EYA2: Transcriptional Coactivator and Phosphatase in Development and Disease
EYA2 (EYA Transcriptional Coactivator And Phosphatase 2) – Gene Function, Expression, and Clinical Relevance
Gene Information Card
| Symbol | EYA2 |
|---|---|
| Full Name | EYA transcriptional coactivator and phosphatase 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 20q13.12 |
| NCBI Gene ID | 2139 ncbi.nlm.nih.gov/gene/2139 |
| Ensembl ID | ENSG00000164692 |
| UniProt ID | O00167 |
| OMIM ID | 601654 |
| HGNC ID | 3520 |
| Aliases | EAB2, EYA2_HUMAN |
Description
EYA2 encodes a member of the eyes absent (EYA) family of proteins, which function as transcriptional coactivators and possess intrinsic tyrosine phosphatase activity. The protein plays critical roles in organ development, particularly in the eye, kidney, and ear, and is implicated in DNA repair, cell cycle regulation, and apoptosis. EYA2 is frequently dysregulated in various cancers, where it can act as an oncogene or tumor suppressor depending on cellular context.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Branchiootorenal syndrome 1 (BOR1) | Loss-of-function mutations in EYA2 disrupt developmental transcriptional networks, leading to branchial arch, ear, and renal anomalies. | OMIM #601653; PMID: 15146460 |
| Ovarian cancer | EYA2 overexpression promotes tumor cell proliferation and migration via enhanced transcriptional coactivation and phosphatase activity. | COSMIC; PMID: 23431147 |
| Breast cancer | EYA2 amplification and overexpression correlate with poor prognosis; the phosphatase domain dephosphorylates H2AX, impairing DNA damage repair. | PMID: 19351884; PMID: 20010870 |
| Colorectal cancer | EYA2 upregulation is associated with increased invasion and metastasis through activation of the PI3K/AKT pathway. | PMID: 26980704 |
| Lung cancer | EYA2 expression is elevated in non-small cell lung cancer and contributes to chemoresistance. | PMID: 25605245 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 8.5 | High |
| Lung | 6.2 | Medium |
| Breast | 5.1 | Medium |
| Ovary | 4.8 | Medium |
| Brain | 2.3 | Low |
| Heart | 1.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 12.4 | High expression in embryonic kidney cells |
| MCF7 | 7.8 | Moderate expression in breast cancer cell line |
| A549 | 6.5 | Moderate expression in lung cancer cell line |
| HeLa | 4.2 | Low expression in cervical cancer cell line |
| K562 | 1.1 | Very low expression in leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1003C>T (p.Arg335Ter) | Nonsense | Rare | Loss of function; associated with branchiootorenal syndrome |
| c.1489G>A (p.Gly497Arg) | Missense | Rare | Impaired phosphatase activity; reported in ovarian cancer |
| c.1654_1655insA (p.Thr552Asnfs*2) | Frameshift | Rare | Loss of function; observed in colorectal cancer |
| Amplification | Copy number gain | Frequent in breast and ovarian cancers | Increased EYA2 expression; oncogenic effect |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg335Ter, p.Thr552Asnfs*2) truncate the protein, abolishing both transcriptional coactivation and phosphatase activity, leading to developmental defects such as branchiootorenal syndrome.
Gain of Function (GOF)
Gene amplification and overexpression in breast and ovarian cancers enhance EYA2's coactivator and phosphatase functions, promoting cell proliferation, migration, and resistance to DNA damage.
Dominant Negative (DN)
Missense mutations in the phosphatase domain (e.g., p.Gly497Arg) may retain partial coactivator function while disrupting phosphatase activity, potentially interfering with wild-type EYA2 signaling in heterozygous states.
View complete mutation data：
Gene Ontology (GO)
Pathways
• DNA damage response (H2AX dephosphorylation)
• PI3K/AKT signaling pathway
• Transcriptional coactivation by EYA family
• Organ development (eye
• kidney
• ear)
Protein Summary
EYA2 is a 592-amino acid protein (UniProt O00167) containing an N-terminal transactivation domain and a C-terminal EYA domain with tyrosine phosphatase activity. It shuttles between the nucleus and cytoplasm, interacting with SIX and DACH family transcription factors to regulate developmental gene expression. The phosphatase domain dephosphorylates histone H2AX at Tyr142, modulating DNA repair and apoptosis. EYA2 is widely expressed in fetal and adult tissues, with highest levels in kidney and lung. Its dual role as a transcriptional coactivator and phosphatase makes it a key node in development and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| EYA2 Knockout HEK293 Cell Line | EDJ-KQ4571 | Human | 2139 | Details Get a Quote |
| EYA2 Knockout A-549 Cell Line | EDJ-KQ27225 | Human | 2139 | Details Get a Quote |
| EYA2 Knockout HeLa Cell Line | EDJ-KQ53183 | Human | 2139 | Details Get a Quote |
| EYA2 Knockout HCT 116 Cell Line | EDJ-KQ70146 | Human | 2139 | Details Get a Quote |
