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TCF3 (transcription factor 3 (E2A immunoglobulin enhancer binding factors E12/E47))

Identity

Other namesE2A
TCF3 (Trancription Factor 3)
ITF1 Immunoglobulin Enhancer Binding
Factors E12/E47
HGNC (Hugo) TCF3
LocusID (NCBI) 6929
Location 19p13.3
Location_base_pair Starts at 1609289 and ends at 1650286 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order Proximal to ENL also in 19p13.3; LYL1 is in 19p13.2-p13.1 and ELL in 19p13.1.

DNA/RNA

 
Description The E2A gene encodes two distinct basic helix-loop-helix transcription factors, E12 (ITF1) and E47 (TCF3) through alternative splicing.
Transcription 4,4 kb mRNA; coding sequence: 2,0 kb; alternate splicing --> E12 and E47, having different bHLH encoding exons (+ also E2-5).

Protein

 
  TCF3 (19p13.3) protein and domains.
Description It forms homodimers and heterodimers with other basic helix-loop-helix transcription factors, such as ASCL1, MYOD1, TAL1, MYOG, NEUROG1, and TWIST1. It contains a transactivation domain (ADI) in N-term, a nuclear localization signal, activation domain II (ADII) (antiapoptotic), an ubiquitin ligase domain, a DNA binding motif, and a helix-loop-helix motif which mediates protein dimerisation in C-term.
Expression Widely expressed.
Localisation Nuclear.
Function Ubiquitously expressed during development and in areas of rapid cell proliferation and differentiation. Role in cell growth, cell commitment, and differentiation. Role in epithelial mesenchymal transition. During epithelial mesenchymal transition, TGF-beta upregulates E2A proteins. E2A proteins are down regulated by the ubiquitin pathway (review in Slattery et al., 2008). Essential for normal B-cell hematopoiesis.
Homology With other proteins with a helix-loop-helix dimerization domain signature, MYC type (MYC family, of which are MYC, LYL1, TAL1).

Implicated in

Entity t(1;19)(q23;p13)/B-ALL --> hybrid gene: TCF3/PBX1
Disease pre B-ALL mainly; CD19+, CD10+, CD9+ (review in Hunger, 1996).
Prognosis Controversial data; associated with poor prognostic features.
Cytogenetics Two different forms:
- the balanced t(1;19);
- the unbalanced form, with 2 normal chromosomes 1, a der(19), and a normal chromosome19: --> partial trisomy for 1q23-1qter and monosomy for 19p13.3-pter;
additional anomalies: in half of the cases; they are various.
Hybrid/Mutated Gene 5' TCF3 - 3' PBX1; breakpoints are clustered on both genes.
Abnormal Protein N-term transcriptional activation domains from TCF3 fused to the Hox cooperative motif and homeodomain of C-term PBX1.
Oncogenesis Potent transcriptional activator; pleiotropic transforming activity.
  
Entity t(12;19)(p13;p13)/B-ALL --> hybrid gene: TCF3/ZNF384
Disease Pro-B acute lymphoblastic leukemia with expression of myeloid antigens (La Starza et al., 2005; Zhong et al., 2008).
Prognosis Relatively good prognosis.
Cytogenetics The t(12;19)(p13;p13) is cryptic.
Hybrid/Mutated Gene 5' TCF3 - 3' ZNF384
  
Entity t(13;19)(q14;p13)
Disease Only one case to date, an adult patient with pre B-ALL; she achieved complete remission (Barber et al., 2007).
Hybrid/Mutated Gene The translocation involves TCF3 and an unknown partner in 13q14.
  
Entity t(17;19)(q22;p13)/B-ALL --> hybrid gene: TCF3/HLF
Disease Childhood B-ALL (Raimondi et al., 1991; Hunger et al., 1992; Inaba et al., 1992; Devaraj et al., 1994; Mathew et al., 2001; Takahashi et al., 2001; Ribeiro et al., 2002; Yeung et al., 2006; Barber et al., 2007).
Prognosis Poor prognosis is likely.
Hybrid/Mutated Gene 5' TCF3 - 3' HLF
Abnormal Protein N-term transcriptional activation domains from TCF3 fused to the basic leucine zipper from HLF C-term.
Oncogenesis TCF3/HLF homodimers bind to promoter/enhancer elements of downstream target genes.
  
Entity t(19;19)(p13;q13)/B-ALL --> hybrid gene: TCF3/TFPT
Disease Childhood pre-B cell acute lymphoblastic leukemia (Brambillasca et al., 1999).
Cytogenetics This chromosome rearrangement is cryptic.
Hybrid/Mutated Gene 5' TCF3 - 3' TFPT
Abnormal Protein Retains the transactivation domain of TCF3, but with a truncation in TFPT, due to the frequent occurrence of a stop codon.
  

Breakpoints

 
 
Note Breakpoints: 1- in t(1;19): are located (and dispersed) in the intron 13, and remove the bHLH domain; 2- in t(17;19) type I: are so far located at a given nucleotide in intron 13; in t(17;19) type II: are located in intron 12.

External links

Nomenclature
HGNC (Hugo)TCF3   11633
Cards
AtlasE2A
Entrez_Gene (NCBI)TCF3  6929  transcription factor 3
GeneCards (Weizmann)TCF3
Ensembl (Hinxton)ENSG00000071564 [Gene_View]  chr19:1609289-1650286 [Contig_View]  TCF3 [Vega]
AceView (NCBI)TCF3
Genatlas (Paris)TCF3
WikiGenes6929
SOURCE (Princeton)NM_001136139 NM_003200
Genomic and cartography
GoldenPath (UCSC)TCF3  -  19p13.3   chr19:1609289-1650286 -  19p13.3   [Description]    (hg19-Feb_2009)
EnsemblTCF3 - 19p13.3 [CytoView]
Mapping of homologs : NCBITCF3 [Mapview]
OMIM147141   
Gene and transcription
Genbank (Entrez)AK024806 AK310998 AW028755 BC005166 BC011665
RefSeq transcript (Entrez)NM_001136139 NM_003200
RefSeq genomic (Entrez)AC_000151 NC_000019 NC_018930 NG_029953 NT_011255 NW_001838476 NW_004929412
Consensus coding sequences : CCDS (NCBI)TCF3
Cluster EST : UnigeneHs.657044 [ NCBI ]
CGAP (NCI)Hs.657044
Alternative Splicing : Fast-db (Paris)GSHG0015323
Alternative Splicing GalleryENSG00000071564
Gene ExpressionTCF3 [ NCBI-GEO ]     TCF3 [ SEEK ]   TCF3 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP15923 (Uniprot)
NextProtP15923  [Medical]
With graphics : InterProP15923
Splice isoforms : SwissVarP15923 (Swissvar)
Domaine pattern : Prosite (Expaxy)BHLH (PS50888)   
Domains : Interpro (EBI)bHLH_dom   
Related proteins : CluSTrP15923
Domain families : Pfam (Sanger)HLH (PF00010)   
Domain families : Pfam (NCBI)pfam00010   
Domain families : Smart (EMBL)HLH (SM00353)  
DMDM Disease mutations6929
Blocks (Seattle)P15923
PDB (SRS)1HLH    3U5V   
PDB (PDBSum)1HLH    3U5V   
PDB (IMB)1HLH    3U5V   
PDB (RSDB)1HLH    3U5V   
Human Protein AtlasENSG00000071564
Peptide AtlasP15923
HPRD00918
IPIIPI00013929   IPI00216911   IPI01013804   IPI00719590   
Protein Interaction databases
DIP (DOE-UCLA)P15923
IntAct (EBI)P15923
FunCoupENSG00000071564
BioGRIDTCF3
InParanoidP15923
Interologous Interaction database P15923
IntegromeDBTCF3
STRING (EMBL)TCF3
Ontologies - Pathways
Ontology : AmiGOnuclear nucleosome  natural killer cell differentiation  B cell lineage commitment  B cell lineage commitment  DNA binding  DNA binding  DNA binding  chromatin binding  sequence-specific DNA binding transcription factor activity  sequence-specific DNA binding transcription factor activity  transcription coactivator activity  protein binding  nucleus  nucleus  nucleoplasm  transcription factor complex  cytoplasm  transcription, DNA-templated  regulation of transcription, DNA-dependent  transcription factor binding  B cell differentiation  positive regulation of B cell proliferation  mitogen-activated protein kinase kinase kinase binding  response to lipopolysaccharide  T cell differentiation in thymus  immunoglobulin V(D)J recombination  response to drug  muscle cell differentiation  protein homodimerization activity  protein complex  bHLH transcription factor binding  sequence-specific DNA binding  sequence-specific DNA binding  histone H3 acetylation  histone H4 acetylation  transcription regulatory region DNA binding  positive regulation of neuron differentiation  positive regulation of cell cycle  positive regulation of transcription, DNA-dependent  positive regulation of transcription, DNA-dependent  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  protein heterodimerization activity  protein heterodimerization activity  protein heterodimerization activity  cell development  Peyer's patch development  protein stabilization  positive regulation of sequence-specific DNA binding transcription factor activity  positive regulation of muscle cell differentiation  repressing transcription factor binding  vitamin D response element binding  E-box binding  E-box binding  E-box binding  regulation of G1/S transition of mitotic cell cycle  
Ontology : EGO-EBInuclear nucleosome  natural killer cell differentiation  B cell lineage commitment  B cell lineage commitment  DNA binding  DNA binding  DNA binding  chromatin binding  sequence-specific DNA binding transcription factor activity  sequence-specific DNA binding transcription factor activity  transcription coactivator activity  protein binding  nucleus  nucleus  nucleoplasm  transcription factor complex  cytoplasm  transcription, DNA-templated  regulation of transcription, DNA-dependent  transcription factor binding  B cell differentiation  positive regulation of B cell proliferation  mitogen-activated protein kinase kinase kinase binding  response to lipopolysaccharide  T cell differentiation in thymus  immunoglobulin V(D)J recombination  response to drug  muscle cell differentiation  protein homodimerization activity  protein complex  bHLH transcription factor binding  sequence-specific DNA binding  sequence-specific DNA binding  histone H3 acetylation  histone H4 acetylation  transcription regulatory region DNA binding  positive regulation of neuron differentiation  positive regulation of cell cycle  positive regulation of transcription, DNA-dependent  positive regulation of transcription, DNA-dependent  positive regulation of transcription from RNA polymerase II promoter  positive regulation of transcription from RNA polymerase II promoter  protein heterodimerization activity  protein heterodimerization activity  protein heterodimerization activity  cell development  Peyer's patch development  protein stabilization  positive regulation of sequence-specific DNA binding transcription factor activity  positive regulation of muscle cell differentiation  repressing transcription factor binding  vitamin D response element binding  E-box binding  E-box binding  E-box binding  regulation of G1/S transition of mitotic cell cycle  
Pathways : KEGGHTLV-I infection    Transcriptional misregulation in cancer   
REACTOMETCF3
Protein Interaction DatabaseTCF3
Wikipedia pathwaysTCF3
Gene fusion - rearrangments
Rearrangement : TICdbHLF [17q22]  -  TCF3 [19p13.3]
Rearrangement : TICdbNOP2 [12p13.31]  -  TCF3 [19p13.3]
Rearrangement : TICdbPBX1 [1q23.3]  -  TCF3 [19p13.3]
Rearrangement : TICdbTCF3 [19p13.3]  -  HLF [17q22]
Rearrangement : TICdbTCF3 [19p13.3]  -  NOP2 [12p13.31]
Rearrangement : TICdbTCF3 [19p13.3]  -  PBX1 [1q23.3]
Rearrangement : TICdbTCF3 [19p13.3]  -  TCF3 [19p13.3]
Rearrangement : TICdbTCF3 [19p13.3]  -  TCF3 [19p13.3]
Rearrangement : TICdbTCF3 [19p13.3]  -  TFPT [19q13.42]
Rearrangement : TICdbTCF3 [19p13.3]  -  ZNF384 [12p13.31]
Rearrangement : TICdbTFPT [19q13.42]  -  TCF3 [19p13.3]
Rearrangement : TICdbZNF384 [12p13.31]  -  TCF3 [19p13.3]
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)TCF3
SNP (GeneSNP Utah)TCF3
SNP : HGBaseTCF3
Genetic variants : HAPMAPTCF3
1000_GenomesTCF3 
ICGC programENSG00000071564 
Cancer Gene: CensusTCF3 
Somatic Mutations in Cancer : COSMICTCF3 
CONAN: Copy Number AnalysisTCF3 
Mutations and Diseases : HGMDTCF3
OMIM147141   
GENETestsTCF3
Disease Genetic AssociationTCF3
Huge Navigator TCF3 [HugePedia]  TCF3 [HugeCancerGEM]
Genomic VariantsTCF3  TCF3 [DGVbeta]
Exome VariantTCF3
dbVarTCF3
ClinVarTCF3
snp3D : Map Gene to Disease6929
General knowledge
Homologs : HomoloGeneTCF3
Homology/Alignments : Family Browser (UCSC)TCF3
Phylogenetic Trees/Animal Genes : TreeFamTCF3
Chemical/Protein Interactions : CTD6929
Chemical/Pharm GKB GenePA164742580
Clinical trialTCF3
Cancer Resource (Charite)ENSG00000071564
Other databases
Probes
Litterature
PubMed183 Pubmed reference(s) in Entrez
CoreMineTCF3
iHOPTCF3

Bibliography

New recurring chromosomal translocations in childhood acute lymphoblastic leukemia.
Raimondi SC, Privitera E, Williams DL, Look AT, Behm F, Rivera GK, Crist WM, Pui CH.
Blood. 1991 May 1;77(9):2016-22.
PMID 2018838
 
Hlf, a novel hepatic bZIP protein, shows altered DNA-binding properties following fusion to E2A in t(17;19) acute lymphoblastic leukemia.
Hunger SP, Ohyashiki K, Toyama K, Cleary ML.
Genes Dev. 1992 Sep;6(9):1608-20.
PMID 1516826
 
Fusion of the leucine zipper gene HLF to the E2A gene in human acute B-lineage leukemia.
Inaba T, Roberts WM, Shapiro LH, Jolly KW, Raimondi SC, Smith SD, Look AT.
Science. 1992 Jul 24;257(5069):531-4.
PMID 1386162
 
E2A/HLF fusion cDNAs and the use of RT-PCR for the detection of minimal residual disease in t(17;19)(q22;p13) acute lymphoblastic leukemia.
Devaraj PE, Foroni L, Sekhar M, Butler T, Wright F, Mehta A, Samson D, Prentice HG, Hoffbrand AV, Secker-Walker LM.
Leukemia. 1994 Jul;8(7):1131-8.
PMID 7518549
 
Hairy cell leukemia is characterized by clonal chromosome abnormalities clustered to specific regions.
Haglund U, Juliusson G, Stellan B, Gahrton G.
Blood. 1994 May 1;83(9):2637-45.
PMID 8167343
 
Chromosomal translocations involving the E2A gene in acute lymphoblastic leukemia: clinical features and molecular pathogenesis.
Hunger SP.
Blood. 1996 Feb 15;87(4):1211-24.
PMID 8608207
 
The AD1 and AD2 transactivation domains of E2A are essential for the antiapoptotic activity of the chimeric oncoprotein E2A-HLF.
Inukai T, Inaba T, Ikushima S, Look AT.
Mol Cell Biol. 1998 Oct;18(10):6035-43.
PMID 9742120
 
Identification of a novel molecular partner of the E2A gene in childhood leukemia.
Brambillasca F, Mosna G, Colombo M, Rivolta A, Caslini C, Minuzzo M, Giudici G, Mizzi L, Biondi A, Privitera E.
Leukemia. 1999 Mar;13(3):369-75.
PMID 10086727
 
Multicolor spectral karyotyping identifies novel translocations in childhood acute lymphoblastic leukemia.
Mathew S, Rao PH, Dalton J, Downing JR, Raimondi SC.
Leukemia. 2001 Mar;15(3):468-72.
PMID 11237073
 
Expression of two types of E2A-HLF fusion proteins in YCUB-2, a novel cell line established from B-lineage leukemia with t(17;19).
Takahashi H, Goto H, Eunabiki T, Fujii H, Yamazaki S, Fujioka K, Ikuta K, Kai S.
Leukemia. 2001 Jun;15(6):995-7.
PMID 11417493
 
Microsatellite instability and cytogenetic survey in myeloid leukemias.
Ribeiro EM, Rodriguez JM, Coser VM, Sotero MG, Fonseca Neto JM, Pasquini R, Cavalli IJ.
Braz J Med Biol Res. 2002 Feb;35(2):153-9.
PMID 11847518
 
CIZ gene rearrangements in acute leukemia: report of a diagnostic FISH assay and clinical features of nine patients.
La Starza R, Aventin A, Crescenzi B, Gorello P, Specchia G, Cuneo A, Angioni A, Bilhou-Nabera C, Boque C, Foa R, Uyttebroeck A, Talmant P, Cimino G, Martelli MF, Marynen P, Mecucci C, Hagemeijer A.
Leukemia. 2005 Sep;19(9):1696-9.
PMID 15990865
 
Characterization of the t(17;19) translocation by gene-specific fluorescent in situ hybridization-based cytogenetics and detection of the E2A-HLF fusion transcript and protein in patients' cells.
Yeung J, Kempski H, Neat M, Bailey S, Smith O, Brady HJ.
Haematologica. 2006 Mar;91(3):422-4.
PMID 16531271
 
Molecular cytogenetic characterization of TCF3 (E2A)/19p13.3 rearrangements in B-cell precursor acute lymphoblastic leukemia.
Barber KE, Harrison CJ, Broadfield ZJ, Stewart AR, Wright SL, Martineau M, Strefford JC, Moorman AV.
Genes Chromosomes Cancer. 2007 May;46(5):478-86.
PMID 17311319
 
E2A proteins: regulators of cell phenotype in normal physiology and disease.
Slattery C, Ryan MP, McMorrow T.
Int J Biochem Cell Biol. 2008;40(8):1431-6. Epub 2007 May 29. (REVIEW)
PMID 17604208
 
E2A-ZNF384 and NOL1-E2A fusion created by a cryptic t(12;19)(p13.3; p13.3) in acute leukemia.
Zhong CH, Prima V, Liang X, Frye C, McGavran L, Meltesen L, Wei Q, Boomer T, Varella-Garcia M, Gump J, Hunger SP.
Leukemia. 2008 Apr;22(4):723-9. Epub 2008 Jan 10.
PMID 18185522
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written12-1997Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Updated01-2012Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Citation

This paper should be referenced as such :
Huret JL . TCF3 (transcription factor 3 (E2A immunoglobulin enhancer binding factors E12/E47)). Atlas Genet Cytogenet Oncol Haematol. December 1997 .
Huret JL . TCF3 (transcription factor 3 (E2A immunoglobulin enhancer binding factors E12/E47)). Atlas Genet Cytogenet Oncol Haematol. January 2012 .
URL : http://AtlasGeneticsOncology.org/Genes/E2A.html

The various updated versions of this paper are referenced and archived by INIST as such :
http://documents.irevues.inist.fr/bitstream/handle/2042/32052/10-1997-E2A.pdf   [ Bibliographic record ]
http://documents.irevues.inist.fr/bitstream/handle/2042/47341/01-2012-E2A.pdf   [ Bibliographic record ]

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indexed on : Fri Apr 18 17:37:10 CEST 2014

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