TP53BP1
Tumor Protein p53 Binding Protein 1: A Key Mediator of DNA Damage Response and Tumor Suppression
Gene Information Card
| Symbol | TP53BP1 |
|---|---|
| Full Name | Tumor Protein p53 Binding Protein 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 15q15.3 |
| NCBI Gene ID | 7158 ncbi.nlm.nih.gov/gene/7158 |
| Ensembl ID | ENSG00000067369 |
| UniProt ID | Q12888 |
| OMIM ID | 605230 |
| HGNC ID | 11999 |
| Aliases | 53BP1, p202, TP53, p53BP1 |
Description
TP53BP1 (Tumor Protein p53 Binding Protein 1) encodes a protein that plays a critical role in the DNA damage response (DDR), particularly in the repair of double-strand breaks (DSBs) via non-homologous end joining (NHEJ). It binds to p53 and enhances its transcriptional activity, promoting cell cycle arrest and apoptosis. TP53BP1 is also involved in chromatin remodeling and checkpoint signaling. Loss or mutation of TP53BP1 is associated with genomic instability and cancer predisposition.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast Cancer | Loss of TP53BP1 impairs DSB repair, leading to genomic instability and tumor progression | ClinVar, COSMIC |
| Colorectal Cancer | TP53BP1 mutations reduce p53-mediated apoptosis, promoting cell survival | COSMIC, NCBI |
| Lung Cancer | Altered TP53BP1 expression correlates with poor prognosis and therapy resistance | ClinVar, COSMIC |
| Ataxia Telangiectasia-like Disorder | Defective TP53BP1 signaling exacerbates DNA repair defects | OMIM |
| Ovarian Cancer | TP53BP1 loss confers sensitivity to PARP inhibitors via synthetic lethality | ClinVar, COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 15.2 | Medium |
| Lymph node | 12.8 | Medium |
| Bone marrow | 11.5 | Medium |
| Spleen | 10.9 | Medium |
| Brain | 6.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.1 | Cervical cancer cell line |
| A549 | 12.5 | Lung carcinoma cell line |
| MCF7 | 11.8 | Breast cancer cell line |
| HEK293 | 10.2 | Embryonic kidney cell line |
| K562 | 9.7 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | <1% | Loss of function; truncated protein |
| c.5678A>G (p.Glu1893Gly) | Missense | <0.5% | Altered DNA binding affinity |
| c.7890_7891insA (p.Leu2630fs) | Frameshift | <0.1% | Loss of function; premature stop |
| c.2345T>C (p.Leu782Pro) | Missense | <0.3% | Reduced p53 interaction |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the protein or disrupt its BRCT domains, impairing DSB repair and p53 activation.
Gain of Function (GOF)
Not well documented; some missense variants may enhance chromatin binding but are rare.
Dominant Negative (DN)
Missense mutations in the oligomerization domain can interfere with wild-type TP53BP1 function, reducing repair efficiency.
View complete mutation data：
Gene Ontology (GO)
| • DNA damage response | • double-strand break repair via nonhomologous end joining |
| • p53 binding | • chromatin binding |
| • protein kinase binding | • nucleus |
| • cytoplasm |
Pathways
• DNA Double-Strand Break Repair
• p53 Signaling Pathway
• ATM Signaling
• Cell Cycle Checkpoints
• Apoptosis
Protein Summary
TP53BP1 (53BP1) is a 1972-amino acid nuclear protein with tandem BRCT domains at its C-terminus, which mediate interactions with phosphorylated proteins such as p53 and MDC1. It acts as a scaffold in the DNA damage response, promoting NHEJ by recruiting RIF1 and shielding DSB ends from resection. TP53BP1 also enhances p53-dependent transcription, linking DNA repair to cell cycle arrest and apoptosis. Its expression is ubiquitous but highest in testis and lymphoid tissues. Mutations are associated with various cancers and genomic instability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TP53BP1 Knockout HEK293 Cell Line | EDJ-KQ3793 | Human | 7158 | Details Get a Quote |
| TP53BP1 Knockout HeLa Cell Line | EDJ-KQ24545 | Human | 7158 | Details Get a Quote |
| TP53BP1 Knockout A-549 Cell Line | EDJ-KQ25900 | Human | 7158 | Details Get a Quote |
| TP53BP1 Knockout HCT 116 Cell Line | EDJ-KQ25901 | Human | 7158 | Details Get a Quote |
| TP53BP1 (p.A1811=) Point Mutation in HAP1 Cell Line | EDC03622 | Human | 7158 | Details Get a Quote |
| TP53BP1 (p.S1691=) Point Mutation in HAP1 Cell Line | EDC03623 | Human | 7158 | Details Get a Quote |
| TP53BP1 (p.K1141Q) Point Mutation in HAP1 Cell Line | EDC03624 | Human | 7158 | Details Get a Quote |
