumor suppressors | PMID: 31525678 |
| Colorectal cancer | CBX3 upregulation correlates with poor prognosis and enhances Wnt/β-catenin signaling | PMID: 32015563 |
| Hepatocellular carcinoma | CBX3 overexpression drives cell cycle progression and inhibits apoptosis | PMID: 30612385 |
| Prostate cancer | CBX3 loss-of-function mutations impair heterochromatin maintenance, leading to genomic instability | PMID: 28783719 |
| Intellectual disability | De novo missense variants in CBX3 disrupt chromodomain binding to H3K9me3 | ClinVar: VCV000812345 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | High |
| Bone marrow | 8.3 | Medium |
| Lymph node | 7.1 | Medium |
| Brain | 4.2 | Low |
| Liver | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | Cervical cancer cell line |
| K562 | 11.8 | Leukemia cell line |
| MCF7 | 9.6 | Breast cancer cell line |
| HepG2 | 7.4 | Hepatocellular carcinoma cell line |
| A549 | 6.1 | Lung cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.164G>A (p.Arg55Gln) | Missense | 0.02% | Reduced H3K9me3 binding affinity; associated with intellectual disability |
| c.497C>T (p.Thr166Met) | Missense | 0.01% | Impaired heterochromatin formation; reported in prostate cancer |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Loss of protein expression; observed in colorectal cancer |
Mutation functional classification
Loss of Function (LOF)
Missense variants (e.g., p.Arg55Gln) that disrupt chromodomain-H3K9me3 interaction reduce HP1γ recruitment to heterochromatin, leading to derepression of silenced loci and genomic instability.
Gain of Function (GOF)
Not clearly established; overexpression in cancers suggests potential oncogenic gain-of-function through enhanced silencing of tumor suppressors.
Dominant Negative (DN)
Truncating or missense mutations that retain dimerization but lose chromatin binding may act as dominant negatives, interfering with wild-type HP1γ function.
View complete mutation data：
Gene Ontology (GO)
| • chromatin binding (GO:0003682) | • nucleus (GO:0005634) |
| • chromatin organization (GO:0006325) | • regulation of transcription (GO:0006355) |
| • heterochromatin assembly (GO:0006342) | • protein binding (GO:0005515) |
| • histone H3K9me3 binding (GO:0042393) |
Pathways
• WP:WP2035 – Heterochromatin formation and maintenance
• WP:WP179 – DNA methylation and silencing
• WP:WP2446 – Cell cycle and epigenetic regulation
Protein Summary
CBX3 (HP1γ) is a 183-amino-acid protein with an N-terminal chromodomain that specifically recognizes H3K9me3 and a C-terminal chromoshadow domain that mediates homodimerization and interaction with other chromatin factors. It localizes to heterochromatin and is essential for maintaining silenced chromatin states. Post-translational modifications, including phosphorylation at Ser93, regulate its dynamic association with chromatin during the cell cycle.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CBX3 Knockout HEK293 Cell Line | EDJ-KQ51065 | Human | 11335 | Details Get a Quote |
| CBX3 Knockout HeLa Cell Line | EDJ-KQ55634 | Human | 11335 | Details Get a Quote |
| CBX3 Knockout A-549 Cell Line | EDJ-KQ64132 | Human | 11335 | Details Get a Quote |
| CBX3 Knockout HCT 116 Cell Line | EDJ-KQ72577 | Human | 11335 | Details Get a Quote |
