AC T00204
XX
ID T00204
XX
DT 15.10.1992 (created); ewi.
DT 22.07.2010 (updated); mku.
CO Copyright (C), QIAGEN.
XX
FA E12
XX
SY E12; E2-alpha; E2A; E2A-E12; E2A.E12; TCF3.
XX
OS human, Homo sapiens
OC eukaryota; animalia; metazoa; chordata; vertebrata; tetrapoda; mammalia; eutheria; primates
XX
GE G003922 TCF3; HGNC: TCF3.
XX
CL C0010; bHLH; 1.2.1.0.1.1.
XX
SZ 654 AA; 67.6 kDa (cDNA) (calc.).
XX
SQ MNQPQRMAPVGTDKELSDLLDFSMMFPLPVTNGKGRPASLAGAQFGGSGLEDRPSSGSWG
SQ SGDQSSSSFDPSRTFSEGTHFTESHSSLSSSTFLGPGLGGKSGERGAYASFGRDAGVGGL
SQ TQAGFLSGELALNSPGPLSPSGMKGTSQYYPSYSGSSRRRAADGSLDTQPKKVRKVPPGL
SQ PSSVYPPSSGEDYGRDATAYPSAKTPSSTYPAPFYVADGSLHPSAELWSPPGQAGFGPML
SQ GGGSSPLPLPPGSGPVGSSGSSSTFGGLHQHERMGYQLHGAEVNGGLPSASSFSSAPGAT
SQ YGGVSSHTPPVSGADSLLGSRGTTAGSSGDALGKALASIYSPDHSSNNFSSSPSTPVGSP
SQ QGLAGTSQWPRAGAPGALSPSYDGGLHGLQSKIEDHLDEAIHVLRSHAVGTAGDMHTLLP
SQ GHGALASGFTGPMSLGGRHAGLVGGSHPEDGLAGSTSLMHNHAALPSQPGTLPDLSRPPD
SQ SYSGLGRAGATAAASEIKREEKEDEENTSAADHSEEEKKELKAPRARTSPDEDEDDLLPP
SQ EQKAEREKERRVANNARERLRVRDINEAFKELGRMCQLHLNSEKPQTKLLILHQAVSVIL
SQ NLEQQVRERNLNPKAACLKRREEEKVSGVVGDPQMVLSAPHPGLSEAHNPAGHM
XX
SC Swiss-Prot#P15923-1
XX
FT 1 83 
trans-activation domain [19].
FT 348 406 
trans-activation domain [19].
FT 547 603 
PS50888; HLH.
FT 550 603 
PF00010; Helix-loop-helix DNA-binding domain.
FT 555 608 
SM00353; finulus.
FT 576 576 
cysteine involved in disulfide-linkage between homodimer constituents [26].
XX
SF class A specific domain [5];
SF putative leucine zipper motif (L2TL2) may be N-terminally extended due to the lack of Q390 which brings an additional L in phase [3];
SF spontaneous homodimerization in B cells, stabilized by disulfide links [26];
SF reducing activity in muscle cells provides monomers that preferentially heterodimerize with, e. g., MyoD [26];
SF dimerization specificity with MyoD is defined by several hydrogen bonds and charged pairs [16];
SF heterodimerizes with myogenin [30];
SF trans-activation domain may comprise a novel loop-helix motif [19];
SF the trans-activating domain at 348-406 is targeted by the bZIP domain of c-Jun when repressing the activation potential of E2A proteins [28];
XX
CP ubiquitous.
XX
FF activator [19];
FF poorly DNA-binding as homodimer due to an inhibitory N-terminal domain, but avid DNA-binding in any heterodimeric complex [1] [5];
FF the inhibitory region also defines different DNA-binding specificities between E12 and E47 [5] [13];
FF may be involved in tissue-specific gene regulation of muscle, lymphoid, or neural cells when heterodimerizing with cell-specific components;
FF growth-inhibitory activity [25];
FF despite functional redundancy with other related factors (E2A or E2-2 gene products), only E12/E47 are found in mature B cells [18];
FF in acute lymphoblastic leukemias, a t(1,19)(q23,p13.3) translocation fuses the trans-activation domain encoded by the E2A gene with the homeobox of PBX1 [21] [4] [8];
FF E2A-PBX1 chimeric protein causes acute myeloid leukemia [23];
FF E2A-PBX1 chimeric protein induces enhanced proliferation as well as apoptosis [27];
XX
IN T00036 AP-4; human, Homo sapiens.
IN T00003 AS-C T3; fruit fly, Drosophila melanogaster.
IN T01621 ASH-1; clawed frog, Xenopus laevis.
IN T01653 Delilah; fruit fly, Drosophila melanogaster.
IN T02404 Dermo-1; mouse, Mus musculus.
IN T00204 E12; human, Homo sapiens.
IN T00207 E47; human, Homo sapiens.
IN T00674 E47; rat, Rattus norvegicus.
IN T01788 E47; mouse, Mus musculus.
IN T01569 EHAND; mouse, Mus musculus.
IN T01447 HEN1; rat, Rattus norvegicus.
IN T01503 HTF4; human, Homo sapiens.
IN T00403 Id1; mouse, Mus musculus.
IN T00404 Id2; mouse, Mus musculus.
IN T01212 Id2; human, Homo sapiens.
IN T10004 Id2; mouse, Mus musculus.
IN T09198 Id3; mouse, Mus musculus.
IN T01794 INSAF; human, Homo sapiens.
IN T10018 Lyl-1; human, Homo sapiens.
IN T00484 MASH-1; rat, Rattus norvegicus.
IN T01619 MASH-1; mouse, Mus musculus.
IN T01620 MASH-1; human, Homo sapiens.
IN T00485 MASH-2; rat, Rattus norvegicus.
IN T00512 MRF4; rat, Rattus norvegicus.
IN T00521 Myf-5; human, Homo sapiens.
IN T00949 Myf-5; clawed frog, Xenopus laevis.
IN T00522 Myf-6; human, Homo sapiens.
IN T00524 MyoD; clawed frog, Xenopus laevis.
IN T00525 MyoD; human, Homo sapiens.
IN T00526 MyoD; mouse, Mus musculus.
IN T00527 MyoD; monkey, Cercopithecus aethiops.
IN T01128 MyoD; chick, Gallus gallus.
IN T09177 MyoD; mouse, Mus musculus.
IN T10010 MyoD; clawed frog, Xenopus laevis.
IN T00520 Myogenin; human, Homo sapiens.
IN T00528 myogenin; mouse, Mus musculus.
IN T10831 Myogenin; Mammalia.
IN T01634 NeuroD; hamster, Cricetulus sp.
IN T19232 scx; mouse, Mus musculus.
IN T00926 SUM-1; sea urchin, Lytechinus variegatus.
IN T01631 Tal-2; mouse, Mus musculus.
IN T00790 Tal1-PP42; human, Homo sapiens.
IN T09977 TWIST; human, Homo sapiens.
XX
MX M00693 V$E12_Q6.
MX M00804 V$E2A_Q2.
MX M00973 V$E2A_Q6.
MX M02088 V$E2A_Q6_01.
MX M07353 V$E2A_Q6_02.
MX M00002 V$E47_01.
MX M00071 V$E47_02.
MX M01034 V$EBOX_Q6_01.
MX M00222 V$HAND1E47_01.
MX M00929 V$MYOD_Q6_01.
MX M00066 V$TAL1ALPHAE47_01.
MX M00065 V$TAL1BETAE47_01.
XX
BS R04244.
BS R03109.
BS R02139.
BS R04467.
BS R32066.
BS R04046.
BS R16617.
BS R18521.
BS R18522.
BS R03471.
BS R04418.
BS R00881.
BS R00882.
BS R00883.
BS R00240.
BS R00241.
BS R00242.
BS R02898.
BS R03074.
BS R08512.
XX
DR TRANSPATH: MO000024771.
DR EMBL: M24405;
DR EMBL: M31523;
DR UniProtKB: P15923-1;
XX
RN [1]; RE0000053.
RX PUBMED: 2503252.
RA Murre C., McCaw P. S., Vaessin H., Caudy M., Jan L. Y., Jan Y. N., Cabrera C. V., Buskin J. N., Hauschka S. D., Lassar A. B., Weintraub H., Baltimore D.
RT Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence
RL Cell 58:537-544 (1989).
RN [2]; RE0000055.
RX PUBMED: 2156629.
RA Benezra R., Davis R. L., Lockshon D., Turner D. L., Weintraub H.
RT The protein Id: a negative regulator of helix-loop-helix DNA binding proteins
RL Cell 61:49-59 (1990).
RN [3]; RE0000092.
RX PUBMED: 2493990.
RA Murre C., McCaw P. S., Baltimore D.
RT A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins
RL Cell 56:777-783 (1989).
RN [4]; RE0000161.
RX PUBMED: 1967982.
RA Nourse J., Mellentin J. D., Galili N., Wilkinson J., Stanbridge E., Smith S. D., Cleary M. L.
RT Chromosomal translocation t(1;19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor
RL Cell 60:535-545 (1990).
RN [5]; RE0000231.
RX PUBMED: 1846322.
RA Sun X.-H., Baltimore D.
RT An inhibitory domain of E12 transcription factor prevents DNA binding in E12 homodimers but not in E12 heterodimers
RL Cell 64:459-470 (1991).
RN [6]; RE0000661.
RX PUBMED: 2200736.
RA Nelson C., Shen L.-P., Meister A., Fodor E., Rutter W. J.
RT Pan: a transcriptional regulator that binds chymotrypsin, insulin, and AP-4 enhancer motifs
RL Genes Dev. 4:1035-1043 (1990).
RN [7]; RE0000670.
RX PUBMED: 1899229.
RA Ruezinsky D., Beckmann H., Kadesh T.
RT Modulation of the Igh enhancer's cell type through a genetic switch
RL Genes Dev. 5:29-37 (1991).
RN [8]; RE0000671.
RX PUBMED: 1672117.
RA Kamps M. P., Look A. T., Baltimore D.
RT The human t(1;19) translocation in pre-B ALL produces multiple nuclear E2A-Pbx1 fusion proteins with differing transforming potentials
RL Genes Dev. 5:358-368 (1991).
RN [9]; RE0000672.
RX PUBMED: 1714414.
RA Schlissel M., Voronova A., Baltimore D.
RT Helix-loop-helix transcription factor E47 activates germ-line immunoglobulin heavy-chain gene transcription and rearrangement in a pre-T-cell line
RL Genes Dev. 5:1367-1376 (1991).
RN [10]; RE0000968.
RX PUBMED: 1847137.
RA Chakraborty T., Brennan T., Olson E.
RT Differential trans-activation of a muscle-specific enhancer by myogenic helix-loop-helix proteins is separable from DNA binding
RL J. Biol. Chem. 266:2878-2882 (1991).
RN [11]; RE0001469.
RX PUBMED: 1990271.
RA Murre C., Voronova A., Baltimore D.
RT B-cell- and myocyte-specific E2-box-binding factors contain E12/E47-like subunits
RL Mol. Cell. Biol. 11:1156-1160 (1991).
RN [12]; RE0001620.
RX PUBMED: 1850096.
RA French B. A., Chow K.-L., Olson E. N., Schwartz R. J.
RT Heterodimers of myogenic helix-loop-helix regulatory factors and E12 bind a complex element governing myogenic induction of the avian cardiac alpha-actin promoter
RL Mol. Cell. Biol. 11:2439-2450 (1991).
RN [13]; RE0001651.
RX PUBMED: 1646392.
RA Chakraborty T., Brennan T. J., Li L., Edmondson D., Olson E. N.
RT Inefficient homooligomerization contributes to the dependence of myogenin on E2A products for efficient DNA binding
RL Mol. Cell. Biol. 11:3633-3641 (1991).
RN [14]; RE0002932.
RX PUBMED: 8289805.
RA Hsu H.-L., Huang L., Tsan J. T., Funk W., Wright W. E., Hu J.-S., Kingston R. E., Baer R.
RT Preferred sequences for DNA recognition by the TAL1 helix-loop-helix proteins
RL Mol. Cell. Biol. 14:1256-1265 (1994).
RN [15]; RE0003087.
RX PUBMED: 1312219.
RA Hu J.-S., Olson E. N., Kingston R. E.
RT HEB, a helix-loop-helix protein related to E2A and ITF2 that can modulate the DNA-binding ability of myogenic regulatory factors
RL Mol. Cell. Biol. 12:1031-1042 (1992).
RN [16]; RE0003235.
RX PUBMED: 8253390.
RA Shirakata M., Friedman F. K., Wei Q., Paterson B. M.
RT Dimerization specificity of myogenic helix-loop-helix DNA-binding factors directed by nonconserved hydrophilic residues
RL Genes Dev. 7:2456-2470 (1993).
RN [17]; RE0003408.
RX PUBMED: 1325437.
RA Chakraborty T., Martin J. F., Olson E. N.
RT Analysis of the oligomerization of myogenin and E2A products in vivo using a two-hybrid assay system
RL J. Biol. Chem. 267:17498-17501 (1992).
RN [18]; RE0003542.
RX PUBMED: 8497267.
RA Bain G., Gruenwald S., Murre C.
RT E2A and E2-2 are subunits of B-cell-specific E2-box DNA-binding proteins
RL Mol. Cell. Biol. 13:3522-3529 (1993).
RN [19]; RE0003543.
RX PUBMED: 8423802.
RA Quong M. W., Massari M. E., Zwart R., Murre C.
RT A new transcriptional-activation motif restricted to a class of helix-loop-helix proteins is functionally conserved in both yeast and mammalian cells
RL Mol. Cell. Biol. 13:792-800 (1993).
RN [20]; RE0003728.
RX PUBMED: 8355705.
RA Sawada S., Littman D. R.
RT A heterodimer of HEB and an E12-related protein interacts with the CD4 enhancer and regulates its activity in T-cell lines
RL Mol. Cell. Biol. 13:5620-5628 (1993).
RN [21]; RE0004014.
RX PUBMED: 1967983.
RA Kamps M. P., Murre C., Sun X. H., Baltimore D.
RT A new homeobox gene contributes the DNA binding domain oft the t(1; 19) translocation protein in pre-B ALL
RL Cell 60:547-555 (1990).
RN [22]; RE0004016.
RX PUBMED: 2799390.
RA Mellentin J. D., Murre C., Donlon T. A., McCaw P. S., Smith S. D., Carroll A. J., McDonald M. E., Baltimore D., Cleary M. L.
RT The gene for enhancer binding proteins E12/E47 lies at the t(1;19) breakpoint in acute leukemias
RL Science 246:379-382 (1989).
RN [23]; RE0004018.
RX PUBMED: 8093327.
RA Kamps M. P., Baltimore D.
RT E2A-Pbx1, the t(1;19) translocation protein of human pre-B-cell acute lymphocytic leukemia causes acute myeloid leukemia in mice
RL Mol. Cell. Biol. 13:351-357 (1993).
RN [24]; RE0004019.
RX PUBMED: 8383120.
RA Staudinger J., Perry M., Elledge S. J., Olson E. N.
RT Interactions among vertebrate helix-loop-helix proteins in yeast using the two-hybrid system
RL J. Biol. Chem. 268:4608-4611 (1993).
RN [25]; RE0004020.
RX PUBMED: 7925274.
RA Peverali F. A., Ramqvist T., Saffrich R., Pepperkok R., Barone M. V., Philipson L.
RT Regulation of G1 progression by E2A and Id helix-loop-helix proteins
RL EMBO J. 13:4291-4301 (1994).
RN [26]; RE0004021.
RX PUBMED: 8001133.
RA Benezra R.
RT An intermolecular disulfide bond stabilizes E2A homodimers and is required for DNA binding at physiological temperatures
RL Cell 79:1057-1067 (1994).
RN [27]; RE0005180.
RX PUBMED: 8104101.
RA Dedera D. A., Waller E. K., LeBrun D. P., Sen-Majumdar A., Stevens M. E., Barsh G. S., Cleary M. L.
RT Chimeric homeobox gene E2A-PBX1 induces proliferation, apoptosis, and malignant lymphomas in transgenic mice
RL Cell 74:833-843 (1993).
RN [28]; RE0005830.
RX PUBMED: 7862133.
RA Robinson G. L. W. G., Henderson E., Massari M. E., Murre C., Stein R.
RT c-Jun inhibits insulin control element-mediated transcription by affecting the transactivation potential of the E2A gene products
RL Mol. Cell. Biol. 15:1398-1404 (1995).
RN [29]; RE0006798.
RX PUBMED: 7589808.
RA Li L., Cserjesi P., Olson E. N.
RT Dermo-1: A novel twist-related bHLH protein expressed in the developing dermis
RL Dev. Biol. 172:280-292 (1995).
RN [30]; RE0010487.
RX PUBMED: 7739551.
RA Naidu P. S., Ludolph D. C., To R. Q., Hinterberger T. J., Konieczny S. F.
RT Myogenin and MEF2 function synergistically to activate the MRF4 promoter during myogenesis
RL Mol. Cell. Biol. 15:2707-2718 (1995).
RN [31]; RE0012509.
RX PUBMED: 8759016.
RA Loveys D. A., Streiff M. B., Kato G. J.
RT E2A basic-helix-loop-helix transcription factors are negatively regulated by serum growth factors and by the ld3 protein
RL Nucleic Acids Res. 24:2813-2820 (1996).
RN [32]; RE0012731.
RX PUBMED: 8628307.
RA Miyamoto A., Cui X., Naumovski L., Cleary M. L.
RT Helix-loop-helix proteins LYL1 and E2a form heterodimeric complexes with distinctive DNA-binding properties in hematolymphoid cells
RL Mol. Cell. Biol. 16:2394-2401 (1996).
RN [33]; RE0039511.
RX PUBMED: 9235903.
RA Anand G., Yin X., Shahidi A. K., Grove L., Prochownik E. V.
RT Novel regulation of the helix-loop-helix protein Id1 by S5a, a subunit of the 26 S proteasome
RL J. Biol. Chem. 272:19140-51 (1997).
RN [34]; RE0047866.
RX PUBMED: 16135793.
RA Kawai-Kowase K., Kumar M. S., Hoofnagle M. H., Yoshida T., Owens G. K.
RT PIAS1 activates the expression of smooth muscle cell differentiation marker genes by interacting with serum response factor and class I basic helix-loop-helix proteins.
RL Mol. Cell. Biol. 25:8009-8023 (2005).
RN [35]; RE0048930.
RX PUBMED: 10749989.
RA el Ghouzzi V., Legeai-Mallet L., Aresta S., Benoist C., Munnich A., De Gunzburg J., Bonaventure J.
RT Saethre-Chotzen mutations cause TWIST protein degradation or impaired nuclear location.
RL Hum. Mol. Genet. 9:813-819 (2000).
RN [36]; RE0048980.
RX PUBMED: 9242638.
RA Langlands K., Yin X., Anand G., Prochownik E. V.
RT Differential interactions of Id proteins with basic-helix-loop-helix transcription factors.
RL J. Biol. Chem. 272:19785-19793 (1997).
RN [37]; RE0049099.
RX PUBMED: 10502414.
RA Law S. F., Zhang Y. Z., Fashena S. J., Toby G., Estojak J., Golemis E. A.
RT Dimerization of the docking/adaptor protein HEF1 via a carboxy-terminal helix-loop-helix domain.
RL Exp. Cell Res. 252:224-235 (1999).
XX
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