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CITED4 (Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 4)

Written2009-08Miguel Torres-Martin, Juan Antonio Rey
Unidad de Investigacion del Hospital Universitario La Paz, Madrid, Spain

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Other aliasMRG2
LocusID (NCBI) 163732
Atlas_Id 44535
Location 1p34.2  [Link to chromosome band 1p34]
Location_base_pair Starts at and ends at bp from pter
  A. Position of CITED4 in the chromosome 1. B. Flanking genes of CITED4.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CITED4 (1p34.2) / BIN2 (12q13.13)CITED4 (1p34.2) / CCNK (14q32.2)


  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.


Note CITED4 protein is 184 amino acid long with a molecular weight of 18569 Da.
Description CITED4 has a characteristic CITED domain motif conserved in all CITED peptides located at the carboxyl-terminal domain that binds with p300/CBP.
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.
Homology CITED4 has 2 paralogues (CITED1 and CITED2) in humans. All of them belong to CITED family, found only in jawed vertebrates to date (Braganca et al., 2002).


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 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 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.


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.
Braganca J, Swingler T, Marques FI, Jones T, Eloranta JJ, Hurst HC, Shioda T, Bhattacharya S.
J Biol Chem. 2002 Mar 8;277(10):8559-65. Epub 2001 Dec 14.
PMID 11744733
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, Braganca J, Turley H, Campo L, Han C, Gatter KC, Bhattacharya S, Harris AL.
Cancer Res. 2004 Sep 1;64(17):6075-81.
PMID 15342390
Hypermethylation and transcriptional downregulation of the CITED4 gene at 1p34.2 in oligodendroglial tumours with allelic losses on 1p and 19q.
Tews B, Roerig P, Hartmann C, Hahn M, Felsberg J, Blaschke B, Sabel M, Kunitz A, Toedt G, Neben K, Benner A, von Deimling A, Reifenberger G, Lichter P.
Oncogene. 2007 Jul 26;26(34):5010-6. Epub 2007 Feb 19.
PMID 17311001
Mutational analysis of the CITED4 gene in glioblastomas.
Torres-Martin M, Franco-Hernandez C, Martinez-Glez V, de Campos JM, Isla A, Casartelli C, Rey JA.
Cancer Genet Cytogenet. 2008 Sep;185(2):114-6.
PMID 18722883
Cloning of mouse Cited4, a member of the CITED family p300/CBP-binding transcriptional coactivators: induced expression in mammary epithelial cells.
Yahata T, Takedatsu H, Dunwoodie SL, Braganca J, Swingler T, Withington SL, Hur J, Coser KR, Isselbacher KJ, Bhattacharya S, Shioda T.
Genomics. 2002 Dec;80(6):601-13.
PMID 12504852


This paper should be referenced as such :
Torres-Martin, M ; Rey, JA
CITED4 (Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 4)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(7):633-634.
Free journal version : [ pdf ]   [ DOI ]
On line version :

External links

Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)163732
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
canSAR (ICR) (select the gene name)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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