CITED4 (Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 4)
2009-08-01 Miguel Torres-Martin , Juan Antonio Rey AffiliationUnidad de Investigacion del Hospital Universitario La Paz, Madrid, Spain
Identity
HGNC
LOCATION
1p34.2
IMAGE
LEGEND
A. Position of CITED4 in the chromosome 1. B. Flanking genes of CITED4.
LOCUSID
ALIAS
-
FUSION GENES
DNA/RNA
Coding and flanking regions of CITED4.
Description
DNA sequence is located at chromosome 1p.
Transcription
Transcription consists of a single exon without alternative splicing. mRNA: NM_133467.
Proteins
Note
CITED4 protein is 184 amino acid long with a molecular weight of 18569 Da.
NP_597724.
NP_597724.
Description
Expression
In all tissues with special intensity in heart, liver, pancreas and skeletal muscle.
Localisation
CITED4 has nuclear and cytoplasmatic location. In most cells it has a nuclear localization, but in others it was localized in nucleus and cytoplasm.
Function
Binds CBP and tumor suppressor protein EP300 by carboxy terminus domain (residues 138-184). Therefore it may be implicated in gene transcription.
As other genes of the family, CITED4 physically interacts with transcription factor AP-2.
Fox et al. (2002) showed that CITED4 blocks the binding of hypoxia-inducible factor 1alpha to p300 in their experiments made in vitro and inhibits hypoxia-inducible factor-1alpha transactivation and hypoxia-mediated reporter gene activation. That is the reason why they concluded that CITED4 might be an inhibitor of hypoxia-inducible factor 1alpha.
As other genes of the family, CITED4 physically interacts with transcription factor AP-2.
Fox et al. (2002) showed that CITED4 blocks the binding of hypoxia-inducible factor 1alpha to p300 in their experiments made in vitro and inhibits hypoxia-inducible factor-1alpha transactivation and hypoxia-mediated reporter gene activation. That is the reason why they concluded that CITED4 might be an inhibitor of hypoxia-inducible factor 1alpha.
Mutations
Note
No mutations has been reported yet, but a total of 16 polymorphisms with unknown consequences has been founded by Tews et al. (2007) and Torres-Martin et al. (2008).
Implicated in
Entity name
Oligodendroglioma
Note
CITED4 promoter is methylated in oligodendrogliomas, especially in those with 1p/19q deletions. This hypermethylation is responsible of lower levels of CITED4 mRNA expression, suggesting a way by which CITED4 is almost silenced by both hypermethylation and chromosomal deletion (Tews et al., 2007).
Prognosis
CITED4 hypermethylation in oligodendroglioma patients is similar to prognosis associated to 1p/19q deletions. Thus, CITED4 hypermethylation might be an alternative or even a confirmation of 1p/19q testing.
Entity name
Breast cancer
Note
Cytoplasmatic translocation and loss of nuclear expression has been associated with breast cancer by Fox et al. (2002). This loss may allow p300/CBP to interact with hypoxia-inducible factor 1a and oncogenes to enhance their transcriptional activity leading to an aggressive tumor phenotype (Fox et al., 2004).
Prognosis
CITED4 is located in the nucleus in normal tissue, but in breast tumors is present both nuclear and cytoplasmatic location. This characteristic might be used as prognosis factor of this kind of tumors.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 11744733 | 2002 | Human CREB-binding protein/p300-interacting transactivator with ED-rich tail (CITED) 4, a new member of the CITED family, functions as a co-activator for transcription factor AP-2. | Bragança J et al |
| 15342390 | 2004 | CITED4 inhibits hypoxia-activated transcription in cancer cells, and its cytoplasmic location in breast cancer is associated with elevated expression of tumor cell hypoxia-inducible factor 1alpha. | Fox SB et al |
| 17311001 | 2007 | Hypermethylation and transcriptional downregulation of the CITED4 gene at 1p34.2 in oligodendroglial tumours with allelic losses on 1p and 19q. | Tews B et al |
| 18722883 | 2008 | Mutational analysis of the CITED4 gene in glioblastomas. | Torres-Martín M et al |
| 12504852 | 2002 | Cloning of mouse Cited4, a member of the CITED family p300/CBP-binding transcriptional coactivators: induced expression in mammary epithelial cells. | Yahata T et al |
Other Information
Locus ID:
NCBI: 163732
MIM: 606815
HGNC: 18696
Ensembl: ENSG00000179862
Variants:
dbSNP: 163732
ClinVar: 163732
TCGA: ENSG00000179862
COSMIC: CITED4
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000179862 | ENST00000372638 | Q96RK1 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 33759374 | 2021 | CITED4 enhances the metastatic potential of lung adenocarcinoma. | 3 |
| 33759374 | 2021 | CITED4 enhances the metastatic potential of lung adenocarcinoma. | 3 |
| 29098625 | 2017 | C/EBPB-CITED4 in Exercised Heart. | 5 |
| 29098625 | 2017 | C/EBPB-CITED4 in Exercised Heart. | 5 |
| 26243458 | 2016 | CITED4 gene silencing in colorectal cancer cells modulates adherens/tight junction gene expression and reduces cell proliferation. | 10 |
| 26243458 | 2016 | CITED4 gene silencing in colorectal cancer cells modulates adherens/tight junction gene expression and reduces cell proliferation. | 10 |
| 21755341 | 2011 | Aberrant DNA methylation but not mutation of CITED4 is associated with alteration of HIF-regulated genes in breast cancer. | 8 |
| 21755341 | 2011 | Aberrant DNA methylation but not mutation of CITED4 is associated with alteration of HIF-regulated genes in breast cancer. | 8 |
| 20734064 | 2010 | A large-scale candidate gene association study of age at menarche and age at natural menopause. | 57 |
| 20734064 | 2010 | A large-scale candidate gene association study of age at menarche and age at natural menopause. | 57 |
| 18722883 | 2008 | Mutational analysis of the CITED4 gene in glioblastomas. | 1 |
| 18722883 | 2008 | Mutational analysis of the CITED4 gene in glioblastomas. | 1 |
| 17311001 | 2007 | Hypermethylation and transcriptional downregulation of the CITED4 gene at 1p34.2 in oligodendroglial tumours with allelic losses on 1p and 19q. | 19 |
| 17311001 | 2007 | Hypermethylation and transcriptional downregulation of the CITED4 gene at 1p34.2 in oligodendroglial tumours with allelic losses on 1p and 19q. | 19 |
| 15342390 | 2004 | CITED4 inhibits hypoxia-activated transcription in cancer cells, and its cytoplasmic location in breast cancer is associated with elevated expression of tumor cell hypoxia-inducible factor 1alpha. | 31 |
Citation
Miguel Torres-Martin ; Juan Antonio Rey
CITED4 (Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 4)
Atlas Genet Cytogenet Oncol Haematol. 2009-08-01
Online version: http://atlasgeneticsoncology.org/gene/44535/cited4-(cbp-p300-interacting-transactivator-with-glu-asp-rich-carboxy-terminal-domain-4)
