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EHF (ets homologous factor)

Identity

Other namesESE3
ESE3B
ESEJ
HGNC (Hugo) EHF
LocusID (NCBI) 26298
Location 11p13
Location_base_pair Starts at 34642588 and ends at 34684834 bp from pter ( according to hg19-Feb_2009)  [Mapping]
 
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.

DNA/RNA

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.

Protein

 
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.

Mutations

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.
  

External links

Nomenclature
HGNC (Hugo)EHF   3246
Cards
AtlasEHFID40421ch11p13
Entrez_Gene (NCBI)EHF  26298  ets homologous factor
GeneCards (Weizmann)EHF
Ensembl (Hinxton) [Gene_View]  chr11:34642588-34684834 [Contig_View]  EHF [Vega]
cBioPortalEHF
AceView (NCBI)EHF
Genatlas (Paris)EHF
WikiGenes26298
SOURCE (Princeton)NM_001206615 NM_001206616 NM_012153
Genomic and cartography
GoldenPath (UCSC)EHF  -  11p13   chr11:34642588-34684834 +  11p12   [Description]    (hg19-Feb_2009)
EnsemblEHF - 11p12 [CytoView]
Mapping of homologs : NCBIEHF [Mapview]
OMIM605439   
Gene and transcription
Genbank (Entrez)AF124438 AF124439 AF170583 AF203977 AF212848
RefSeq transcript (Entrez)NM_001206615 NM_001206616 NM_012153
RefSeq genomic (Entrez)AC_000143 NC_000011 NC_018922 NG_029177 NT_009237 NW_001838022 NW_004929378
Consensus coding sequences : CCDS (NCBI)EHF
Cluster EST : UnigeneHs.653859 [ NCBI ]
CGAP (NCI)Hs.653859
Alternative Splicing : Fast-db (Paris)GSHG0004750
Gene ExpressionEHF [ NCBI-GEO ]     EHF [ SEEK ]   EHF [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9NZC4 (Uniprot)
NextProtQ9NZC4  [Medical]
With graphics : InterProQ9NZC4
Splice isoforms : SwissVarQ9NZC4 (Swissvar)
Domaine pattern : Prosite (Expaxy)ETS_DOMAIN_3 (PS50061)    PNT (PS51433)   
Domains : Interpro (EBI)Ets_dom [organisation]   Pointed_dom [organisation]   SAM/pointed [organisation]   WHTH_DNA-bd_dom [organisation]  
Related proteins : CluSTrQ9NZC4
Domain families : Pfam (Sanger)Ets (PF00178)    SAM_PNT (PF02198)   
Domain families : Pfam (NCBI)pfam00178    pfam02198   
Domain families : Smart (EMBL)ETS (SM00413)  SAM_PNT (SM00251)  
DMDM Disease mutations26298
Blocks (Seattle)Q9NZC4
Peptide AtlasQ9NZC4
HPRD16105
IPIIPI00172578   IPI00034048   IPI00978017   IPI00983802   IPI00979920   IPI00977813   IPI00979958   
Protein Interaction databases
DIP (DOE-UCLA)Q9NZC4
IntAct (EBI)Q9NZC4
BioGRIDEHF
InParanoidQ9NZC4
Interologous Interaction database Q9NZC4
IntegromeDBEHF
STRING (EMBL)EHF
Ontologies - Pathways
Ontology : AmiGORNA polymerase II core promoter proximal region sequence-specific DNA binding  sequence-specific DNA binding RNA polymerase II transcription factor activity  RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription  DNA binding  DNA binding  sequence-specific DNA binding transcription factor activity  nucleus  nucleus  regulation of transcription from RNA polymerase II promoter  transcription from RNA polymerase II promoter  multicellular organismal development  cell proliferation  epithelial cell differentiation  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  
Ontology : EGO-EBIRNA polymerase II core promoter proximal region sequence-specific DNA binding  sequence-specific DNA binding RNA polymerase II transcription factor activity  RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription  DNA binding  DNA binding  sequence-specific DNA binding transcription factor activity  nucleus  nucleus  regulation of transcription from RNA polymerase II promoter  transcription from RNA polymerase II promoter  multicellular organismal development  cell proliferation  epithelial cell differentiation  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  
Protein Interaction DatabaseEHF
Wikipedia pathwaysEHF
Gene fusion - rearrangments
Rearrangement : COSMICNFIA [1p31.3]  -  EHF [11p13]  
  [COSF669] [COSF670] 
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)EHF
snp3D : Map Gene to Disease26298
SNP (GeneSNP Utah)EHF
SNP : HGBaseEHF
Genetic variants : HAPMAPEHF
Exome VariantEHF
1000_GenomesEHF 
Somatic Mutations in Cancer : COSMICEHF 
CONAN: Copy Number AnalysisEHF 
Mutations and Diseases : HGMDEHF
Mutations and Diseases : intOGenEHF
Genomic VariantsEHF  EHF [DGVbeta]
dbVarEHF
ClinVarEHF
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM605439   
MedgenEHF
GENETestsEHF
Disease Genetic AssociationEHF
Huge Navigator EHF [HugePedia]  EHF [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneEHF
Homology/Alignments : Family Browser (UCSC)EHF
Phylogenetic Trees/Animal Genes : TreeFamEHF
Chemical/Protein Interactions : CTD26298
Chemical/Pharm GKB GenePA27681
Clinical trialEHF
Other databases
Probes
Litterature
PubMed40 Pubmed reference(s) in Entrez
CoreMineEHF
iHOPEHF
OncoSearchEHF

Bibliography

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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written04-2012Giuseppina M Carbone, Carlo V Catapano, Domenico Albino
Institute of Oncology Research (IOR) and Oncology Institute of Southern Switzerland (IOSI), Via Vela 6, Bellinzona, 6500 Switzerland

Citation

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 online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/EHFID40421ch11p13.html

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indexed on : Sat Oct 4 13:04:27 CEST 2014

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