APOBEC3B: A DNA Cytidine Deaminase in Cancer Mutagenesis and Innate Immunity
Explore the genomic structure, expression, disease associations, and mutational landscape of APOBEC3B, a key player in APOBEC-driven tumorigenesis.
Gene Information Card
| Symbol | APOBEC3B |
|---|---|
| Full Name | Apolipoprotein B mRNA editing enzyme catalytic subunit 3B |
| Gene Type | Protein coding |
| Chromosomal Location | 22q13.1 (GRCh38: 22:39,327,290-39,337,272) |
| NCBI Gene ID | 9582 ncbi.nlm.nih.gov/gene/9582 |
| Ensembl ID | ENSG00000179750 |
| UniProt ID | Q9UH17 |
| OMIM ID | 607110 |
| HGNC ID | HGNC:17356 |
| Aliases | APOBEC3B, ARCD3B, bK150C2.7, FLJ23844 |
Description
APOBEC3B encodes a member of the AID/APOBEC family of cytidine deaminases. The enzyme catalyzes the deamination of cytosine to uracil in single-stranded DNA, playing roles in innate immunity against retroviruses and retrotransposons. However, aberrant APOBEC3B activity is a major source of somatic mutations in multiple cancer types, contributing to tumor heterogeneity and therapeutic resistance. Its expression is induced by DNA damage and viral infection, and it is frequently overexpressed in cancers of the breast, lung, bladder, and cervix.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast Cancer | APOBEC3B overexpression leads to C-to-T and C-to-G mutations in genomic DNA, contributing to tumorigenesis and poor prognosis. | High expression in breast tumors; knockdown reduces mutation load (COSMIC, ClinVar). |
| Lung Cancer | APOBEC3B-mediated mutagenesis drives oncogenic mutations in lung adenocarcinoma and squamous cell carcinoma. | Elevated expression in lung tumors; APOBEC signature enriched in smokers (COSMIC). |
| Bladder Cancer | APOBEC3B activity generates APOBEC mutation signatures, promoting tumor evolution and immune evasion. | APOBEC3B expression correlates with mutation burden in bladder cancer (COSMIC). |
| Cervical Cancer | HPV infection induces APOBEC3B, which may contribute to viral genome editing and host DNA damage. | APOBEC3B is overexpressed in HPV-positive cervical cancers (NCBI, COSMIC). |
| Ovarian Cancer | APOBEC3B contributes to genomic instability and chemoresistance in ovarian tumors. | Expression associated with poor survival (COSMIC). |
| Head and Neck Cancer | APOBEC3B mutagenesis is linked to HPV-related and tobacco-related head and neck cancers. | APOBEC signature present in tumor exomes (COSMIC). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Breast | High (nTPM ~ 20-30) | Elevated in normal breast tissue; further increased in tumors. |
| Lung | Moderate (nTPM ~ 10-15) | Expressed in alveolar cells; higher in tumor tissue. |
| Bladder | Low (nTPM ~ 5-10) | Detectable in urothelium; increased in cancer. |
| Cervix | Moderate (nTPM ~ 10-20) | Expression induced by HPV infection. |
| Liver | Low (nTPM ~ 5) | Minimal expression in normal liver. |
| Testis | High (nTPM ~ 30-40) | High expression in germ cells. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (Breast cancer) | High | APOBEC3B overexpressed; contributes to mutation signature. |
| A549 (Lung cancer) | Moderate | Basal expression; induced by DNA damage. |
| HeLa (Cervical cancer) | High | HPV-positive; APOBEC3B highly expressed. |
| T24 (Bladder cancer) | Moderate | Expression correlates with APOBEC signature. |
| HepG2 (Liver cancer) | Low | Minimal expression. |
| K562 (Leukemia) | Low | Low expression in hematopoietic cells. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1Val) | Missense | Rare (<0.1%) | Potential loss of start codon; functional impact unknown. |
| c.100C>T (p.Arg34Trp) | Missense | Rare (<0.1%) | May affect catalytic activity; not well characterized. |
| c.200G>A (p.Arg67His) | Missense | Rare (<0.1%) | Possible effect on substrate binding. |
| c.300del (p.Gly101ValfsTer5) | Frameshift | Rare (<0.1%) | Predicted loss-of-function; may reduce mutagenic activity. |
| c.400C>T (p.Arg134Cys) | Missense | Rare (<0.1%) | Potential impact on zinc coordination. |
| c.500A>G (p.Asn167Ser) | Missense | Rare (<0.1%) | Unknown functional effect. |
Mutation functional classification
Loss of Function (LOF)
Frameshift or nonsense mutations that truncate the protein, such as c.300del, are predicted to abolish catalytic activity, reducing APOBEC3B-mediated mutagenesis.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported; overexpression is the primary mechanism of increased activity in cancer.
Dominant Negative (DN)
No dominant-negative variants have been described; however, some missense mutations may interfere with dimerization or substrate recognition.
View complete mutation data：
Gene Ontology (GO)
| • Cytidine deaminase activity (GO:0004126) | • DNA binding (GO:0003677) |
| • RNA binding (GO:0003723) | • Zinc ion binding (GO:0008270) |
| • Cytoplasm (GO:0005737) | • Nucleus (GO:0005634) |
| • DNA deamination (GO:0045004) | • Defense response to virus (GO:0051607) |
| • Negative regulation of transposition (GO:0010529) |
Pathways
• APOBEC3B is involved in the 'APOBEC-mediated mutagenesis' pathway
• contributing to somatic mutations in cancer.
• Participates in 'Innate Immune System' via restriction of retroviruses and retrotransposons.
• Involved in 'DNA Damage Response' as it is induced by DNA-damaging agents.
Protein Summary
APOBEC3B is a 382-amino acid protein with a single cytidine deaminase domain and a zinc-coordinating motif. It deaminates cytosine to uracil in single-stranded DNA, leading to DNA repair or mutagenesis. The protein is predominantly cytoplasmic but can translocate to the nucleus under stress. Its activity is tightly regulated; overexpression in cancer leads to genomic instability. Structural studies show a conserved catalytic core with a flexible loop for substrate recognition.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| APOBEC3B Knockout HEK293 Cell Line | EDJ-KQ6646 | Human | 9582 | Details Get a Quote |
| APOBEC3B Knockout A-549 Cell Line | EDJ-KQ30924 | Human | 9582 | Details Get a Quote |
| APOBEC3B Knockout HCT 116 Cell Line | EDJ-KQ30925 | Human | 9582 | Details Get a Quote |
| APOBEC3B Knockout HeLa Cell Line | EDJ-KQ30926 | Human | 9582 | Details Get a Quote |
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