TCF3

Protein-coding gene in the species Homo sapiens
TCF3
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

2MH0, 2YPA, 2YPB, 3U5V

Identifiers
AliasesTCF3, E2A, E47, ITF1, TCF-3, VDIR, bHLHb21, AGM8, transcription factor 3, p75
External IDsOMIM: 147141 MGI: 98510 HomoloGene: 2408 GeneCards: TCF3
Gene location (Human)
Chromosome 19 (human)
Chr.Chromosome 19 (human)[1]
Chromosome 19 (human)
Genomic location for TCF3
Genomic location for TCF3
Band19p13.3Start1,609,290 bp[1]
End1,652,605 bp[1]
Gene location (Mouse)
Chromosome 10 (mouse)
Chr.Chromosome 10 (mouse)[2]
Chromosome 10 (mouse)
Genomic location for TCF3
Genomic location for TCF3
Band10 C1|10 39.72 cMStart80,245,348 bp[2]
End80,269,481 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • ganglionic eminence

  • pancreatic ductal cell

  • lymph node

  • bone marrow cells

  • appendix

  • stromal cell of endometrium

  • spleen

  • trabecular bone

  • parotid gland

  • blood
Top expressed in
  • maxillary prominence

  • lip

  • somite

  • abdominal wall

  • yolk sac

  • internal carotid artery

  • renal corpuscle

  • thymus

  • external carotid artery

  • medullary collecting duct
More reference expression data
BioGPS




More reference expression data
Gene ontology
Molecular function
  • DNA binding
  • sequence-specific DNA binding
  • protein dimerization activity
  • protein homodimerization activity
  • DNA-binding transcription factor activity
  • mitogen-activated protein kinase kinase kinase binding
  • vitamin D response element binding
  • transcription coactivator activity
  • transcription factor binding
  • RNA polymerase II cis-regulatory region sequence-specific DNA binding
  • DNA-binding transcription repressor activity, RNA polymerase II-specific
  • bHLH transcription factor binding
  • E-box binding
  • protein binding
  • protein heterodimerization activity
  • DNA-binding transcription factor activity, RNA polymerase II-specific
Cellular component
  • cytoplasm
  • transcription regulator complex
  • RNA polymerase II transcription regulator complex
  • nucleus
  • nuclear speck
  • nucleoplasm
  • protein-containing complex
Biological process
  • cell differentiation
  • regulation of transcription, DNA-templated
  • positive regulation of muscle cell differentiation
  • positive regulation of DNA-binding transcription factor activity
  • negative regulation of transcription by RNA polymerase II
  • transcription, DNA-templated
  • nervous system development
  • positive regulation of transcription, DNA-templated
  • regulation of G1/S transition of mitotic cell cycle
  • B cell lineage commitment
  • positive regulation of cell cycle
  • positive regulation of B cell proliferation
  • positive regulation of neuron differentiation
  • B cell differentiation
  • immunoglobulin V(D)J recombination
  • positive regulation of transcription by RNA polymerase II
  • regulation of hematopoietic stem cell differentiation
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

6929

21423

Ensembl

ENSG00000071564

ENSMUSG00000020167

UniProt

P15923

P15806

RefSeq (mRNA)

NM_001136139
NM_003200
NM_001351778
NM_001351779

NM_001164147
NM_001164148
NM_001164149
NM_001164150
NM_001164151

NM_001164152
NM_001164153
NM_011548
NM_001378903
NM_001378904
NM_001378905
NM_001378908
NM_001378910
NM_001378912
NM_001378913
NM_001378914

RefSeq (protein)

NP_001129611
NP_003191
NP_001338707
NP_001338708

NP_001157619
NP_001157620
NP_001157621
NP_001157622
NP_001157623

NP_001157624
NP_001157625
NP_035678
NP_001365832
NP_001365833
NP_001365834
NP_001365837
NP_001365839
NP_001365841
NP_001365842
NP_001365843

Location (UCSC)Chr 19: 1.61 – 1.65 MbChr 10: 80.25 – 80.27 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Transcription factor 3 (E2A immunoglobulin enhancer-binding factors E12/E47), also known as TCF3, is a protein that in humans is encoded by the TCF3 gene.[5][6][7] TCF3 has been shown to directly enhance Hes1 (a well-known target of Notch signaling) expression.[8]

Function

This gene encodes a member of the E protein (class I) family of helix-loop-helix transcription factors. The 9aaTAD transactivation domains of E proteins and MLL are very similar and both bind to the KIX domain of general transcriptional mediator CBP.[9][10] E proteins activate transcription by binding to regulatory E-box sequences on target genes as heterodimers or homodimers, and are inhibited by heterodimerization with inhibitor of DNA-binding (class IV) helix-loop-helix proteins. E proteins play a critical role in lymphopoiesis, and the encoded protein is required for the B and T lymphocyte development.[5]

9aaTADs in the E protein family E2A and MLL binding to the KIX domain of CBP

This gene regulates many developmental patterning processes such as lymphocyte and central nervous system (CNS) development. E proteins are involved in the development of lymphocytes.[11] They initiate transcription by binding to regulatory E-box sequences on target genes.

Clinical significance

Deletion of this gene or diminished activity of the encoded protein may play a role in lymphoid malignancies. This gene is also involved in several chromosomal translocations that are associated with lymphoid malignancies including pre-B-cell acute lymphoblastic leukemia (t(1;19), with PBX1 and t(17;19), with HLF),[12] childhood leukemia (t(19;19), with TFPT) and acute leukemia (t(12;19), with ZNF384).[5]

Interactions

TCF3 has been shown to interact with:

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000071564 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020167 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b c "Entrez Gene: TCF3".
  6. ^ Henthorn P, McCarrick-Walmsley R, Kadesch T (Feb 1990). "Sequence of the cDNA encoding ITF-1, a positive-acting transcription factor". Nucleic Acids Research. 18 (3): 677. doi:10.1093/nar/18.3.677. PMC 333499. PMID 2308859.
  7. ^ Kamps MP, Murre C, Sun XH, Baltimore D (Feb 1990). "A new homeobox gene contributes the DNA binding domain of the t(1;19) translocation protein in pre-B ALL". Cell. 60 (4): 547–55. doi:10.1016/0092-8674(90)90658-2. PMID 1967983. S2CID 39661371.
  8. ^ E proteins and Notch signaling cooperate to promote T cell lineage specification and commitment
  9. ^ Piskacek, S (2007). "Nine-amino-acid transactivation domain: Establishment and prediction utilities". Genomics. 89 (6): 756–768. doi:10.1016/j.ygeno.2007.02.003. PMID 17467953.
  10. ^ Piskacek, Martin; Vasku, A; Hajek, R; Knight, A (2015). "Shared structural features of the 9aaTAD family in complex with CBP". Mol. Biosyst. 11 (3): 844–851. doi:10.1039/c4mb00672k. PMID 25564305.
  11. ^ Quong MW, Romanow WJ, Murre C (2002). "E protein function in lymphocyte development". Annual Review of Immunology. 20: 301–22. doi:10.1146/annurev.immunol.20.092501.162048. PMID 11861605.
  12. ^ Herblot, Sabine; Aplan, Peter D.; Hoang, Trang (2002-02-01). "Gradient of E2A Activity in B-Cell Development". Molecular and Cellular Biology. 22 (3): 886–900. doi:10.1128/MCB.22.3.886-900.2002. ISSN 0270-7306. PMC 133542. PMID 11784864.
  13. ^ a b c Goardon N, Lambert JA, Rodriguez P, Nissaire P, Herblot S, Thibault P, Dumenil D, Strouboulis J, Romeo PH, Hoang T (Jan 2006). "ETO2 coordinates cellular proliferation and differentiation during erythropoiesis". The EMBO Journal. 25 (2): 357–66. doi:10.1038/sj.emboj.7600934. PMC 1383517. PMID 16407974.
  14. ^ a b c Bradney C, Hjelmeland M, Komatsu Y, Yoshida M, Yao TP, Zhuang Y (Jan 2003). "Regulation of E2A activities by histone acetyltransferases in B lymphocyte development". The Journal of Biological Chemistry. 278 (4): 2370–6. doi:10.1074/jbc.M211464200. PMID 12435739.
  15. ^ Maira SM, Wurtz JM, Wasylyk B (Nov 1996). "Net (ERP/SAP2) one of the Ras-inducible TCFs, has a novel inhibitory domain with resemblance to the helix-loop-helix motif". The EMBO Journal. 15 (21): 5849–65. doi:10.1002/j.1460-2075.1996.tb00972.x. PMC 452333. PMID 8918463.
  16. ^ Deed RW, Jasiok M, Norton JD (Apr 1998). "Lymphoid-specific expression of the Id3 gene in hematopoietic cells. Selective antagonism of E2A basic helix-loop-helix protein associated with Id3-induced differentiation of erythroleukemia cells". The Journal of Biological Chemistry. 273 (14): 8278–86. doi:10.1074/jbc.273.14.8278. PMID 9525934.
  17. ^ a b c Langlands K, Yin X, Anand G, Prochownik EV (Aug 1997). "Differential interactions of Id proteins with basic-helix-loop-helix transcription factors". The Journal of Biological Chemistry. 272 (32): 19785–93. doi:10.1074/jbc.272.32.19785. PMID 9242638.
  18. ^ Johnson JD, Zhang W, Rudnick A, Rutter WJ, German MS (Jul 1997). "Transcriptional synergy between LIM-homeodomain proteins and basic helix-loop-helix proteins: the LIM2 domain determines specificity". Molecular and Cellular Biology. 17 (7): 3488–96. doi:10.1128/mcb.17.7.3488. PMC 232202. PMID 9199284.
  19. ^ Miyamoto A, Cui X, Naumovski L, Cleary ML (May 1996). "Helix-loop-helix proteins LYL1 and E2a form heterodimeric complexes with distinctive DNA-binding properties in hematolymphoid cells". Molecular and Cellular Biology. 16 (5): 2394–401. doi:10.1128/mcb.16.5.2394. PMC 231228. PMID 8628307.
  20. ^ Neufeld B, Grosse-Wilde A, Hoffmeyer A, Jordan BW, Chen P, Dinev D, Ludwig S, Rapp UR (Jul 2000). "Serine/Threonine kinases 3pK and MAPK-activated protein kinase 2 interact with the basic helix-loop-helix transcription factor E47 and repress its transcriptional activity". The Journal of Biological Chemistry. 275 (27): 20239–42. doi:10.1074/jbc.C901040199. PMID 10781029.
  21. ^ Maleki SJ, Royer CA, Hurlburt BK (Jun 1997). "MyoD-E12 heterodimers and MyoD-MyoD homodimers are equally stable". Biochemistry. 36 (22): 6762–7. doi:10.1021/bi970262m. PMID 9184158.
  22. ^ Chakraborty T, Martin JF, Olson EN (Sep 1992). "Analysis of the oligomerization of myogenin and E2A products in vivo using a two-hybrid assay system". The Journal of Biological Chemistry. 267 (25): 17498–501. doi:10.1016/S0021-9258(19)37069-3. PMID 1325437.
  23. ^ Hsu HL, Wadman I, Baer R (Apr 1994). "Formation of in vivo complexes between the TAL1 and E2A polypeptides of leukemic T cells". Proceedings of the National Academy of Sciences of the United States of America. 91 (8): 3181–5. Bibcode:1994PNAS...91.3181H. doi:10.1073/pnas.91.8.3181. PMC 43539. PMID 8159721.
  24. ^ El Ghouzzi V, Legeai-Mallet L, Aresta S, Benoist C, Munnich A, de Gunzburg J, Bonaventure J (Mar 2000). "Saethre-Chotzen mutations cause TWIST protein degradation or impaired nuclear location". Human Molecular Genetics. 9 (5): 813–9. doi:10.1093/hmg/9.5.813. PMID 10749989.
  25. ^ Huggins GS, Chin MT, Sibinga NE, Lee SL, Haber E, Lee ME (Oct 1999). "Characterization of the mUBC9-binding sites required for E2A protein degradation". The Journal of Biological Chemistry. 274 (40): 28690–6. doi:10.1074/jbc.274.40.28690. PMID 10497239.

Further reading

  • LeBrun DP (May 2003). "E2A basic helix-loop-helix transcription factors in human leukemia". Frontiers in Bioscience. 8 (1–3): s206–22. doi:10.2741/1030. PMID 12700034.
  • v
  • t
  • e
(1) Basic domains
(1.1) Basic leucine zipper (bZIP)
(1.2) Basic helix-loop-helix (bHLH)
Group A
Group B
Group C
bHLH-PAS
Group D
Group E
Group F
bHLH-COE
(1.3) bHLH-ZIP
(1.4) NF-1
(1.5) RF-X
(1.6) Basic helix-span-helix (bHSH)
(2) Zinc finger DNA-binding domains
(2.1) Nuclear receptor (Cys4)
subfamily 1
subfamily 2
subfamily 3
subfamily 4
subfamily 5
subfamily 6
subfamily 0
(2.2) Other Cys4
(2.3) Cys2His2
(2.4) Cys6
(2.5) Alternating composition
(2.6) WRKY
(3) Helix-turn-helix domains
(3.1) Homeodomain
Antennapedia
ANTP class
protoHOX
Hox-like
metaHOX
NK-like
other
(3.2) Paired box
(3.3) Fork head / winged helix
(3.4) Heat shock factors
(3.5) Tryptophan clusters
(3.6) TEA domain
  • transcriptional enhancer factor
(4) β-Scaffold factors with minor groove contacts
(4.1) Rel homology region
(4.2) STAT
(4.3) p53-like
(4.4) MADS box
(4.6) TATA-binding proteins
(4.7) High-mobility group
(4.9) Grainyhead
(4.10) Cold-shock domain
(4.11) Runt
(0) Other transcription factors
(0.2) HMGI(Y)
(0.3) Pocket domain
(0.5) AP-2/EREBP-related factors
(0.6) Miscellaneous
see also transcription factor/coregulator deficiencies

This article incorporates text from the United States National Library of Medicine, which is in the public domain.