Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumours   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

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
Location 19p13.3
Location_base_pair Starts at 1560293 and ends at 1601286 bp from pter ( according to hg18-Mar_2006)  [Mapping]
Local_order not far from ENL also in 19p13.3; LYL1 is in 19p13.2-p13.1 and ELL in 19p13.1

DNA/RNA

 
  c-E2A (19p13.3) in normal cells: PAC 1116F22 - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are wellcome: contact M Rocchi
Description 17 exons; 15a and 15b alternative
Transcription 4.4kb mRNA; coding sequence: 2.0 kb; alternate splicing --> E12 and E47, having different bHLH encoding exons (+ also E2-5)

Protein

 
  c-E2A (19p13.3) in normal cells: PAC 1116F22 - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are wellcome: contact M Rocchi
Description this gene encodes E12 and E47, which are proteins which bind specifically to the immunoglobulin k chain enhancer kE2; 648-654 amino acids; 68 KDa; domains: 2 transcriptional activation domains (-> transcription factor) in the NH2-terminal, and a basic helix-loop-helix (bHLH) DNA binding site in the C-term
Expression widely expressed
Localisation nuclear
Function transcription regulation; heterodimerizes with tissue-specific bHLH proteins; homodimers are only found so far in B-lineage lymphocytes; essential for normal B-cell hematopoiesis
Homology with other proteins with a Helix-Loop-Helix dimerization domain signature, MYC type (MYC family, of which is C-MYC, LYL1, TAL1 (link))

Implicated in

Entity t(1;19)(q23;p13)/B-ALL --> hybrid gene: E2A/PBX1
Disease pre B ALL mainly; CD19+, CD10+, CD9+
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' E2A from 19p13 fused to 3' PBX1; breakpoints are clustered on both genes
Abnormal Protein N-term transcriptional activation domains from E2A fused to the Hox cooperative motif and homeodomain of C-term PBX1
Oncogenesis potent transcriptional activator; pleiotropic transforming activity
  
Entity t(17;19)(q22;p13)/B-ALL --> hybrid gene: E2A/HLF
Disease childhood B-ALL
Prognosis poor prognosis is likely
Hybrid/Mutated Gene 5' E2A - 3' HLF
Abnormal Protein N-term transcriptional activation domains from E2A fused to the basic leucine zipper from HLF C-term
Oncogenesis E2A/HLF homodimers bind to promoter/enhancer elements of downstream target genes
  

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
Entrez_Gene (NCBI)TCF3  6929  transcription factor 3 (E2A immunoglobulin enhancer binding factors E12/E47)
Cards
AtlasE2A
GeneCards (Weizmann)TCF3
Ensembl (Hinxton)ENSG00000071564 [Gene_View]  TCF3 [Vega]
AceView (NCBI)TCF3
Genatlas (Paris)TCF3
euGene (Indiana)6929
SOURCE (Stanford)NM_001136139 NM_003200
Gene Expression (Array Express) ENSG00000071564
Genomic and cartography
GoldenPath (UCSC)TCF3  -  19p13.3   chr19:1560293-1601286 -  19p13.3   [Description]    (hg18-Mar_2006)
EnsemblTCF3 - 19p13.3 [CytoView]
Mapping of homologs : NCBITCF3 [Mapview]
OMIM147141   
Gene and transcription
Gene : Genbank (Entrez)AK024806 AK310998 BC005166 BC011665 BC014680
Reference sequence (RefSeq transcript) :SRSNM_001136139 NM_003200
Reference transcript : EntrezNM_001136139 NM_003200
RefSeq genomic : SRSAC_000062 AC_000151 NC_000019 NT_011255 NW_001838476 NW_927173
RefSeq genomic : EntrezAC_000062 AC_000151 NC_000019 NT_011255 NW_001838476 NW_927173
Consensus coding sequences : CCDS NCBITCF3
Cluster EST : UnigeneHs.371282 [ SRS ] Hs.371282 [ NCBI ]
Alternative Splicing : Fast-db (Paris)1274
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtP15923 (SRS) P15923 (Expasy) P15923 (Uniprot)
With graphics : InterProP15923
Splice isoforms : VarSplice FASTAP15923(VarSplice FASTA)
Domaine pattern : Prosite (SRS)HLH (PS50888)   
Domain pattern : Prosite (Expaxy)HLH (PS50888)   
Domains : Interpro (SRS)HLH_DNA-bd_dom    HLH_DNA_bd   
Domains : Interpro (EBI)HLH_DNA-bd_dom    HLH_DNA_bd   
Related proteins : CluSTrP15923
Domain families : Pfam SRSHLH (PF00010)   
Domain families : Pfam SangerHLH (PF00010)   
Domain families : Pfam NCBIpfam00010   
Domain families : Smart EMBLHLH (SM00353)  
Blocks (Seattle)P15923
Crystal structure of protein : PDB SRS1HLH   
Crystal structure of protein : PDBSum1HLH   
Crystal structure of protein : IMB1HLH   
Crystal structure of protein : PDB RSDB1HLH   
HPRD00918
Protein Interaction databases
DIP (DOE-UCLA)P15923
IntAct (EBI)P15923
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBITCF3
SNP : GeneSNP UtahTCF3
SNP : HGBaseTCF3
Genetic variants : HAPMAPTCF3
Somatic Mutations in Cancer : COSMICTCF3 
Translocation Breakpoints in Cancer : TICdbTCF3 
Mutations and Diseases : HGMDTCF3
Hereditary diseases : OMIM147141   
Hereditary diseases : GENETests147141   
Diseases : Genetic AssociationTCF3
General knowledge
Homologs : HomoloGeneTCF3
Homology/Alignments : Family Browser UCSCTCF3
Phylogenetic Trees/Animal Genes : TreeFamTCF3
Chemical/Protein Interactions : CTD6929
Keywords Ontology : AmiGOB cell lineage commitment  transcription factor activity  transcription factor activity  nucleus  transcription activator activity  protein homodimerization activity  bHLH transcription factor binding  positive regulation of transcription from RNA polymerase II promoter  protein heterodimerization activity  protein heterodimerization activity  vitamin D response element binding  E-box binding  
Keywords Ontology : EGO-EBIB cell lineage commitment  transcription factor activity  transcription factor activity  nucleus  transcription activator activity  protein homodimerization activity  bHLH transcription factor binding  positive regulation of transcription from RNA polymerase II promoter  protein heterodimerization activity  protein heterodimerization activity  vitamin D response element binding  E-box binding  
Pathways : BIOCARTA
Pathways : KEGG
Other databases
Probes
ProbeE2A (19p13.3) in normal cells (Bari)
Probes : ImagenesTCF3 Related clones (RZPD - Berlin)
Literature
PubMed118 Pubmed reference(s) in Entrez
PubGeneTCF3

Bibliography

Chromosomal translocations involving the E2A gene in acute lymphoblastic leukemia: clinical features and molecular pathogenesis.
Hunger SP
Blood. 1996 ; 87 (4) : 1211-1224.
PMID 8608207
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

Contributor(s)

Written12-1997Jean-Loup Huret

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 .
URL : http://AtlasGeneticsOncology.org/Genes/E2A.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Sat Feb 6 13:43:44 CET 2010
Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.