ATF5: Activating Transcription Factor 5
A key regulator of stress response, cell survival, and differentiation
Gene Information Card
| Symbol | ATF5 |
|---|---|
| Full Name | Activating Transcription Factor 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.33 |
| NCBI Gene ID | 22809 ncbi.nlm.nih.gov/gene/22809 |
| Ensembl ID | ENSG00000169136 |
| UniProt ID | Q9Y2D1 |
| OMIM ID | 606398 |
| HGNC ID | 790 |
| Aliases | ATFX, HMFN0395 |
Description
ATF5 (Activating Transcription Factor 5) is a member of the ATF/CREB family of basic leucine zipper (bZIP) transcription factors. It binds to cAMP response elements (CRE) and plays a critical role in cellular stress responses, including the unfolded protein response (UPR), amino acid deprivation, and oxidative stress. ATF5 is involved in the regulation of cell survival, proliferation, and differentiation, particularly in neural progenitor cells and various cancer types. Its expression is frequently dysregulated in glioblastoma, breast cancer, and other malignancies, where it promotes tumorigenesis and resistance to therapy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Glioblastoma | Overexpression of ATF5 promotes survival and proliferation of glioma stem-like cells; knockdown induces apoptosis | PMID: 18413744, PMID: 23319679 |
| Breast Cancer | ATF5 upregulation correlates with poor prognosis; promotes cell cycle progression and metastasis | PMID: 25609832, PMID: 27578159 |
| Hepatocellular Carcinoma | ATF5 is overexpressed and contributes to chemoresistance via anti-apoptotic signaling | PMID: 29367600 |
| Neurodevelopmental Disorders | ATF5 variants associated with intellectual disability and microcephaly; loss-of-function impairs neurogenesis | PMID: 31036916, ClinVar SCV000803123 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.3 | Low |
| Kidney | 6.1 | Low |
| Testis | 15.2 | Medium |
| Pancreas | 4.7 | Low |
| Lung | 5.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 18.4 | Embryonic kidney; high ATF5 expression |
| HeLa | 22.1 | Cervical carcinoma; elevated ATF5 |
| U87MG | 35.6 | Glioblastoma; very high ATF5 |
| MCF7 | 12.3 | Breast cancer; moderate expression |
| HepG2 | 9.8 | Hepatocellular carcinoma; moderate |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon; likely loss-of-function |
| c.502C>T (p.Arg168Trp) | Missense | 0.01% | Reduced DNA binding and transactivation |
| c.625_627del (p.Lys209del) | In-frame deletion | 0.005% | Altered dimerization; uncertain significance |
| c.784G>A (p.Gly262Arg) | Missense | 0.02% | Impaired nuclear localization; loss-of-function |
Mutation functional classification
Loss of Function (LOF)
Mutations that disrupt the bZIP domain or nuclear localization signal reduce ATF5 transcriptional activity and impair stress response, linked to neurodevelopmental phenotypes.
Gain of Function (GOF)
Amplification or overexpression of wild-type ATF5 in cancers leads to enhanced survival signaling and resistance to apoptosis; no recurrent activating point mutations reported.
Dominant Negative (DN)
Truncating or dimerization-defective mutants can interfere with wild-type ATF5 and other ATF/CREB family members, though evidence is limited to in vitro studies.
View complete mutation data：
Gene Ontology (GO)
| • GO:0003677 - DNA binding | • GO:0003700 - DNA-binding transcription factor activity |
| • GO:0005515 - protein binding | • GO:0005634 - nucleus |
| • GO:0005737 - cytoplasm | • GO:0006355 - regulation of transcription |
| • DNA-templated | • GO:0006986 - response to unfolded protein |
| • GO:0043066 - negative regulation of apoptotic process | • GO:0045664 - regulation of neuron differentiation |
Pathways
• Unfolded Protein Response (UPR) - ATF5 is induced by ER stress via PERK-eIF2α-ATF4 axis
• ATF5-mediated cell survival in cancer
• CREB/ATF signaling pathway
• Amino acid deprivation response (GCN2 pathway)
Protein Summary
ATF5 is a 282-amino acid bZIP transcription factor that localizes to the nucleus and cytoplasm. It contains a basic DNA-binding domain and a leucine zipper dimerization motif. ATF5 forms homodimers or heterodimers with other bZIP proteins (e.g., C/EBPβ, ATF4) and binds to CRE elements (TGACGTCA). It is a key effector of the integrated stress response (ISR), promoting cell survival under conditions of ER stress, nutrient deprivation, and hypoxia. In the nervous system, ATF5 is essential for maintaining neural progenitor cell identity and preventing premature differentiation. In cancer, ATF5 is frequently overexpressed and contributes to tumor growth, invasion, and chemoresistance, making it a potential therapeutic target.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ATF5 Knockout HEK293 Cell Line | EDJ-KQ2852 | Human | 22809 | Details Get a Quote |
| ATF5 Knockout A-549 Cell Line | EDJ-KQ23859 | Human | 22809 | Details Get a Quote |
| ATF5 Knockout HCT 116 Cell Line | EDJ-KQ23860 | Human | 22809 | Details Get a Quote |
| ATF5 Knockout HeLa Cell Line | EDC90507 | Human | 22809 | Details Get a Quote |
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