Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

EHF (ets homologous factor)

Written2012-04Giuseppina M Carbone, Carlo V Catapano, Domenico Albino
Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland (IOSI), Via Vela 6, Bellinzona, 6500 Switzerland

(Note : for Links provided by Atlas : click)


Alias_namesets homologous factor
Alias_symbol (synonym)ESE3
Other aliasESE3B
LocusID (NCBI) 26298
Atlas_Id 40421
Location 11p13  [Link to chromosome band 11p13]
Location_base_pair Starts at 34621041 and ends at 34663287 bp from pter ( according to hg19-Feb_2009)  [Mapping EHF.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
EHF (11p13) / ARHGAP10 (4q31.23)EHF (11p13) / EHF (11p13)EHF (11p13) / GDI2 (10p15.1)
EHF (11p13) / PDK4 (7q21.3)NAV2 (11p15.1) / EHF (11p13)NFIA (1p31.3) / EHF (11p13)
Note This gene encodes a protein that belongs to the ETS family of transcription factor. This gene belongs to the ETS subfamily defined as Epithelial Specific ETS (ESE) characterized by prevalent expression in epithelial cells. The encoded protein acts as a transcriptional repressor and/or activator. It is expressed in normal epithelium and may be involved in epithelial differentiation. Reduced expression of this gene is associated with tumorigenesis.


Note Tumor suppressor gene.
  Schematic diagram of the EHF gene comprising 9 exons (in red). The sizes in base pairs (bp) of exons (below) are shown.
Description DNA Size: 39,72 Kb, 9 exons.
Transcription See above figure B.


Description As reported by Kas et al., (J Biol Chem. 2000) sequence analysis revealed an open reading frame of 277 amino acids and a predicted molecular mass of 32,3 kDa for ESE-3a and an open reading frame encoding a 300-amino acid protein with a predicted molecular mass of 34,9 kDa for ESE-3b. In addition, several potential phosphorylation sites are present in ESE-3b including two potential protein kinase C phosphorylation sites, three casein kinase II phosphorylation sites, and one potential JNK/p38/ ERK kinase phosphorylation sites ((S/T)P) in the central region of ESE-3, just behind the alternatively spliced exon.
  Schematic representation of the two ESE3 protein isoforms. The pointed domain (PNT) and the Ets binding site (Ets DNA binding) domain are shown. PNT: (Pointed domain); EBS: (Ets binding site).
Expression Normal epithelium.
Localisation Nuclear.
Function Transcription factor that binds to DNA sequences containing the ETS factor consensus nucleotide core sequence GGAA. May act as a repressor for a specific subset of ETS/AP-1-responsive genes and as a modulator of the nuclear response to RAS and mitogen-activated protein kinase (MAPK) signaling cascades. Involved in negative regulation of the expression of EZH2 through ETS binding sequences on the EZH2 promoter in normal prostate epithelial cells, prostate cancer cells and prostate tumors. Involved in positive regulation of NKX3.1 in normal prostate epithelial cells through ETS binding site in the gene promoter. Involved in the regulation of the expression of caspase-3 through ETS binding sequences on the caspase-3 promoter in prostate cancer cells. Involved in regulation of TNFRSF10B/DR5 expression through ETS binding sequences on the TNFRSF10B/DR5 promoter. May play a role in regulating epithelial cell differentiation and contribute to development and tumorigenesis by acting as a tumor suppressor gene.


Note Unknown.
Germinal Unknown.
Somatic Unknown.

Implicated in

Entity Human malignancies
Note Albino et al. (Cancer Research, 2012) showed that ESE3, an endogenously expressed ETS transcription factor, controls prostate epithelial cell differentiation and stem-like potential. Stable ESE3 knockdown in prostate epithelial cells induced epithelial-to-mesenchymal transition (EMT), stem-like features, tumour-initiating and metastatic properties. Conversely, re-expression of ESE3 in prostate cancer cells reduced stem-like and tumorigenic potential. Mechanistically, ESE3/EHF maintains in a repressive state key EMT and Cancer stem cells (CSC) genes, including TWIST1, ZEB2, BMI1 and POU5F1, by directly binding to novel ETS binding sites identified in their promoters. Analysis of human tissue microarrays showed that reduced ESE3 expression was an early event and frequently independent of other ETS gene alterations. Analyses of multiple microarray datasets linked loss of ESE3/EHF expression to a distinct group of prostate tumors. ESE3 low tumors displayed distinctive molecular and biological characteristics, including increased expression of EMT and CSC genes and close similarity to ESE3 knockdown prostate epithelial cells. Low ESE3 expression was associated with increased biochemical recurrence and reduced overall survival after prostatectomy.
Entity Prostate cancer
Note The ESE3 expression is reduced in prostate tumors.
Disease Prostate cancer (possibly implicated in other solid tumors of epithelial origin).
Oncogenesis Cangemi et al. (Oncogene 2008) and Albino et al. (Cancer Research, 2012) propose a tumor suppressor role in prostate cancer for ESE3. Albino et al. (Cancer Research, 2012) propose the possibility to identify molecularly defined tumour subgroups based on the exclusive loss of ESE3 expression level.


ESE3/EHF controls epithelial cell differentiation and its loss leads to prostate tumors with mesenchymal and stem-like features.
Albino D, Longoni N, Curti L, Mello-Grand M, Pinton S, Civenni G, Thalmann G, D'Ambrosio G, Sarti M, Sessa F, Chiorino G, Catapano CV, Carbone GM.
Cancer Res. 2012 Jun 1;72(11):2889-900. Epub 2012 Apr 13.
PMID 22505649
Epithelial-specific transcription factor ESE-3 is involved in the development of monocyte-derived DCs.
Appel S, Bringmann A, Grunebach F, Weck MM, Bauer J, Brossart P.
Blood. 2006 Apr 15;107(8):3265-70. Epub 2005 Dec 27.
PMID 16380452
Reduced expression and tumor suppressor function of the ETS transcription factor ESE-3 in prostate cancer.
Cangemi R, Mensah A, Albertini V, Jain A, Mello-Grand M, Chiorino G, Catapano CV, Carbone GM.
Oncogene. 2008 May 1;27(20):2877-85. Epub 2007 Nov 26.
PMID 18037958
ESE-3, a novel member of an epithelium-specific ets transcription factor subfamily, demonstrates different target gene specificity from ESE-1.
Kas K, Finger E, Grall F, Gu X, Akbarali Y, Boltax J, Weiss A, Oettgen P, Kapeller R, Libermann TA.
J Biol Chem. 2000 Jan 28;275(4):2986-98.
PMID 10644770
Human chromosomal localization, tissue/tumor expression, and regulatory function of the ets family gene EHF.
Kleinbaum LA, Duggan C, Ferreira E, Coffey GP, Buttice G, Burton FH.
Biochem Biophys Res Commun. 1999 Oct 14;264(1):119-26.
PMID 10527851
ETS transcription factors control transcription of EZH2 and epigenetic silencing of the tumor suppressor gene Nkx3.1 in prostate cancer.
Kunderfranco P, Mello-Grand M, Cangemi R, Pellini S, Mensah A, Albertini V, Malek A, Chiorino G, Catapano CV, Carbone GM.
PLoS One. 2010 May 10;5(5):e10547.
PMID 20479932
ESE-3 transcription factor is involved in the expression of death receptor (DR)-5 through putative Ets sites.
Lim JH, Cho JY, Park YB, Park JW, Kwon TK.
Biochem Biophys Res Commun. 2006 Nov 24;350(3):736-41. Epub 2006 Sep 28.
PMID 17027647
Constitutive and cytokine-induced expression of the ETS transcription factor ESE-3 in the lung.
Silverman ES, Baron RM, Palmer LJ, Le L, Hallock A, Subramaniam V, Riese RJ, McKenna MD, Gu X, Libermann TA, Tugores A, Haley KJ, Shore S, Drazen JM, Weiss ST.
Am J Respir Cell Mol Biol. 2002 Dec;27(6):697-704.
PMID 12444029
Human chromosome 11 DNA sequence and analysis including novel gene identification.
Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, Dewar K, Lloyd C, Itoh T, Takeda T, Kim DW, She X, Barlow KF, Bloom T, Bruford E, Chang JL, Cuomo CA, Eichler E, FitzGerald MG, Jaffe DB, LaButti K, Nicol R, Park HS, Seaman C, Sougnez C, Yang X, Zimmer AR, Zody MC, Birren BW, Nusbaum C, Fujiyama A, Hattori M, Rogers J, Lander ES, Sakaki Y.
Nature. 2006 Mar 23;440(7083):497-500.
PMID 16554811
The epithelium-specific ETS protein EHF/ESE-3 is a context-dependent transcriptional repressor downstream of MAPK signaling cascades.
Tugores A, Le J, Sorokina I, Snijders AJ, Duyao M, Reddy PS, Carlee L, Ronshaugen M, Mushegian A, Watanaskul T, Chu S, Buckler A, Emtage S, McCormick MK.
J Biol Chem. 2001 Jun 8;276(23):20397-406. Epub 2001 Mar 19.
PMID 11259407


This paper should be referenced as such :
Carbone, GM ; Catapano, CV ; Albino, D
EHF (ets homologous factor)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(10):692-694.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 2 ]
  t(1;11)(p31;p13) NFIA/EHF
t(11;11)(p13;p15) NAV2/EHF

External links

HGNC (Hugo)EHF   3246
Entrez_Gene (NCBI)EHF  26298  ETS homologous factor
AliasesESE3; ESE3B; ESEJ
GeneCards (Weizmann)EHF
Ensembl hg19 (Hinxton)ENSG00000135373 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000135373 [Gene_View]  ENSG00000135373 [Sequence]  chr11:34621041-34663287 [Contig_View]  EHF [Vega]
ICGC DataPortalENSG00000135373
TCGA cBioPortalEHF
Genatlas (Paris)EHF
SOURCE (Princeton)EHF
Genetics Home Reference (NIH)EHF
Genomic and cartography
GoldenPath hg38 (UCSC)EHF  -     chr11:34621041-34663287 +  11p13   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)EHF  -     11p13   [Description]    (hg19-Feb_2009)
EnsemblEHF - 11p13 [CytoView hg19]  EHF - 11p13 [CytoView hg38]
Mapping of homologs : NCBIEHF [Mapview hg19]  EHF [Mapview hg38]
Gene and transcription
Genbank (Entrez)AF124438 AF124439 AF170583 AF203977 AF212848
RefSeq transcript (Entrez)NM_001206615 NM_001206616 NM_012153
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)EHF
Cluster EST : UnigeneHs.653859 [ NCBI ]
CGAP (NCI)Hs.653859
Alternative Splicing GalleryENSG00000135373
Gene ExpressionEHF [ NCBI-GEO ]   EHF [ EBI - ARRAY_EXPRESS ]   EHF [ SEEK ]   EHF [ MEM ]
Gene Expression Viewer (FireBrowse)EHF [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)26298
GTEX Portal (Tissue expression)EHF
Human Protein AtlasENSG00000135373-EHF [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9NZC4   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9NZC4  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9NZC4
Splice isoforms : SwissVarQ9NZC4
Domaine pattern : Prosite (Expaxy)ETS_DOMAIN_3 (PS50061)    PNT (PS51433)   
Domains : Interpro (EBI)EHF    Ets_dom    Pointed_dom    SAM/pointed    WHTH_DNA-bd_dom   
Domain families : Pfam (Sanger)Ets (PF00178)    SAM_PNT (PF02198)   
Domain families : Pfam (NCBI)pfam00178    pfam02198   
Domain families : Smart (EMBL)ETS (SM00413)  SAM_PNT (SM00251)  
Conserved Domain (NCBI)EHF
DMDM Disease mutations26298
Blocks (Seattle)EHF
Human Protein Atlas [tissue]ENSG00000135373-EHF [tissue]
Peptide AtlasQ9NZC4
IPIIPI00172578   IPI00034048   IPI00978017   IPI00983802   IPI00979920   IPI00977813   IPI00979958   
Protein Interaction databases
IntAct (EBI)Q9NZC4
Ontologies - Pathways
Ontology : AmiGORNA polymerase II proximal promoter sequence-specific DNA binding  transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding  DNA binding  DNA binding  DNA binding transcription factor activity  nucleus  nucleus  nucleoplasm  Golgi apparatus  transcription by RNA polymerase II  multicellular organism development  cell proliferation  epithelial cell differentiation  positive regulation of transcription, DNA-templated  positive regulation of transcription by RNA polymerase II  epithelial cell proliferation  
Ontology : EGO-EBIRNA polymerase II proximal promoter sequence-specific DNA binding  transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding  DNA binding  DNA binding  DNA binding transcription factor activity  nucleus  nucleus  nucleoplasm  Golgi apparatus  transcription by RNA polymerase II  multicellular organism development  cell proliferation  epithelial cell differentiation  positive regulation of transcription, DNA-templated  positive regulation of transcription by RNA polymerase II  epithelial cell proliferation  
NDEx NetworkEHF
Atlas of Cancer Signalling NetworkEHF
Wikipedia pathwaysEHF
Orthology - Evolution
GeneTree (enSembl)ENSG00000135373
Phylogenetic Trees/Animal Genes : TreeFamEHF
Homologs : HomoloGeneEHF
Homology/Alignments : Family Browser (UCSC)EHF
Gene fusions - Rearrangements
Fusion : MitelmanNAV2/EHF [11p15.1/11p13]  [t(11;11)(p13;p15)]  
Fusion : MitelmanNFIA/EHF [1p31.3/11p13]  [t(1;11)(p31;p13)]  
Fusion : COSMICNFIA [EHF]  -  11p13 [669]  [fusion_670]  
Fusion PortalNAV2 11p15.1 EHF 11p13 BRCA
Fusion : QuiverEHF
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerEHF [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)EHF
Exome Variant ServerEHF
ExAC (Exome Aggregation Consortium)ENSG00000135373
GNOMAD BrowserENSG00000135373
Genetic variants : HAPMAP26298
Genomic Variants (DGV)EHF [DGVbeta]
DECIPHEREHF [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisEHF 
ICGC Data PortalEHF 
TCGA Data PortalEHF 
Broad Tumor PortalEHF
OASIS PortalEHF [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICEHF  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDEHF
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 EHF
DgiDB (Drug Gene Interaction Database)EHF
DoCM (Curated mutations)EHF (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)EHF (select a term)
NCG5 (London)EHF
Cancer3DEHF(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry EHF
NextProtQ9NZC4 [Medical]
Target ValidationEHF
Huge Navigator EHF [HugePedia]
snp3D : Map Gene to Disease26298
BioCentury BCIQEHF
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD26298
Chemical/Pharm GKB GenePA27681
Clinical trialEHF
canSAR (ICR)EHF (select the gene name)
PubMed53 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Mon Jul 16 09:46:44 CEST 2018

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us