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FLASH GENE
Symbol TCF3 contributors: mct/shn - updated : 22-11-2017
HGNC name transcription factor 3 (E2A immunoglobulin enhancer binding factors E12/E47)
HGNC id 11633
Corresponding disease
TCF3 pre-B cell acute lymphoblastic leukemia, LAL1, LAL pre B
Location 19p13.3      Physical location : 1.609.292 - 1.652.326
Synonym name
  • kappa-E2-binding factor
  • transcription factor E2-alpha
  • immunoglobulin enhancer-binding factor E12/E47
  • VDR interacting repressor
  • E2A immunoglobulin enhancer-binding factor E12/E47
  • immunoglobulin transcription factor 1
  • kappa-E2-binding factor
  • helix-loop-helix protein HE47
  • VDR interacting repressor
  • class B basic helix-loop-helix protein 21
  • negative vitamin D response element-binding protein
  • transcription factor ITF-1
  • vitamin D receptor-interacting repressor
  • Synonym symbol(s) E2A, ITF1, TCFE2A, EVI104, TFE2, MGC129647, E12, MGC129648, bHLHb21, VDIR, E47
    DNA
    TYPE functioning gene
    STRUCTURE 43.30 kb     19 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   transcription factor
    text structure several transcription initiation sites
    MAPPING cloned Y linked N status provisional
    Map pter - D19S886 - D19S883 - TCF3 TCF3 - D19S878 - D19S565 - cen
    Physical map
    STK11 19p13.3 serine/threonine kinase 11 (Peutz-Jeghers syndrome) MGC40084 19p13.3 hypothetical protein MGC40084 ATP5D 19p13.3 ATP synthase, H+ transporting, mitochondrial F1 complex, delta subunit MIDN 19pter-p13.3 midnolin MGC39338 19p13.3 hypothetical protein MGC39338 CIRBP 19p13.3-p13.2 cold inducible RNA binding protein FLJ20640 19p13.3 hypothetical protein FLJ20640 EFNA2 19p13.3 ephrin-A2 LOC388488 19 similar to Dip1-associated protein C MUM-1 NDUFS7 19p13 NADH dehydrogenase (ubiquinone) Fe-S protein 7, 20kDa (NADH-coenzyme Q reductase) GAMT 19p13.3 guanidinoacetate N-methyltransferase DAZAP1 19p13.3 DAZ associated protein 1 RPS15 19p13.3 ribosomal protein S15 APCL 19p13.3 ribosomal protein S15 FLJ36666 19p13.3 hypothetical protein FLJ36666 PCSK4 19p proprotein convertase subtilisin/kexin type 4 DP1L1 19p13.3 polyposis locus protein 1-like 1 LOC339366 19p13.3 hypothetical protein LOC339366 LOC126520 19p13.3 hypothetical protein LOC126520 MBD3 19p13.3 methyl-CpG binding domain protein 3 UQCR 19p13.3 ubiquinol-cytochrome c reductase (6.4kD) subunit TCF3 19p13.3 transcription factor 3 (E2A immunoglobulin enhancer binding factors E12/E47) LOC126435 19p13.3 hypothetical LOC126435 LOC390874 19 similar to onecut 3 ATP8B3 19p13.3 ATPase, Class I, type 8B, member 3 EloA-BP1 KLF16 19p13.3 Kruppel-like factor 16 MGC5244 19p13.3 hypothetical protein MGC5244 SCAMP-4 19p13.3 secretory carrier membrane protein 4 LOC113179 19p13.3 hypothetical protein BC011824
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    19 splicing 4462 67 654 - 2010 20503194
  • variant PAN-2, E12
  • specific interaction of E12 with RANBP17, a novel member of the importin-beta superfamily; this interaction maps to the CRM1 homology region of RANBP17
  • 19 splicing 4091 - 651 - 2010 20503194
  • variant PAN-1, E47
  • basic helix-loop-helix transcription factor involved in neuronal differentiation and survival
  • binds to E-box sequences within the promoter of NTRK2 and activates its transcription
  • interacts with MAP3K10, a mixed lineage kinase (MLK) involved in JNK-mediated activation of programmed cell death
  • - - 2350 - 653 - 2010 20503194
    - - 4448 - 651 - 2010 20503194
  • isoform E47, also known as Pan-1
  • EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Skin/Tegumentskin appendageshairfollicle  
     skin appendageshairsheath  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Skin/Tegumenthair follicle cell
    cell lineage ubiquitous in hematopoietic stem cell
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text embryonic tissue, in embryonic skin, expressed in basal progenitors
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a basic helix-loop-helix (BHLH) domain
  • conserved alpha-helical domains that reside within activation domains 1 and 2 (AD1 and AD2), required for interaction with CREBBP
  • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies ortholog to Tcf3, Mus musculus
    ortholog to Tcf3, Rattus norvegicus
    ortholog to tcf3, Danio rerio
    ortholog to TCF3, Pan troglodytes
    Homologene
    FAMILY
  • basic helix-loop-helix family of transcription factor
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • heterodimers between TCF3 and bHLH protein playing a major role in determining tissue-specific cell fate during embryogenesis, like muscle or early B-cell differentiation
  • potential role in renal fibrosis
  • controls proliferation and differentiation in many cell types including kidney epithelial cells
  • can also acting as a tumor suppressor gene in B-cell precursor acute lymphoblastic leukemia
  • prevent lymphoma cell expansion, at least in part through regulation of GFI1B and modulation of GATA3 expression
  • promote the developmental progression of the entire spectrum of early hematopoietic progenitors and suppress an erythroid specific program of gene expression in alternative cell lineages
  • act to promote the developmental progression of the entire spectrum of early hematopoietic progenitors
  • E protein that binds the E-box elements, and participates in CASK regulation of CDKN1A expression
  • playing a role in long-term maintenance and wound repair of both epidermis and hair follicles, suggesting that TCF proteins have both Wnt-dependent and Wnt-independent roles in lineage determination
  • key transcription factor, with TCF4, that collaborate with beta-catenin in its established role in hair follicle stem cell activation
  • with TCF4 may be essential for establishing and maintaining all skin epithelial stem cells through Wnt-dependent and Wnt-independent roles
  • basic helix-loop-helix transcription factor involved in neuronal differentiation and survival
  • SCX and TCF3 might modulate the primary chondrogenesis by associating with the SOX9-related transcriptional complex, and by binding to the conserved E-box on COL2A1 promoter
  • SNAI1, SNAI2, and TCF3 can promote collective migration during branching morphogenesis of mammary epithelial tissues through key regulators of EMT (epithelial-mesenchymal transition)
  • essential within the neural ectoderm to maintain anterior character and that its interaction with Hesx1 ensures the repression of Wnt targets in the developing forebrain
  • essential within the neural ectoderm to maintain anterior character and that its interaction with Hesx1 ensures the repression of Wnt targets in the developing forebrain
  • TCF3 and ELL2, play important roles in the regulation of B cell development in the bone marrow and differentiation of mature B cells into plasma cells in the periphery, respectively
  • essential within the neural ectoderm to maintain anterior character and interaction with HESX1 ensures the repression of Wnt targets in the developing forebrain
  • plays critical roles in inducing IgK rearrangement by directly binding to and increasing chromatin accessibility at target gene segments
  • appears to act as a “lineage-survival oncogene” for Burkitt lymphoma (BL)
  • limit expression of GATA3 to facilitate T lymphocyte lineage commitment
  • ID2/TCF3 axis orchestrates T cell differentiation through the induction or repression of downstream transcription factors essential for effector and memory T cell differentiation
  • represses Wnt-CTNNB1 signaling and maintains neural stem cell population during neocortical development
  • novel role for TCF3, an essential transcription factor regulating embryonic and adult skin stem cell functions, as a key effector of epidermal wound repair
  • role of TCF3 in cell-fate decision is more complex than previously appreciated and is highly dependent on cellular context
  • a dynamic interplay of TCF3,TCF4 transcription factors governs MYC gene expression in colo-rectal cancer
  • is an essential regulator of early B cell development
  • TCF3 together with TCF4 controlled germinal center (GC) B cell and plasma cell development
  • TCF3, TCF4 are central regulators of B cell immunity
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • heterodimer between TCF3 and BHLH
  • HAND2 formed a complex with TCF3, and bound to the E-box in the target gene promoter region
  • INTERACTION
    DNA binding cooperatively with PBXs/MEISs/PKNOX1
    RNA
    small molecule
    protein
  • Myogenin
  • ITF2
  • TAL2
  • TAL1
  • serum response factor, SRF
  • Id3
  • ABF-1
  • Ubc9
  • FB1
  • Bridge-1
  • TWIST
  • chromosome 3p kinase, 3pK and MAPKAP-K2, MK2
  • Tal1, Lmo2, Ldb1, and retinoblastoma protein
  • key direct target of TCF3 is CCND3, a regulator of the G1-S phase transition that is required for an effective germinal center reaction
  • HAND2
  • GRIPE
  • pT alpha HEB
  • CBP and PCAF
  • Daxx
  • MAP3K10
  • Asb2
  • HAND2
  • SMAD complex-associated (SCA) motif of SMAD2/3 and FOXH1
  • possible synergistic gene dosage-dependent interaction between HESX1 and TCF3, a transcriptional repressor of Wnt target genes, to maintain anterior forebrain identity
  • Id1, Id2, Id3, Id4, PRMT5, CoREST, and the chaperones of the 14-3-3 family
  • TCF3 and EP300 act in synergy to promote chromatin accessibility of the immunoglobulin &
  • 954; locus
  • YWHAG induction in Class switch DNA recombination (CSR) is enabled by the CXXC1-mediated H3K4me3 enrichment in the promoter, dependent on NFKB1 and sustained by TCF3
  • ID2 acts to repress the TCF3-mediated trans-activation of the Il10 locus
  • LCN2 is the key secreted factor downstream of TCF3 that promotes cell migration and wound healing
  • TCF3 is necessary to drive transcription of SMAD2/3 target genes, including critical regulators of dorsal cell fate and morphogenesis
  • NACC1 coordinates differentiation by activating POU5F1 and inhibiting both SOX2 and TCF3
  • TCF3 antagonism of SPI1 activity contributes likely to its ability to commit multipotential hematopoietic progenitors to the lymphoid lineages
  • BCL11B effects overlap with TCF3-dependent effects
  • cell & other
    REGULATION
    repressed by Notch (Notch regulates lymphocyte differentiation by controlling TCF3 protein turnover, ubiquitination and degradation)
    Other rgeulated by interaction with ATP1B1 in epithelial cells
    ASSOCIATED DISORDERS
    corresponding disease(s) TCF3
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    fused with HLF in t(17;19)(q22;p13) in B cell acute lymphocytic leukemia and with PBX1 in acute lymphoblastic leukemia (at postnatal time)
    tumoral   deletion    
    in acute lymphoblastic leukaemia
    tumoral     --over  
    in colorectal cancer tissue compared with normal colorectal mucosa
    tumoral       gain of function
    in glioma tissues compared with normal brain tissues, potentially promoting glioma development through the AKT1 and ERK pathways
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • homozygous Tcf3 mutant mice develop to full term without apparent abnormalities, but then display a high rate of postnatal death
  • E2A-null mutant mice fail to generate mature B cells
  • homozygous Tcf3 mutant mice show retarded postnatal growth with blocking B cell differentiation
  • mice expressing the E2A-HLF fusion gene using Ig enhancer and promoter exhibit abnormal development in the thymus and spleen and are susceptible to infection
  • Tcf3/4-null primary mouse keratinocyte cultures show a growth defect with inability to maintain long-term epidermal homeostasis