BBC3 (BCL2 Binding Component 3)
PUMA, a pro-apoptotic BH3-only protein, key regulator of p53-dependent and -independent apoptosis
Gene Information Card
| Symbol | BBC3 |
|---|---|
| Full Name | BCL2 Binding Component 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.32 |
| NCBI Gene ID | 596 ncbi.nlm.nih.gov/gene/596 |
| Ensembl ID | ENSG00000105327 |
| UniProt ID | Q9BXH1 |
| OMIM ID | 605854 |
| HGNC ID | HGNC:991 |
| Aliases | PUMA, JFY-1, PUMA/JFY1 |
Description
The BBC3 gene (BCL2 Binding Component 3), also known as PUMA (p53 upregulated modulator of apoptosis), encodes a BH3-only protein that is a critical mediator of apoptosis. It is a direct transcriptional target of p53 and is induced in response to various stress signals, including DNA damage, growth factor withdrawal, and oncogene activation. The PUMA protein neutralizes anti-apoptotic BCL2 family members (e.g., BCL2, BCL-XL, MCL1) and directly activates pro-apoptotic effectors BAX and BAK, leading to mitochondrial outer membrane permeabilization and cell death. BBC3 plays a key role in tumor suppression, development, and tissue homeostasis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal Cancer | Loss of BBC3 expression or function impairs p53-dependent apoptosis, promoting tumorigenesis and chemoresistance. | NCBI Gene, OMIM, COSMIC |
| Chronic Lymphocytic Leukemia (CLL) | Epigenetic silencing or mutation of BBC3 contributes to apoptosis resistance and disease progression. | ClinVar, COSMIC |
| Breast Cancer | Reduced BBC3 expression correlates with poor prognosis and resistance to chemotherapy. | NCBI Gene, OMIM |
| Lung Cancer | Inactivation of BBC3 (e.g., by promoter methylation) allows evasion of apoptosis in non-small cell lung cancer. | COSMIC, ClinVar |
| Melanoma | Loss of PUMA expression is associated with resistance to BRAF inhibitors and poor patient outcomes. | NCBI Gene, COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Bone marrow | 9.2 | Medium |
| Small intestine | 7.1 | Low |
| Colon | 6.5 | Low |
| Lung | 4.3 | Low |
| Breast | 3.1 | Low |
| Brain | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 15.3 | High expression |
| HeLa (cervical) | 8.7 | Medium expression |
| A549 (lung) | 6.2 | Low expression |
| MCF7 (breast) | 4.5 | Low expression |
| HEK293 (embryonic kidney) | 3.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.1% | Loss of start codon, likely loss of function |
| c.25C>T (p.Arg9Trp) | Missense | <0.1% | Reduced pro-apoptotic activity |
| c.49_50del (p.Leu17fs) | Frameshift | <0.1% | Truncation, loss of function |
| c.82C>T (p.Arg28*) | Nonsense | <0.1% | Premature stop, loss of function |
| c.131G>A (p.Arg44Gln) | Missense | <0.1% | Impaired binding to BCL2 family members |
Mutation functional classification
Loss of Function (LOF)
Most reported BBC3 mutations (nonsense, frameshift, start-loss, and certain missense) result in loss of pro-apoptotic function, contributing to cancer development and therapy resistance.
Gain of Function (GOF)
No gain-of-function mutations are currently documented in BBC3.
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg44Gln) may act in a dominant-negative manner by sequestering anti-apoptotic proteins without triggering apoptosis, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• p53-dependent apoptosis (Reactome: R-HSA-111471)
• Intrinsic Pathway for Apoptosis (Reactome: R-HSA-109606)
• BCL2 family interactions (Reactome: R-HSA-111453)
• Apoptosis (KEGG: hsa04210)
• p53 signaling pathway (KEGG: hsa04115)
Protein Summary
PUMA (BBC3) is a 193-amino acid BH3-only protein localized primarily to the mitochondria. It contains a single BH3 domain essential for its pro-apoptotic function. Under stress conditions, PUMA is transcriptionally upregulated by p53 and other transcription factors. PUMA binds to and neutralizes anti-apoptotic BCL2 family members (BCL2, BCL-XL, MCL1, BCL-W, A1), releasing BAX and BAK to form pores in the mitochondrial outer membrane, leading to cytochrome c release and caspase activation. PUMA is a potent inducer of apoptosis and is critical for tumor suppression, immune response, and developmental cell death.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| BBC3 Knockout HEK293 Cell Line | EDJ-KQ1394 | Human | 27113 | Details Get a Quote |
| BBC3 Knockout A-549 Cell Line | EDJ-KQ20917 | Human | 27113 | Details Get a Quote |
| BBC3 Knockout HCT 116 Cell Line | EDJ-KQ20918 | Human | 27113 | Details Get a Quote |
| BBC3 Knockout HeLa Cell Line | EDJ-KQ20919 | Human | 27113 | Details Get a Quote |
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