ATF1: Activating Transcription Factor 1
A key bZIP transcription factor in cellular stress response, growth, and tumorigenesis
Gene Information Card
| Symbol | ATF1 |
|---|---|
| Full Name | Activating Transcription Factor 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q13.12 |
| NCBI Gene ID | 466 ncbi.nlm.nih.gov/gene/466 |
| Ensembl ID | ENSG00000123268 |
| UniProt ID | P18846 |
| OMIM ID | 123803 |
| HGNC ID | 783 |
| Aliases | TREB36, ATF-1, cAMP-dependent transcription factor ATF-1 |
Description
ATF1 (Activating Transcription Factor 1) is a member of the CREB/ATF family of basic leucine zipper (bZIP) transcription factors. It binds to the cAMP response element (CRE) and functions as a homodimer or heterodimer with other bZIP proteins (e.g., CREB, ATF2, c-Jun). ATF1 regulates the expression of genes involved in cell proliferation, survival, differentiation, and stress response. It is widely expressed and plays a critical role in integrating signals from cAMP, calcium, and growth factor pathways. Chromosomal rearrangements involving ATF1 (e.g., FUS-ATF1, EWSR1-ATF1) are oncogenic drivers in several sarcomas and melanocytic neoplasms.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Angiomatoid fibrous histiocytoma | FUS-ATF1 fusion (t(12;16)(q13;p11)) leads to constitutive activation of ATF1 transcriptional activity, driving tumorigenesis. | PMID: 10615119, NCBI |
| Clear cell sarcoma (melanoma of soft parts) | EWSR1-ATF1 fusion (t(12;22)(q13;q12)) results in chimeric protein with aberrant transcription of MITF and other targets. | PMID: 8381579, NCBI |
| Primary pulmonary myxoid sarcoma | EWSR1-ATF1 fusion identified as a recurrent genetic event. | PMID: 21702011, NCBI |
| Melanoma | ATF1 overexpression and activation via MAPK pathway contribute to melanocyte transformation and resistance to apoptosis. | PMID: 15601829, NCBI |
| Hyalinizing clear cell carcinoma of salivary gland | EWSR1-ATF1 fusion reported in a subset of cases. | PMID: 21572457, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Liver | 6.1 | Low |
| Lung | 9.7 | Low |
| Kidney | 10.2 | Low |
| Testis | 15.8 | Medium |
| Spleen | 7.4 | Low |
| Skin | 11.0 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.2 | Cervical carcinoma; high expression |
| A549 | 9.8 | Lung carcinoma; moderate expression |
| HEK293 | 11.5 | Embryonic kidney; moderate expression |
| K562 | 8.1 | Leukemia; low expression |
| MCF7 | 12.0 | Breast carcinoma; moderate 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% | Potential loss of start codon; effect unknown |
| c.100G>A (p.Glu34Lys) | Missense | <0.1% | Rare variant; uncertain significance |
| FUS-ATF1 fusion | Gene fusion | Recurrent in angiomatoid fibrous histiocytoma | Oncogenic; constitutive activation of ATF1 |
| EWSR1-ATF1 fusion | Gene fusion | Recurrent in clear cell sarcoma | Oncogenic; drives MITF expression |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations reported in disease. Knockout studies in mice show reduced viability and impaired stress response.
Gain of Function (GOF)
Gene fusions (FUS-ATF1, EWSR1-ATF1) result in gain-of-function chimeric proteins with constitutive transcriptional activity, promoting oncogenesis.
Dominant Negative (DN)
Not described for ATF1 in human disease.
View complete mutation data：
Gene Ontology (GO)
Pathways
• CREB signaling pathway (Reactome: R-HSA-111932)
• cAMP-dependent protein kinase (PKA) signaling (Reactome: R-HSA-163615)
• MAPK signaling pathway (KEGG: hsa04010)
• Melanogenesis (KEGG: hsa04916)
Protein Summary
ATF1 is a 271-amino acid transcription factor (35 kDa) containing a basic leucine zipper (bZIP) domain that mediates DNA binding and dimerization. It is predominantly nuclear and phosphorylated at Ser63 by PKA, CaMKIV, and RSK, which enhances its transcriptional activity. ATF1 regulates genes involved in cell cycle (e.g., cyclin A), survival (e.g., BCL2), and melanocyte differentiation (e.g., MITF). The protein is ubiquitously expressed with highest levels in brain and testis. Pathogenic fusions replace the N-terminal regulatory domain of ATF1 with the transactivation domain of FUS or EWSR1, leading to constitutive activation and oncogenic transformation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ATF1 Knockout HEK293 Cell Line | EDJ-KQ12464 | Human | 466 | Details Get a Quote |
| ATF1 Knockout HeLa Cell Line | EDJ-KQ40122 | Human | 466 | Details Get a Quote |
| ATF1 Knockout A-549 Cell Line | EDJ-KQ41407 | Human | 466 | Details Get a Quote |
| ATF1 Knockout HCT 116 Cell Line | EDJ-KQ41408 | Human | 466 | Details Get a Quote |
| ATF1 Knockout LoVo Cell Line | EDJ-KZ557 | Human | 466 | Details Get a Quote |
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