EBAG9 (Estrogen receptor-binding fragment-associated antigen 9)

2007-04-01   Ahmad Faried , Leri S. Faried 

Department of General Surgical Science (Surgery I), Graduate School of Medicine, Gunma University, Maebashi, Japan.

Identity

HGNC
LOCATION
8q23.2
LOCUSID
ALIAS
EB9,PDAF
FUSION GENES

DNA/RNA

Description

The EBAG9 gene contains 7 exons and 6 introns. It was predicted to span over approximately 24.6 kb of the genomic DNA with mRNA size approximately 1182 bp. The exon 3 was the smallest at 79 bp; the other exons ranged from 92-720 bp. The EBAG9 was isolated from MCF-7, human breast cancer cell library and it has been reported identical with RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) gene from human uterine adenocarcinoma cell line.

Transcription

The EBAG9 mRNA is up-regulated by estrogen in MCF-7 cells and its promoter responds to estrogen through the complete palindromic estrogen responsive element (ERE) that was located in the 5-up stream region of the gene.

Pseudogene

One pseudogene located in chromosome 10 associated with RCAS1/EBAG9.

Proteins

Description

The EBAG9/RCAS1 consists of 213 amino acids (aa) corresponding to a molecular weight of 24.4 kDa. The EBAG9/RCAS1 has an N-terminal trans-membrane segment (8-27 aa) and a coiled-coil structure in the C-terminal portion (179-206 aa), indicating that the EBAG9/RCAS1 is a type II membrane protein able to form oligomers through the coiled-coil structure, which is expressed on the surfaces of human cancer cells.

Expression

The EBAG9/RCAS1 mRNA is expressed in ovary, testis, prostate, thymus, muscle, and heart. At the protein level the EBAG9/RCAS1 not detected in normal ovary tissues or any of the other above. Neither mRNA nor protein was detected in small intestine, colon, lymph node or peripheral blood lymphocytes.

Localisation

Mainly in the golgi, membrane and cytoplasm of cancer tissues, but its expression is very low or hardly detected in normal tissues.

Function

The biological functions of the EBAG9/RCAS1 secreted by non-cancerous tissues remain unknown.
In cancer cells, the EBAG9/RCAS1 is a ligand for a putative receptor present on various human cell lines and normal peripheral lymphocytes such as T-, B- and natural killer (NK)-cells. The expression of this receptor is enhanced by activation of these lymphocytes. The EBAG9/RCAS1 acts to inhibit the growth of receptor-binding cells and induced apoptotic cell death. Over-expression of the EBAG9/RCAS1 is known to inhibit the growth and induced apoptosis of immune cells. As the results, cancer cells might evade immune surveillance by expressing the EBAG9/RCAS1 and inducing the apoptosis of the EBAG9/RCAS1 receptor-positive immune cells.

Homology

Mouse and human EBAG9/RCAS1 shows a high degree of homology at the amino acid level (98%). Mouse (Mus musculus) ebag9 gene spans about 30 kb in genomic DNA and consists of 7 exons. Dog (Canis familiaris) EBAG9/RCAS1 also shows highly homologues to human (96,2%) and to mouse (96,7%). For chimpanzee- (Pan troglodytes) 100%, rat- (Rattus norvegicus) 94% and chicken-ebag9 (Gallus gallus) 91%.

Mutations

Germinal

Not known in Homo sapiens.

Somatic

Not known in Homo sapiens.

Implicated in

Entity name
Immunity
Note
During pregnancy, EBAG9/RCAS1 may play a role in the down-regulation of the maternal immune response and may participate in the initiation of the labor. In the healthy women, higher EBAG9/RCAS1 expression was observed in the periovulatory and the secretory menstrual cycle phases than in the proliferation phase. The changes in EBAG9/RCAS1 expression were combined with significant differences in the number of immune cells and their activity. It suggested that EBAG9/RCAS1 endometrial expression may favor the coexistence of active lymphocytes and endometrial cells.
Disease
The elevated serum level of EBAG9/RCAS1 reported to be associated with a poor immunological prognosis in HIV-1-infected patients, and also associated with the apoptosis of CD4+ T cells in HIV infection. In addition, the induction and secretion of EBAG9/RCAS1 in HIV-Trans-acting transcriptional activator-stimulated CD4+ T cells and monocytes suggested that EBAG9/RCAS1 may involved in the CD4+ T cell apoptosis observed in HIV-1 infection along with FasL and TRAIL.
Entity name
Malignancy.
Disease
The EBAG9/RCAS1 reported to be over-expressed in many human cancers. Among them: breast, female-genital, gastrointestinal, blood, lung, pancreas, liver, renal, billiary-tract, hepatic, prostate, thyroid, gall bladder, and brain cancer.
Prognosis
The EBAG9/RCAS1 over-expression could be used as a predictor of poor prognosis in malignant diseases.
Oncogenesis
The EBAG9/RCAS1 plays a role in the immune escape of cancer cells. The EBAG9/RCAS1 could help cancer cells to survive and avoid immunosurveillance. This gene over-expression might cause progression, invasion and metastasis. The EBAG9 acts as one of the estrogen responsive genes in estrogen receptor-positive tumors and mediate estrogen function. Overall, the EBAG9/RCAS1 has an etiological role in the development and progression of cancer cells.

Bibliography

Pubmed IDLast YearTitleAuthors
108736602000Promoter analysis and chromosomal mapping of human EBAG9 gene.Ikeda K et al
172508172006RCAS1 induced by HIV-Tat is involved in the apoptosis of HIV-1 infected and uninfected CD4+ T cells.Minami R et al
104263191999Inhibition of cell growth and induction of apoptotic cell death by the human tumor-associated antigen RCAS1.Nakashima M et al
129514252003Molecular cloning of canine RCAS1 cDNA.Okamura Y et al
96264711998Tumor-associated antigen 22-1-1 expression in the uterine cervical squamous neoplasias.Sonoda K et al
113748622001Molecular cloning and characterization of mouse EBAG9, homolog of a human cancer associated surface antigen: expression and regulation by estrogen.Tsuchiya F et al
117058722001Overrepresentation of the EBAG9 gene at 8q23 associated with early-stage breast cancers.Tsuneizumi M et al
94188911998Isolation of estrogen-responsive genes with a CpG island library.Watanabe T et al
171598232006Cycle dependent RCAS1 expression with respect to the immune cells presence and activity.Wicherek L et al

Other Information

Locus ID:

NCBI: 9166
MIM: 605772
HGNC: 3123
Ensembl: ENSG00000147654

Variants:

dbSNP: 9166
ClinVar: 9166
TCGA: ENSG00000147654
COSMIC: EBAG9

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000147654ENST00000337573O00559
ENSG00000147654ENST00000337573A0A024R9E0
ENSG00000147654ENST00000395785O00559
ENSG00000147654ENST00000395785A0A024R9E0
ENSG00000147654ENST00000527709E9PND3
ENSG00000147654ENST00000529931E9PJ40
ENSG00000147654ENST00000530629E9PN10
ENSG00000147654ENST00000531677O00559
ENSG00000147654ENST00000534318E9PJ38
ENSG00000147654ENST00000614147O00559
ENSG00000147654ENST00000620557O00559
ENSG00000147654ENST00000620557A0A024R9E0

Expression (GTEx)

0
5
10
15
20
25

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
156350932005EBAG9 adds a new layer of control on large dense-core vesicle exocytosis via interaction with Snapin.19
126728042003The Golgi protein RCAS1 controls cell surface expression of tumor-associated O-linked glycan antigens.16
179816162008The biological role of the unique molecule RCAS1: a bioactive marker that induces connective tissue remodeling and lymphocyte apoptosis.11
193379742009Receptor-binding cancer antigen expressed on SiSo cells (RCAS1): a novel biomarker in the diagnosis and prognosis of human neoplasia.11
120546922002RCAS1 is associated with ductal breast cancer progression.10
128456662003EBAG9/RCAS1 expression and its prognostic significance in prostatic cancer.9
117058722001Overrepresentation of the EBAG9 gene at 8q23 associated with early-stage breast cancers.8
119924112002High expression of tumor-associated antigen RCAS1 in pancreatic ductal adenocarcinoma is an unfavorable prognostic marker.8
151641212004Expression of EBAG9/RCAS1 is associated with advanced disease in human epithelial ovarian cancer.8
218454022011The analysis of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) immunoreactivity within the microenvironment of the ovarian cancer lesion relative to the applied therapeutic strategy.8

Citation

Ahmad Faried ; Leri S. Faried

EBAG9 (Estrogen receptor-binding fragment-associated antigen 9)

Atlas Genet Cytogenet Oncol Haematol. 2007-04-01

Online version: http://atlasgeneticsoncology.org/gene/40393/ebag9