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
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_basic    HLH_DNA_bd   
Domains : Interpro (EBI)HLH_basic    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  protein homodimerization activity  bHLH transcription factor binding  positive regulation of transcription, DNA-dependent  protein heterodimerization activity  
Keywords Ontology : EGO-EBIB cell lineage commitment  transcription factor activity  transcription factor activity  nucleus  protein homodimerization activity  bHLH transcription factor binding  positive regulation of transcription, DNA-dependent  protein heterodimerization activity  
Pathways : BIOCARTA
Pathways : KEGG
Other databases
Probes
ProbeE2A (19p13.3) in normal cells (Bari)
Probes : ImagenesTCF3 Related clones (RZPD - Berlin)
Literature
PubMed111 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 Jun 27 16:41:29 CEST 2009
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.