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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

(Note : for Links provided by Atlas : click)


Alias (NCBI)MRG2
HGNC Alias nametranscriptional co-activator 4
HGNC Previous name"Cbp/p300-interacting transactivator, with Glu/Asp rich carboxy-terminal domain, 4"
LocusID (NCBI) 163732
Atlas_Id 44535
Location 1p34.2  [Link to chromosome band 1p34]
Location_base_pair Starts at 40861054 and ends at 40862363 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping CITED4.png]
  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 ]

External links

HGNC (Hugo)CITED4   18696
Entrez_Gene (NCBI)CITED4    Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 4
GeneCards (Weizmann)CITED4
Ensembl hg19 (Hinxton)ENSG00000179862 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000179862 [Gene_View]  ENSG00000179862 [Sequence]  chr1:40861054-40862363 [Contig_View]  CITED4 [Vega]
ICGC DataPortalENSG00000179862
Genatlas (Paris)CITED4
SOURCE (Princeton)CITED4
Genetics Home Reference (NIH)CITED4
Genomic and cartography
GoldenPath hg38 (UCSC)CITED4  -     chr1:40861054-40862363 -  1p34.2|1p35-p34   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CITED4  -     1p34.2|1p35-p34   [Description]    (hg19-Feb_2009)
GoldenPathCITED4 - 1p34.2|1p35-p34 [CytoView hg19]  CITED4 - 1p34.2|1p35-p34 [CytoView hg38]
genome Data Viewer NCBICITED4 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)BC035496 BC052559
RefSeq transcript (Entrez)NM_133467
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)CITED4
Alternative Splicing GalleryENSG00000179862
Gene ExpressionCITED4 [ NCBI-GEO ]   CITED4 [ EBI - ARRAY_EXPRESS ]   CITED4 [ SEEK ]   CITED4 [ MEM ]
Gene Expression Viewer (FireBrowse)CITED4 [ Firebrowse - Broad ]
GenevisibleExpression of CITED4 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)163732
GTEX Portal (Tissue expression)CITED4
Human Protein AtlasENSG00000179862-CITED4 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ96RK1   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ96RK1  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ96RK1
Splice isoforms : SwissVarQ96RK1
Domains : Interpro (EBI)CITED   
Domain families : Pfam (Sanger)CITED (PF04487)   
Domain families : Pfam (NCBI)pfam04487   
Conserved Domain (NCBI)CITED4
Blocks (Seattle)CITED4
Human Protein Atlas [tissue]ENSG00000179862-CITED4 [tissue]
Peptide AtlasQ96RK1
Protein Interaction databases
IntAct (EBI)Q96RK1
Ontologies - Pathways
Ontology : AmiGOtranscription coactivator activity  transcription coactivator activity  nucleus  nucleoplasm  cytoplasm  response to estrogen  positive regulation of transcription by RNA polymerase II  
Ontology : EGO-EBItranscription coactivator activity  transcription coactivator activity  nucleus  nucleoplasm  cytoplasm  response to estrogen  positive regulation of transcription by RNA polymerase II  
REACTOMEQ96RK1 [protein]
REACTOME PathwaysR-HSA-8866907 [pathway]   
NDEx NetworkCITED4
Atlas of Cancer Signalling NetworkCITED4
Wikipedia pathwaysCITED4
Orthology - Evolution
GeneTree (enSembl)ENSG00000179862
Phylogenetic Trees/Animal Genes : TreeFamCITED4
Homologs : HomoloGeneCITED4
Homology/Alignments : Family Browser (UCSC)CITED4
Gene fusions - Rearrangements
Fusion : Fusion_HubCITED4--BIN2    CITED4--CCNK   
Fusion : QuiverCITED4
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCITED4 [hg38]
Exome Variant ServerCITED4
GNOMAD BrowserENSG00000179862
Varsome BrowserCITED4
Genomic Variants (DGV)CITED4 [DGVbeta]
DECIPHERCITED4 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisCITED4 
ICGC Data PortalCITED4 
TCGA Data PortalCITED4 
Broad Tumor PortalCITED4
OASIS PortalCITED4 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICCITED4  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DCITED4
Mutations and Diseases : HGMDCITED4
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch CITED4
DgiDB (Drug Gene Interaction Database)CITED4
DoCM (Curated mutations)CITED4 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CITED4 (select a term)
NCG6 (London) select CITED4
Cancer3DCITED4(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry CITED4
NextProtQ96RK1 [Medical]
Target ValidationCITED4
Huge Navigator CITED4 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTD
Pharm GKB GenePA38643
Clinical trialCITED4
canSAR (ICR)CITED4 (select the gene name)
DataMed IndexCITED4
PubMed13 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Thu Mar 25 19:57:35 CET 2021

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