Eyes absent homolog 4 Antibodies

Eyes absent homolog 4 (EYA4)

Tyrosine phosphatase that specifically dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph). 'Tyr-142' phosphorylation of histone H2AX plays a central role in DNA repair and functions as a mark that distinguishes between apoptotic and repair responses to genotoxic stress.

Promotes efficient DNA repair by dephosphorylating H2AX, promoting the recruitment of DNA repair complexes containing MDC1. Its role as histone phosphatase probably explains its role in transcription regulation during organogenesis.

Gene Information

Human
Gene Name:	EYA4
Uniprot:	O95677
Entrez:	2070

Family

Belongs to:
HAD-like hydrolase superfamily

Alternative Names

CMD1J; DFNA10; dJ78N10.1 (eyes absent); EC 3.1.3.48; eyes absent (Drosophila) homolog 4; eyes absent homolog 4 (Drosophila); eyes absent homolog 4

Molecular Weight

Mass (kDA):
69.505 kDA

Genomic Context

Human
Location:	6q23.2
Sequence:	6; NC_000006.12 (133240340..133532128)

Tissue Specificity

Highly expressed in heart and skeletal muscle.

Subcellular Localizations

Cytoplasm. Nucleus.

Diseases

• Sensorineural Hearing Loss (disorder)
• Malignant Neoplasms
• Neoplasms
• Complete Hearing Loss
• Carcinoma
• Ear Inflammation
• Haploinsufficiency
• Arthritis
• Colorectal Neoplasms
• Otitis Media
• Innate Immune Response
• Cardiomyopathy, Dilated

• Cardiomyopathies
• Adenoma
• Dysplasia
• Rheumatoid Arthritis
• Esophageal Neoplasms
• Adenocarcinoma
• Heart Failure

Pathways

• Methylation
• Dna Methylation
• Immune Response
• System Development
• Innate Immune Response
• Cell Proliferation
• Localization
• Cell Death
• Cell Adhesion
• Inner Ear Morphogenesis
• Dna Hypermethylation
• Gene Silencing
• Programmed Cell Death

• Dna Hypomethylation
• Skin Development
• Inner Ear Development
• Ear Morphogenesis
• Keratinocyte Differentiation
• Translation
• Somitogenesis

PTMs

• Methylation

• Demethylation

• Phosphorylation

Research Areas

• Vision

For details, visit:
bosterbio.com/bosterbio-gene-info-cards/EYA4

Best Uses Of The EYA4 Marker

In 1993, Steven Boster developed his first product, earning him the nickname, "he who converts science in the lavatory." Since then, he has developed hundreds of primary antibodies and has built one of the largest catalog antibody companies in China. In the late 90s, he developed a proprietary ELISA platform, PicoKine(tm). This proprietary platform allows Boster Bio to develop and deliver high-sensitivity ELISA kits.

Molecular prognostic marker for ICC

EYA4 is a potential molecular prognostic marker for ICC. Overexpression of this gene is associated with poor outcomes and was independently associated with patients' response to hepatectomy. It is also thought to be involved in tumorigenesis and function as a molecular prognostic marker for ICC. Further studies are needed to determine whether EYA4 can be useful in predicting prognosis in patients with ICC.

Using RNA-sequencing data from the TCGA, we sought to determine whether CDKN2B-AS1/ANRIL expression was clinically relevant in predicting patient survival. We estimated OS and DFS for each group using the Kaplan-Meier method, and we used a log-rank test to evaluate differences in survival between groups. We enrolled 39 patients with ICC, all undergoing liver resection with curative intent.

The study also investigated the role of SEZ6L2 as an independent prognostic marker for ICC. This marker was found to predict OS and DFS in ICC patients based on Cox regression analysis. The level of SEZ6L2 correlated with TNM stage, medical complications, and length of survival. Further research should focus on identifying the molecular mechanisms of SEZ6L2 in ICC.

In a previous study, researchers identified CA242 as a potential molecular prognostic marker for ICC. CA242 is a carbohydrate antigen that has been used as a tumor marker in several types of cancer. In the combination of a-fetoprotein (-) and CA242, both proteins showed high specificity and accuracy and differentiated ICC from HCC.

Currently, no consensus has been reached on the best way to stratify ICC patients to ensure the best possible outcome. Various research studies, however, have identified hepatic cholangiocarcinoma as a high risk group. Patients were excluded from the study if they had multiple tumors. Those without sufficient clinicopathological data were also excluded from the study. Further research is required to understand the underlying mechanisms of ICC progression and to develop new therapeutic strategies.

Using a multivariate analysis, the results of the study show that GISTs are thought to be a result of ICCs that have differentiated into pacemaker cells. Interestingly, both cell types express the CD34 protein. In the case of ICC, these cellular types also express KIT protein. These differences are important, as GISTs are often the result of accidentally dispersed ICC cells during embryogenesis.

Tumor-suppressive effect on ICC cell growth

Researchers recently reported that tumors bearing an increased EYA4 protein and mRNA content had better overall and disease-free survival than those without. Interestingly, EYA4 expression was also an independent prognostic factor for patients with HCC. These findings suggest that EYA4 overexpression inhibits ICC cell growth and prevents tumor foci formation. Further, intra-tumoral injection of EYA4 expressing plasmids significantly inhibited ICC growth in a murine xenograft model.

The authors used human ICC cell lines obtained from the Cell Resources Center of the Chinese Academy of Sciences. The cells were cultured in RPMI-1640 (Gibco BRL, Rockville, MD, USA) supplemented with 10% fetal bovine serum. To confirm the results, the cells were stained using EYA4 antigen-specific antibodies against the GAPDH gene.

The authors of the current study include Carvalho, Diana A., Zanitti, M. H. R., and Felicidade, B. L. Cruz, AndrA(c) L., Rantin, Francisco T., Dias, E. W., and Leite, Cleo A. C.

In addition to highlighting the role of EYA4 in cancer, Boster's gene infographics feature basic information about each gene. They cover the genes in both mouse and human, and their transcriptional regulation is explained by the gene-coding sequences. The gene search bar allows users to quickly locate a particular gene they're interested in. The interactive gene infographics help researchers identify genes responsible for tumor-suppression.

The authors conclude that the effect of EYA4 is independent of tumors' size, and that the effect of Boster Bio's antibody on tumor-suppressive effect of EYA4 on ICC cells is independent of the immune system. Their findings suggest that the inhibitory effect of EYA4 on ICC cell growth is mediated by inhibition of ribosomal RNA synthesis and inactivation of KI-67 antigen.

GAR domain is necessary for the efficient localization of nucleolin in nucleoli. MT binding requires methylation, but methylation does not affect the nucleolar localization of nucleolin. These studies reveal that the GAR domain is essential for efficient nucleolar localization. Therefore, a tumor-suppressive drug may be beneficial in this scenario.

High level of inactivation biallelically in sporadic lung cancer

The genetic association between familial and sporadic lung cancer is not yet clear, but a new study has suggested that EYA4 plays a role in lung cancer. Inactivation of the EYA4 gene promotes an impaired response to DNA damaging agents such as cigarette smoke. However, further studies are needed to determine the exact role of EYA4 in lung carcinogenesis.

DNA repair genes affect cellular detoxification enzymes and cell susceptibility to mutagenesis. DNA methylation of DNA repair genes may lead to genetic inactivation. Specifically, DNA methylation of 6-O-methylguanine DNA methyltransferase causes inactivation of a gene. This DNA methylation may also contribute to the increased occurrence of mutations of the RAS gene. High-level inactivation biallelically in lung cancer may be related to polymorphisms of these genes.

BRG1 is the most common gene altered in NSCLC. One-third of NSCLC cells harbor altered BRG1 gene. BRG1 mutations are typically biallelic and result in frameshifts, indels, and nonsense/missense mutations. However, the mutations can cause cancer cells to produce a protein with reduced activity or become truncated.