ETAA1: Ewing Tumor Associated Antigen 1
A key regulator of ATR-dependent DNA replication stress response
Gene Information Card
| Symbol | ETAA1 |
|---|---|
| Full Name | Ewing tumor associated antigen 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 2p13.3 |
| NCBI Gene ID | 54465 ncbi.nlm.nih.gov/gene/54465 |
| Ensembl ID | ENSG00000143942 |
| UniProt ID | Q9H6Z9 |
| OMIM ID | 609705 |
| HGNC ID | 24648 |
| Aliases | ETAA16, FLJ10858, MGC138290 |
Description
ETAA1 (Ewing tumor associated antigen 1) encodes a protein that functions as an ATR (ataxia telangiectasia and Rad3-related) activator during DNA replication stress. It directly binds single-stranded DNA and recruits ATR to stalled replication forks, promoting checkpoint signaling and genome stability. ETAA1 is also known as a tumor antigen in Ewing sarcoma.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Ewing sarcoma | ETAA1 was originally identified as a tumor antigen recognized by cytotoxic T lymphocytes in Ewing sarcoma patients. Overexpression may contribute to immune recognition. | PMID: 10679015 |
| Breast cancer | ETAA1 copy number gains and overexpression observed in breast cancer, potentially driving ATR-dependent replication stress tolerance. | COSMIC; PMID: 28481359 |
| Colorectal cancer | Somatic mutations (missense, nonsense) reported in colorectal tumors, possibly affecting ATR activation. | COSMIC; PMID: 22810696 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 18.5 | Medium |
| Bone marrow | 12.3 | Medium |
| Lymph node | 10.1 | Medium |
| Brain | 3.2 | Low |
| Liver | 1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | Embryonic kidney, moderate expression |
| HeLa | 8.7 | Cervical carcinoma, moderate expression |
| MCF7 | 6.4 | Breast cancer, moderate expression |
| A549 | 4.1 | Lung carcinoma, low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.R201* | Nonsense | <1% | Truncation, likely loss of function |
| p.E345K | Missense | <1% | Unknown functional impact |
| p.S456L | Missense | <1% | Located in ATR interaction domain, may impair ATR activation |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the protein, particularly in the ATR-binding or DNA-binding domains, are predicted to impair replication stress signaling.
Gain of Function (GOF)
Not well characterized; amplification or overexpression may enhance ATR activation and promote cancer cell survival under replication stress.
Dominant Negative (DN)
No confirmed dominant-negative mutations reported; truncations lacking the ATR-binding domain could potentially interfere with wild-type ETAA1 function.
View complete mutation data：
Gene Ontology (GO)
| • nucleus (GO:0005634) | • nucleoplasm (GO:0005654) |
| • DNA binding (GO:0003677) | • protein binding (GO:0005515) |
| • DNA duplex unwinding (GO:0032508) | • replication fork protection (GO:0048478) |
| • activation of ATR kinase activity (GO:0072431) |
Pathways
• ATR signaling in response to replication stress (Reactome: R-HSA-176187)
• DNA damage bypass (Reactome: R-HSA-73893)
• Cell cycle checkpoints (Reactome: R-HSA-69620)
Protein Summary
ETAA1 is a 926-amino acid nuclear protein that contains a conserved ATR-activating domain (AAD) and a DNA-binding domain. It binds directly to single-stranded DNA at stalled replication forks and recruits ATR via its AAD, independently of the canonical TOPBP1-mediated pathway. This alternative ATR activation mechanism is critical for maintaining genome stability under replication stress. ETAA1 is also implicated in cancer immunity as a tumor antigen.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ETAA1 Knockout HEK293 Cell Line | EDJ-KQ11422 | Human | 54465 | Details Get a Quote |
| ETAA1 Knockout A-549 Cell Line | EDJ-KQ39663 | Human | 54465 | Details Get a Quote |
| ETAA1 Knockout HCT 116 Cell Line | EDJ-KQ39664 | Human | 54465 | Details Get a Quote |
| ETAA1 Knockout HeLa Cell Line | EDJ-KQ39665 | Human | 54465 | Details Get a Quote |
